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https://f1000research.com/articles/13-183/v1
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11 Mar 24
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{
"type": "Research Article",
"title": "Presentations and Incidence of Ocular Injuries Caused by Motorcycle Accidents in Iraq",
"authors": [
"Zainab A. Hashim",
"Suzan K. Mohammed",
"Marwan Y. Abdulla",
"Hayder A Fawzi",
"Zainab A. Hashim",
"Suzan K. Mohammed",
"Marwan Y. Abdulla"
],
"abstract": "Background Motorcycle accidents can be particularly hazardous, as riders are exposed to various risk factors, such as high speeds, lack of protective enclosures, and limited safety features.\n\nAim of the study To describe the ocular injuries associated with motorcycled accidents presented to a tertiary center in Iraq.\n\nPatients and methods A multicenter cross-sectional (survey) study that involved 335 cases of motorcycle accidents that presented with unilateral or bilateral ocular trauma. The study was carried out at Ibn Al-Haitham Teaching Hospital, Al-Nauman Teaching Hospital, Al-Diwaniyah Teaching Hospital, and forensic centers located in Baghdad (Iraq capital) and Al-Qadisiyah from 1st of June 2019 to 1st of June 2023. Information regarding ocular injuries was recorded and classified according to the International Ocular Trauma Classification.\n\nResults The study involved 335 ophthalmological accidents; the mean age of the patients was 27.84± 9.6 years, most of them were males (96.7%), and there were only 11 females as passengers, 39 (11.6%) had injuries in both eyes. Lesions involving the periorbita, lids, and conjunctiva comprised most of the findings. There were 60.9% of patients with lid lacerations with or without sub-conjunctival bleeding, 22.1% with corneoscleral injury, and 17.9% with commotio retinae. It was the leading cause of decreased visual acuity, with 9% having lens capsule damage with or without iris prolapse and 8.1% having a ruptured capsule, 55.82% of patients had a mild injury, 27.16% had a moderate injury, and 17.01% had a severe injury.\n\nConclusion Eye injury associated with motorcycle accidents mainly affect males in their youth age and has serious outcomes, sometimes ending with blindness.",
"keywords": [
"Motorcycles",
"Accidents",
"Eye Injuries",
"Visual Acuity"
],
"content": "Introduction\n\nMillions of injuries occur worldwide as a result of road traffic accidents, making them the primary cause of death in adolescents and adults across the world.1 Motorcycle-related accidents, in particular, pose a significantly higher risk of injury than other types of road traffic accidents.2 In the American Academy of Ophthalmology, there is an annual occurrence of 2.5 million eye injuries in the United States, with around 50,000 individuals experiencing either partial or complete loss of vision.1,3\n\nWhile a relatively small proportion of eye injuries contribute to these statistics through motorcycle accidents, it is important to recognize that eye injuries and vision loss can occur as a result of motorcycle crashes.4 Therefore, it is strongly advised that both motorcyclists and their passengers consistently wear appropriate eye protection whenever they ride their bikes.5 Recent data from the United States indicates a 10.5% rise in such incidents in 2021 compared to 2020.6 The problem of motorcycle injuries and fatalities has a greater impact on individuals from lower and middle socioeconomic classes, primarily due to motorcycles being a common mode of transportation in developing countries and to a lesser extent in developed nations.7,8\n\nThe lack of strict enforcement of licensing regulations has created opportunities for individuals to obtain licenses without undergoing required eye tests or demonstrating riding proficiency.9,10 Consequently, many motorcycle riders are unfamiliar with the rules and regulations outlined in the Highway Code in Iraq.11 This has led to a high occurrence of accidents involving motor vehicles and motorcyclists, collisions between motorcyclists and pedestrians, and even among motorcyclists themselves. Intraocular injuries can be categorized into two types: closed globe injuries, which involve partial-thickness wounds in the wall of the eyeball12 and can be further classified as contusions or lamellar lacerations,13 and open globe injuries, which involve full-thickness wounds in the eyeball wall, such as ruptures caused by blunt trauma,12 lacerations, penetrating or perforating injuries, or injuries involving intraocular foreign bodies resulting from sharp forces.14 Adnexal injuries, on the other hand, pertain to injuries affecting the eyelid and/or conjunctiva.15\n\nOcular trauma imposes a substantial burden on ophthalmic services, constituting 38-52% of all new patients seeking emergency care at hospitals due to accidents.15–17 There is a limited amount of literature available regarding ocular injuries specifically related to motorcycle-related trauma. Enock et al. conducted a study involving 56 eyes with ocular injuries, and it was found that none of the patients were wearing helmets at the time of the injury.18 Ocular trauma has the potential to cause significant and irreversible visual impairment due to the intricate and delicate structure of the eye. Ocular traumas are known to be the leading cause of monocular low vision and blindness.19 The objective of the current study is to highlight the most common types of ocular injuries resulting from motorcycle accidents in Iraq, focusing on the severity of these injuries and their impact on visual outcomes.\n\n\nMethods\n\nIn a multicenter cross-sectional (survey) study that involved 335 cases of motorcycle accidents that presented with unilateral or bilateral ocular trauma. Consent was obtained from the patients to participate in the study, and information on the age, sex, laterality, type of ocular injury, ocular findings, severity of the lesion, and visual acuity were recorded, these information regarding ocular injuries were recorded and classified according to the International Ocular Trauma Classification used in previous studies for the classification of ocular traumas according to visual acuity, pupillary light response, zone and type of injury, each given a score as illustrated by Dahal and Byenju (2013).20\n\nThe study was carried out at Ibn Al-Haitham Teaching Hospital, Al-Nauman Teaching Hospital, Al-Diwaniyah Teaching Hospital, and forensic centers located in Baghdad (Iraq capital) and Al-Qadisiyah from 1st of June 2019 to 1st of June 2023. Written consent was obtained from the patients if they were fully oriented or from their caregivers (for participants aged below 18 since they are considered children in Iraq), after providing an adequate explanation of the aims and methods of the study.\n\nInclusion criteria\n\nPatients of all ages and both sexes are presented with ocular injuries during motorcycle accidents.\n\nExclusion criteria\n\nPatients who refused to participate in the study.\n\nThis study was approved by the Research Ethics Committee in Al-Qadisiyah University/College of Medicine. (Approval no.: 25/285, on 22nd of May 2019). Written consent was obtained from the patients if they were over 18 years old or from their caregivers, after providing adequate explanation of the aims and methods of the study.\n\nSample size estimation was based on the following equation:\n\nWhere n is the minimum sample size, p is the prevalence of ocular trauma was 13.5% based on a previous study21 among patients admitted to the trauma unit. The Z represents the Z-score at 95 % confidence interval, and it equals 1.96, d represents the marginal error which is accepted according to Ref. 22 to be 0.04. Thus, the minimum sample size was estimated to be approximately 280.\n\nDescriptive statistics were used that included frequency and percentage; GraphPad Prism version 10 was used for the analysis.\n\n\nResults\n\nThe mean age of the patients was 27.84± 9.6 years, most of them were males (96.7%), and there were only 11 females as passengers, 39 (11.6%) had injuries in both eyes, as shown in Table 1.\n\n* The involvement of females was as passengers.\n\nLesions involving the periorbita, lids, and conjunctiva comprised the majority of the findings. There were 60.9% of patients with lid laceration ± sub-conjunctival hemorrhage, 22.1% with corneoscleral injury, 17.9% with commotio retinae and it was the leading cause of decreased visual acuity, 9% with lens capsule damage ± iris prolapse, and 8.1% with ruptured capsule, as shown in Table 2.\n\n* This grouping concentrates on the presenting and most severe injury.\n\nAfter applying the International Ocular Trauma Classification system, 55.82% of patients had a mild injury, 27.16% had a moderate injury and 17.01% had a severe injury, as shown in Table 3.\n\nThe visual acuity of the participants ranged from 6/6 to no light perception, 59.1% of patients had visual acuity better than 6/18, 29.0% from 6/18 to 6/60, 8.1% from 6/60 to counting fingers, and 3.9% with no light perception, as shown in Table 4.\n\n\nDiscussion\n\nOcular injuries resulting from motorcycle accidents can range from mild to severe and can have lasting effects on vision; motorcycle accidents often expose riders to various types of impact debris and forces that can directly or indirectly lead to ocular injuries.4\n\nThe age and sex distribution in the current study were in agreement with the results of Larona and Pe-Yan (2012), as they studied 34 cases of motorcycle ocular injuries and reported a mean of 27.1 years, and 88.2% of their study sample was composed of males.23 Hsieh et al. (2017) reported that 6,072 were admitted due to motorcycle injuries, 994 (16.4%) of them were ≥ 65 years, and 5078 (83.6%) were aged between 20-64 years; however, females formed 41.9% of the elderly and 42.9% of adults.24 These findings offer a much higher rate of injury in females; the lower rate of females injured in the current study could be attributed to cultural hindrances posed by society, which limit females as the primary drivers of vehicles. Social/cultural factors play a significant role in the age and sex distribution of motorcycle riders, as in Taiwan it is very common for females to ride bikes,25 and in another study done by the same author, female riders formed 42.01% of the study sample and were younger, passengers more than riders, used helmets more than males, and had different injury characteristics and lower in-hospital mortality in comparison to males.25\n\nIn the current study, patient injuries included lid lacerations and sub-conjunctival hemorrhage, corneoscleral injury, commotio retinae, lens capsule damage ± iris prolapse, ruptured capsule, and orbital blowout fractures. Soft tissue injuries were the most prevalent probably because of the very limited use of helmets in our country. None of the current studies reported using helmets regularly, Arif et al. (2019) reported that although facial soft tissue injuries occur in helmeted riders, it occurs far more in non-helmeted ones.26 To the best of our knowledge, no study directly reported open globe injury due to motorcycle injury, rather aggregated road traffic accidents cases, Upaphong et al. (2021) reported that motorcycle injuries constituted 56.3% of patients aged <20 years, 25% (age 20-39 years), 15% (aged 40-59 years), and 20% (age >60 years), and in all patients, hyphema were seen in 55.4%, lens injuries (52.5%), and uveal prolapse (55.4%).27 In a review done by Kim et al. (2022) it was reported that blowout fractures were the third observed mechanism for orbital fractures,28 Also other studies reported that motorcycle accidents were the leading cause of orbital/facial fractures.29,30\n\nDirect contact between the eye and a chemical (e.g., gasoline), or even chemical fumes, can cause burns.31 Sources of radiation, such as bright ultra violet (UV) headlights, can also cause a flash burn.32 Other drivers may be injured because of their reckless driving and collision with other cars and heavy objects on the side road.33 Driving under the influence of alcohol can lead to accidents, which not only affects the driver but also the passengers and other people on the road.34\n\nSince only two governates out of 18 limit the conclusion, at the same time, it gives us an initial assessment of the seriousness of the ocular injuries, a national study that involves most of the country is necessary.\n\n\nConclusion\n\nIn summary, the analysis of eye injuries associated with motorcycle accidents highlights a significant concern primarily affecting young males. The outcomes of these incidents can be particularly severe, at times resulting in permanent blindness. Policymakers, traffic safety authorities, and healthcare professionals must address this issue with targeted interventions and awareness campaigns. By emphasizing the importance of proper protective gear, safe riding practices, and education, we can work towards reducing the occurrence of such injuries and minimizing their life-altering consequences. Furthermore, fostering a culture of responsible riding and enhancing road infrastructure can contribute to safer roads for all, ultimately preventing these devastating eye injuries and their far-reaching impacts on individuals and society as a whole.",
"appendix": "Data availability\n\nZenodo: Ocular Injuries Caused by Motorcycle Accidents [Data set]. https://doi.org/10.5281/zenodo.8370156. 35\n\nThe project contains the following underlying data:\n\n- Data sets of Ocular Injuries Caused by Motorcycle Accidents.\n\nZenodo: Ocular Injuries Caused by Motorcycle Accidents. https://doi.org/10.5281/zenodo.8370208. 36\n\nThe project contains the following underlying data:\n\n- STROBE 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\nKortor JN, Yinusa W, Ugbeye ME: Lower limb injuries arising from motorcycle crashes. Niger J Med. 2010; 19(4): 475–478. PubMed Abstract | Publisher Full Text\n\nMeena S, Rakheja V, Sahu S, et al.: Traumatic avulsion of the globe with optic nerve transection: an unusual presentation. BMJ Case Rep. 2020; 13(10). Publisher Full Text\n\nOkamoto Y, Morikawa S, Okamoto F, et al.: Traffic Accident-Related Open Globe Injuries. Retina. 2019; 39(4): 779–785. PubMed Abstract | Publisher Full Text\n\nKim EJ, Ganga A, Kang C, et al.: Motorcycle-Associated Ocular Injuries: A Narrative Review. Clin Ophthalmol. 2022; 16: 3457–3479. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAhmad S: Knowledge, attitude and compliance with safety protective devices among commercial motorcyclists in Tudun-Wada Zaria, North-Western Nigeria. Ann Niger Med. 2012; 6(2): 80. Publisher Full Text\n\nNational Highway Traffic Safety Administration: Newly Released Estimates Show Traffic Fatalities Reached a 16-Year High in 2021. Washington, DC: United States Department of Transportation; 2022 [cited 2022 May, 5]. Reference Source\n\nBittar CK, Cliquet A, Costa V, et al.: SOCIOECONOMIC IMPACT OF MOTORCYCLE ACCIDENT VICTIMS IN THE EMERGENCY ROOM OF A HOSPITAL (PART 2). Acta Ortop Bras. 2020; 28(3): 149–151. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMartins ET, Boing AF, Peres MA: Mortalidade por acidentes de motocicleta no Brasil: análise de tendência temporal, 1996-2009. Rev Saude Publica. 2013; 47: 931–941. PubMed Abstract | Publisher Full Text\n\nAlam J, Bhattacharjya H, Roy A, et al.: Epidemiology and outcome of ocular trauma among the road traffic accident cases attending a tertiary care hospital in Tripura. Int J Med Sci Public Health. 2014; 3(4): 422–424. Publisher Full Text\n\nOtte D, Willeke H, Chinn B, et al., editors. Impact mechanisms of helmet protected heads in motorcycle accidents-accidental study of COST 327. International Motorcycle Conference; 1989 1998.\n\nWaleed M, Abdul-Sahib M, Al-Ghabban SI: Risk Factors and Pattern of Injuries in Motorcycle Accidents in Holy Karbala. Karbala J Med. 2013; 6(1): 1552–1560.\n\nKumar K, Figurasin R, Kumar S, et al.: An Uncommon Meridional Globe Rupture due to Blunt Eye Trauma. Case Rep Emerg Med. 2018; 2018: 1–3. Publisher Full Text\n\nAl-Thowaibi A, Kumar M, Al-Matani I: An overview of penetrating ocular trauma with retained intraocular foreign body. Saudi J Ophthalmol. 2011; 25(2): 203–205. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMutie D, Mwangi N: Assessing an eye injury patient. Community Eye Health. 2015; 28(91): 46–48. PubMed Abstract\n\nIoannidis AS, Tranos PG, Harris M: Valsalva retinopathy associated with riding a motorcycle. Eye (Lond.). 2004; 18(3): 329–331. PubMed Abstract | Publisher Full Text\n\nBureau of Transportation Statistics: Motorcycle Trends in the United States. United States: Research and Innovative Technology Administration; May, 2009.\n\nAdeleye AO, Ogun MI: Clinical epidemiology of head injury from road-traffic trauma in a developing country in the current era. Front Neurol. 2017; 8: 695. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEnock ME, Omoti AE, Alikah AA: Risk factors identification for ocular trauma in patients who presented in a suburban tertiary care hospital in Nigeria. Saudi Med J. 2007; 28(9): 1385–1388. PubMed Abstract\n\nPriyadarshini N, Vaibhav V, Singh UN: An Observational Cross-Sectional Determination of the Epidemiology and Type of Ocular Injuries that Resulted from Motorcycle Accidents. Int J Pharm Clin Res. 2021; 13(6): 793–797.\n\nDahal P, Byenju R: Evaluation of surgical outcome in open globe injuries in a tertiary ophthalmological centre. J Coll Med Sci Nepal. 2013; 9(2): 9–14. Publisher Full Text\n\nSastry SM, Paul BK, Bain L, et al.: Ocular trauma among major trauma victims in a regional trauma center. J. Trauma. 1993; 34(2): 223–226. Publisher Full Text\n\nDaniel WW, Cross CL: Biostatistics: a foundation for analysis in the health sciences. Wiley; 2018.\n\nLarona AJL, Pe-Yan MRL: Visual profile of motorcycle-related Ocular trauma in a tertiary hospital. Philipp J Ophthalmol. 2012; 37(2): 111–116.\n\nHsieh C-H, Liu H-T, Hsu S-Y, et al.: Motorcycle-related hospitalizations of the elderly. Biom J. 2017; 40(2): 121–128.\n\nHsieh C-H, Hsu S-Y, Hsieh H-Y, et al.: Differences between the sexes in motorcycle-related injuries and fatalities at a Taiwanese level I trauma center. Biom J. 2017; 40(2): 113–120.\n\nArif MZ, Rajanikanth BR, Prasad K: Soft tissue injuries of the maxillofacial region occurring from motorcycle accidents. J Maxillofac Oral Surg. 2019; 18: 432–439. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUpaphong P, Supreeyathitikul P, Choovuthayakorn J: Open Globe Injuries Related to Traffic Accidents: A Retrospective Study. J. Ophthalmol. 2021; 2021: 6629589.\n\nKim EJ, Ganga A, Kang C, et al.: Motorcycle-associated ocular injuries: a narrative review. Clin Ophthalmol. 2022; 16: 3457–3479. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCalderoni DR, de Campos GM , Kharmandayan P, et al.: Seven-year institutional experience in the surgical treatment of orbito-zygomatic fractures. J Craniofac Surg. 2011; 39(8): 593–599.\n\nManana W, Odhiambo WA, Chindia ML, et al.: The pattern of orbital fractures managed at two referral centers in Nairobi, Kenya. J Craniofac Surg. 2017; 28(4): e338–e342. PubMed Abstract | Publisher Full Text\n\nHurt HH, Ouellet JV, Thom DR: Motorcycle accident cause factors and identification of countermeasures. United States: National Highway Traffic Safety Administration; 1981; vol. 1. . technical report.\n\nSliney DH: Photoprotection of the eye – UV radiation and sunglasses. J Photochem Photobiol B Biol. 2001; 64(2): 166–175. PubMed Abstract | Publisher Full Text\n\nLin C-H, Wang C-Y, Shen Y-C, et al.: Clinical characteristics, intraoperative findings, and surgical outcomes of canalicular laceration repair with monocanalicular stent in Asia. J Ophthalmol. 2019; 2019: 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLev Ari O, Shaked G, Michael T, et al.: Ocular injuries associated with two-wheeled electric transportation devices and motorcycle accidents. Sci Rep. 2022; 12(1): 20546. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFawzi HA: Ocular Injuries Caused by Motorcycle Accidents. [Data set]. Zenodo. 2023. Publisher Full Text\n\nFawzi HA: Ocular Injuries Caused by Motorcycle Accidents. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "267248",
"date": "10 May 2024",
"name": "Japheths Ogendi",
"expertise": [
"Reviewer Expertise My areas of research are in Epidemiology with emphasis on Epidemiology of NCDs and road traffic injuries."
],
"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 gone through the work. This is an important study that touches on a major public health concern, ocular injuries. However, the study needs to be revised and additional information added to it to make it complete. For example, the background of the study needs to be revised to improve on its readability. I have provided details in track changes which can be viewed in the file linked here.\nThe Section on Methods needs to be reexamined. For example, the authors should make it clear to readers, who may not be familiar with the study settings, sufficient geographical to introduce the study sites. Many readers may not be familiar with Iraq or the teaching hospitals and forensic centers. Equally important is to add the reasons why the teaching hospitals and forensic centers were chosen. (I have included an example of a study that has shown how to do this in a reference indicated in track changes). It should also be made clear where exactly the study participants were gotten, were they Emergency Departments? The authors should consider revising the findings and present them according to conventions of reporting scientific findings. The findings reported in this study started presenting ages and sex. It would be important for the readers to know the denominator, the total number of participants then proceed to present the distribution different categories .\nThe authors should strive to improve the discussion section by focusing the discussion on how the major findings of the study relates with other findings in previous studies. This has not been adequately achieved. The public health implication of the study findings and the implication of the findings to practice and policy should be addressed where possible. Consider also revising the study limitations and draw three or four from study design, settings or data collection instruments. The work is a good effort but it can still be improved. I have also taken an effort to be more clear by adding proposed suggestions in track changes. If this is required Ill provide it. I think it has captured lots of details as well.\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? Yes",
"responses": [
{
"c_id": "12236",
"date": "30 Aug 2024",
"name": "Hayder A Fawzi",
"role": "Author Response",
"response": "Dear Reviewer, Reviewer Comments - I have gone through the work. This is an important study that touches on a major public health concern, ocular injuries. However, the study needs to be revised and additional information added to it to make it complete. For example, the background of the study needs to be revised to improve on its readability. I have provided details in track changes which can be viewed in the file linked Reviewer Notes from Tracked file - 1/ The reference needs to be counterchecked. The authors talk of the American Academy of Ophthalmology that has an annual occurrence of 2.5 million eye injuries. However, the references appear to be from other sources, not the academy. Kindly countercheck and update appropriately. Author response Reference 3 was counterchecked, and it was inappropriately placed; below is the correct reference: American Academy of Ophthalmology and American Society of Ocular Trauma, United States Eye Injury Registry summary report, 1998–2002. Available at: http://www.aao.org/newsroom/guide/upload/Eye-Injuries-BkgrnderLongVersFinal-l.pdf Reviewer Notes from Tracked file - 2/ Also consider revising the sentence. Do the authors mean , for example, or could consider this kind of wordings: “ According to the America Academy of Ophthalmology, a total of 2.5 million eye injuries are reported/occur in USA annually, with 50,000 individuals experiencing either partial or complete loss of vision” (American Academy of Ophthalmology Report, 20..) Author response We agree with the reviewer; the entire sentence lacks clarity; as such, we rephrase it to the following: According to the American Academy of Ophthalmology, 2.5 million eye injuries are reported/occur in the USA annually, with 50,000 individuals experiencing either partial or complete loss of vision. Reviewer Notes fromTracked file - 3/Regarding the number of previous studies on motorcycle accidents in Iraq, Author response This is the first study to examine motorcycle ocular injury in Iraq; as such, no previous study can be reported. We used estimated facts from developing countries to reflect the numbers. Reviewer Comments - 4/ The Section on Methods needs to be reexamined. For example, the authors should make it clear to readers, who may not be familiar with the study settings, sufficient geographical to introduce the study sites. Many readers may not be familiar with Iraq or the teaching hospitals and forensic centers. Equally important is to add the reasons why the teaching hospitals and forensic centers were chosen. (I have included an example of a study that has shown how to do this in a reference indicated in track changes). Author response We agree with the review suggestion; we included more details regarding the requested information as mentioned below: 2.1 Study design This study presented motorcycle accident injuries patients to the Emergency Department from June 1, 2019, to June 1, 2023. After admission, patients were screened to identify the motorcycle injuries that presented ocular trauma; for those identified to have ocular trauma, written consent was sought and obtained from the patients to participate in the study. Information was obtained from the injured patients, whether they were stable enough or from those who accompanied them for care. Written consent was obtained from the patients if they were over 18 years old or from their caregivers after providing an adequate explanation of the aims and methods of the study. Further information was gathered on the age, sex, laterality, type of ocular injury, ocular findings, lesion severity, and visual acuity. The information regarding ocular injuries was classified and recorded according to the International Ocular Trauma Classification 20. Previous studies have used this classification and scoring method to classify ocular traumas according to visual acuity, pupillary light response, zone, and type of injury. 2.2 Study settings According to the World Health Organization (WHO), Iraq's healthcare system has 2,652 facilities, of which 61 are teaching hospitals. This study was conducted in two governorates (Baghdad, the Iraqi capital, and Al-Qadisiyah), a total of three teaching hospitals: Ibn Al-Haitham Teaching Hospital (in Baghdad), Al-Nauman Teaching Hospital (in Baghdad), and Al-Diwaniyah Teaching Hospital (in Al-Diwaniyah), and the three forensic centers associated with these hospitals. Patients were interviewed initially in the emergency department; if the ocular trauma related to motorcycle injuries were confirmed, the patient would be transferred to the ophthalmology department when the patient was managed and interviewed for the study. Ibn Al-Haitham Teaching Hospital is Iraq's primary and largest ophthalmology hospital. This hospital only receives patients with ophthalmological conditions. It has a large inpatient capacity (200 beds) and many operating rooms (16 Operating Rooms) for various ophthalmic procedures. Al-Nauman Teaching Hospital is one of the largest teaching hospitals in Baghdad, and it contains various departments, including emergency and ophthalmology departments. Finally, Al-Diwaniyah Teaching Hospital is the largest teaching hospital in the Al-Diwaniyah governorate, with large emergency and ophthalmology departments. Reviewer Comments - 5/ It should also be made clear where exactly the study participants were gotten, were they Emergency Departments? The authors should consider revising the findings and present them according to conventions of reporting scientific findings. The findings reported in this study started presenting ages and sex. It would be important for the readers to know the denominator, the total number of participants then proceed to present the distribution different categories . Author response The answer to this question is provided in the previous question. Reviewer Comments - 6/ The authors should strive to improve the discussion section by focusing the discussion on how the major findings of the study relates with other findings in previous studies. This has not been adequately achieved. The public health implication of the study findings and the implication of the findings to practice and policy should be addressed where possible. Consider also revising the study limitations and draw three or four from study design, settings or data collection instruments. The work is a good effort but it can still be improved. Author response We improved both the results and the discussion accordingly. Abstract The study was conducted in three Teaching hospitals and forensic centers in Baghdad and Al-Qadisiyah in Iraq. Information regarding ocular injuries, recorded and classified according to the International Ocular Trauma Classification, was gathered from motorcycle crash injuries that were presented to the emergency departments of these facilities from June 1, 2019, to June 1, 2023. Results During the four years of the study, 6,243 patients presented with motorcycle injuries in the three Teaching hospitals and their forensic centers. Of those (5.37%), 335 patients were identified to have ocular trauma from the road crash. Table 1 presents the characteristics of motorcycle crash cases with ocular trauma. The ages of those with ocular trauma ranged from 10 to 67 years old, with a mean age of 27.84± 9.6 years. Most of them were 324 (96.7%) males, with a male-to-female ratio of 29 to 1, and there were only 11 females as passengers; 39 (11.6%) had injuries in both eyes, as shown in Table 1. Regarding the type of eye lesions during their presentation, there were 60.9% of patients with lid laceration with or without sub-conjunctival hemorrhage, 22.1% with corneoscleral injury, 17.9% with commotio retinae, and it was the leading cause of decreased visual acuity, 9% with lens capsule damage with or without iris prolapse, and 8.1% with ruptured capsule, as shown in Table 2. Reviewer Comments - 7/ I have also taken an effort to be more clear by adding proposed suggestions in track changes. If this is required Ill provide it. I think it has captured lots of details as well. Author response I appreciate your help; your notes and corrections improved the work, and we changed the article accordingly. Best regards"
}
]
},
{
"id": "303232",
"date": "25 Jul 2024",
"name": "Debapriya Mukhopadhyay",
"expertise": [
"Reviewer Expertise Public Health",
"Healthcare Strategy",
"Healthcare Administration",
"Community Eye Health",
"Diabetes",
"Medical imaging",
"Ophthalmology",
"Optometry",
"Medical Investigations & research",
"Cell biology research"
],
"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\nWhat went well?\nThe comprehensive study conducted across multiple centres in Iraq provides valuable insights into the ocular injuries resulting from motorcycle accidents. The meticulous classification of injuries according to the International Ocular Trauma Classification has allowed for a detailed understanding of the types and severities of ocular trauma. The findings highlight the importance of protective gear and safety measures for motorcyclists, as the majority of injuries were to young males, indicating a demographic at high risk. The study's extensive data collection over four years offers a solid foundation for developing strategies to prevent such injuries and improve outcomes for those affected. It's a significant step towards enhancing road safety and healthcare protocols for ocular injuries in Iraq and potentially other regions with similar contexts.\nThe study gap\nThe study presents a significant contribution to understanding the ocular trauma associated with motorcycle accidents in Iraq, highlighting the prevalence of such injuries among young male riders. However, the research reveals gaps that warrant further investigation. The disproportionate representation of male patients could be indicative of cultural or behavioral patterns that influence motorcycle usage and risk exposure, suggesting a need for gender-specific safety interventions. Additionally, the study's focus on tertiary centers in urban areas may not capture the full spectrum of ocular injuries, particularly those treated in rural or non-hospital settings. The classification of injuries, while standardized, does not account for long-term outcomes or the socioeconomic impact on the patients. Future studies could benefit from a longitudinal approach, assessing the recovery trajectory and quality of life post-injury, as well as exploring preventive measures tailored to the local context. Moreover, integrating multidisciplinary perspectives, including ophthalmology, trauma surgery, and public health, could provide a more comprehensive understanding of the factors contributing to these injuries and the strategies needed to mitigate them.\nStatistical significance is missing in the results.\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? Yes",
"responses": [
{
"c_id": "12237",
"date": "23 Aug 2024",
"name": "Hayder A Fawzi",
"role": "Author Response",
"response": "Dear Reviewer, Reviewer Comments - What went well? The comprehensive study conducted across multiple centres in Iraq provides valuable insights into the ocular injuries resulting from motorcycle accidents. The meticulous classification of injuries according to the International Ocular Trauma Classification has allowed for a detailed understanding of the types and severities of ocular trauma. The findings highlight the importance of protective gear and safety measures for motorcyclists, as the majority of injuries were to young males, indicating a demographic at high risk. The study's extensive data collection over four years offers a solid foundation for developing strategies to prevent such injuries and improve outcomes for those affected. It's a significant step towards enhancing road safety and healthcare protocols for ocular injuries in Iraq and potentially other regions with similar contexts. The study gap 1/ The study presents a significant contribution to understanding the ocular trauma associated with motorcycle accidents in Iraq, highlighting the prevalence of such injuries among young male riders. However, the research reveals gaps that warrant further investigation. The disproportionate representation of male patients could be indicative of cultural or behavioral patterns that influence motorcycle usage and risk exposure, suggesting a need for gender-specific safety interventions. Author response We agree with the reviewer the high prevalence of ocular injuries in males is attributed to couturier factors, such as males representing the majority of the drivers in our country, and which will lead to a higher proportion of males inflicted with ocular injuries. Reviewer Comments - 2/ Additionally, the study's focus on tertiary centers in urban areas may not capture the full spectrum of ocular injuries, particularly those treated in rural or non-hospital settings. Author response We chose the largest hospitals in the country since other locations have low presentation of such access. We agree with the reviewer that there is a strong need to examine ocular injury in non-tertiary hospitals and other health care facilities. However, this is beyond the scope of the current study. Reviewer Comments - 3/ The classification of injuries, while standardized, does not account for long-term outcomes or the socioeconomic impact on the patients. Future studies could benefit from a longitudinal approach, assessing the recovery trajectory and quality of life post-injury, as well as exploring preventive measures tailored to the local context. Moreover, integrating multidisciplinary perspectives, including ophthalmology, trauma surgery, and public health, could provide a more comprehensive understanding of the factors contributing to these injuries and the strategies needed to mitigate them. Author response We agree with the reviewer that this work should be the basis of further studies in this direction. Reviewer Comments - 4/ Statistical significance is missing in the results. Author response This is a descriptive study; there is no comparison between the different groups, so no statistical analysis applies to the current work. Best regards"
}
]
}
] | 1
|
https://f1000research.com/articles/13-183
|
https://f1000research.com/articles/12-1464/v1
|
13 Nov 23
|
{
"type": "Research Article",
"title": "Lived experiences of women who survived from pre-eclampsia and eclampsia in public hospitals of Shashemene Town, Oromia Region, Ethiopia: a qualitative study.",
"authors": [
"Negeso Gebeyehu",
"Aman Urgessa",
"Daniel Yohannes",
"Aster Yalew",
"Muluneh Ahmed",
"Meron Admasu",
"Aman Urgessa",
"Daniel Yohannes",
"Aster Yalew",
"Muluneh Ahmed",
"Meron Admasu"
],
"abstract": "Objective: The main purpose of this study was to explore experiences of women who survived pre-eclampsia and eclampsia in Shashemene referral hospital and Melka Oda general hospital, 2021. Design: An institution-based exploratory qualitative study with a descriptive phenomenological study design Setting: The present study was conducted in Shashemene referral hospital and Melka Oda general hospital from March 03 to May 18, 2021. Participants: A total of 17 individual in-depth interviews (IDIs) were conducted with women who experienced and survived pre-eclampsia and eclampsia. Data were analyzed through thematic analysis using Atlas-ti software. Result: The present study revealed that women’s level of awareness on raised blood pressure and or convulsion occurring during pregnancy was poor. Barriers that limit pregnant women from getting treatment at the earliest point included misconception, lack of insight, failure to accept counseling from health care providers, low income, and influence from husbands. Discussions with the women in this study showed that these mothers were not counseled on danger signs during antenatal care check-ups. Almost all of the women were very concerned and frustrated due to their diagnosis. Conclusions: Women’s awareness of pre-eclampsia and eclampsia was poor and antenatal care was not offered as per expected quality. Improving awareness of hypertensive disorders in pregnancy and enhancing the quality of antenatal care is essential.",
"keywords": [
"Experiences",
"preeclampsia",
"eclampsia",
"survivors",
"Shashemene"
],
"content": "Strengths and limitations of the present study\n\n\n\n▪ As far as our knowledge is concerned, this the first study in Ethiopia investigating the lived experiences of women who have survived pre-eclampsia and eclampsia.\n\n▪ The study design employed a thorough investigation of lived experiences of women who survived pre-eclampsia and eclampsia in public hospitals of Shashemene Town.\n\n▪ The interviews were done in Afan Oromo and Amharic, the participants’ native language; therefore, the translation of the original language’s constructed meaning into English may have an impact.\n\n▪ Selection bias also exits due to the fact that women were recruited only from hospitals.\n\n\nIntroduction\n\nPre-eclampsia is a multi-system disorder, specific to pregnancy, that is commonly associated with raised blood pressure (≥140 mmHg/90 mmHg) and proteinuria which usually occurs after 20 weeks of gestation. Eclampsia is one or more convulsions in association with the syndrome of pre-eclampsia.1 Worldwide, pre-eclampsia complicates 2% to 8% of pregnancies whereas, in resource-poor countries, estimates of the incidence of eclampsia vary from 1/100 to 1/1700 deliveries.1\n\nPre-eclampsia and eclampsia are associated with increased complications including placenta abruption, preterm birth, fetal growth restriction acute renal failure cerebrovascular and cardiovascular complications, disseminated intravascular coagulation, and maternal death.2\n\nA systematic review from 40 countries that included nearly 39 million women estimated that 4.6% and 1.4% of all deliveries were complicated by pre-eclampsia and eclampsia, respectively, with a wide variation across regions.3 Maternal mortality from pre-eclampsia/eclampsia is highest in low- and middle-income countries (LMIC) and worldwide accounts for at least 63,000 maternal deaths per year.4\n\nEvidence shows that in Sub-Saharan African (SSA) countries, pre-eclampsia and eclampsia are among the top five leading causes of morbidity and mortality of women and neonates. Consequently, SSA countries experience the highest maternal and newborn mortality.5,6\n\nDespite efforts made to reduce maternal mortality in Ethiopia, there is still a high burden of maternal death. The estimate of the maternal mortality ratio according to the 2016 Ethiopian demographic health survey (EDHS) was 412 deaths per 100,000 live births.7 According to Ethiopian National Emergency Obstetric and Newborn Care (EMONC), 16% of direct maternal mortality and 10% of all maternal mortality (direct and indirect) was due to pre-eclampsia/eclampsia.8\n\nEarly diagnosis and management can help to reduce the dangers of pre-eclampsia and eclampsia and their complications; the majority of deaths related to this condition are avoidable when care is given at the right time. Avoiding delays and hindrances that are currently occurring in diagnosis and management are critical in this regard.9\n\nTo the best of our knowledge, so far, studies have not been conducted to explore experiences of women survived from pre-eclampsia and eclampsia in Ethiopia. Previous studies merely focused on prevalence and factors associated with pre-eclampsia.10,11\n\nTherefore, this study aimed to explore lived experiences of women who survived pre-eclampsia and eclampsia in Shashemene referral hospital and Melka Oda general hospital – the two public hospitals in the town. It identifies the barriers and enabling factors that affect their healthcare-seeking behaviors, and it describes ideas raised by these women to overcome these challenges.\n\n\nMethods\n\nAn institution-based exploratory qualitative study with a descriptive phenomenological study design was carried out from March 03 to May 18, 2021, at the two public hospitals of Shashemene town: Shashemene referral hospital and Melka Oda general hospital. Shashemene referral hospital is found in Shashemene town which is situated 238 km from Addis Ababa and nine Kms North of Shashemene town and Melka Oda general hospital, which is located in Shashemene town, 250 km away from the capital city, Addis Ababa.\n\nSample size determination\n\nThe sample size was estimated using previous methodological research12 conducted on similar topic, the level of information saturation, and the diversity of ideas among the participants. Saturation refers to sampling until no new data is received and redundancy is reached. Women were recruited until saturation and no new themes emerged. Interviews were conducted until additional interviews did not provide extra evidence about the main themes of interest. As a result, a total of seventeen individual in-depth interviews (IDIs) were conducted with women who experienced and survived pre-eclampsia and eclampsia.\n\nThe source populations were all women who suffered and survived from pre-eclampsia and eclampsia and were discharged from the hospitals. The study population encompassed all purposively selected women who suffered and survived from pre-eclampsia and eclampsia and were discharged from the hospitals.\n\nWomen who suffered and survived from pre-eclampsia and eclampsia and were discharged from the hospital were included in the present study whereas women who were not willing to participate in the study were excluded.\n\nA heterogeneous purposive sampling technique was employed to approach study participants. NG, AU, DY participated in the process. Individual in-depth interviews (IDIs) were conducted with women who suffered from pre-eclampsia and eclampsia, survived, and were discharged from the hospital. Information on socio-demographic characteristics, pregnancy, delivery, postnatal experiences, antenatal care (ANC), knowledge on pre-eclampsia and eclampsia, and factors that affect care-seeking at individual, household, community, and health systems levels were collected using a semi-structured interview guide. Instruments were pre-tested in Negelle Arsi Primary Hospital by authors to ensure that appropriate questions are being asked and that questions do not make respondents uncomfortable and/or confused because of combining two or more important issues in a single question. The pretest was approved by Institutional Review Board (IRB) of the University. Two people attended each interview; one conducted the interview and the other took field notes. Criterion followed while note taking include but not limited to taking basic information like study tile, PI of the study, season and date of data collection, geographic setting, demographics of the study participants, and setting. To maintain the integrity of the participants; from the very beginning, sufficient information was provided to study participants on the aim of the study, and they were also told that the information they offer.\n\nSemi-structured interview guides used in the present study were taken from a similar study conducted in Nigeria which were validated.12 Interview guide questions were prepared first in English, then translated to Afan Oromo, and Amharic and translated back to English to check for consistency by expert (health professional) who is familiar with both local languages and English. There were no changes made after the translation is made. 40–50 minutes were spent on the interview. Confidentiality was stressed in order to foster a relaxed atmosphere where participants may divulge more personal information and give an in-depth account of their experiences. Tell me more, what occurred next, and please elaborate were frequently used as prompts to extract additional information. During the data collection period, supplementary notes were taken through the non-participatory observation technique for non-verbal response and the context of the interview. The tape-recorded audio was checked for completeness and field notes were expanded soon after the end of each interview.\n\nTo assure the credibility of the study, the data collection process was completed at the data saturation point when no new information was obtained. The principal investigator and assistant have spent enough time with study participants in the field to explore sufficient data on the point of interest. Both the audio recorder and the field notes were used to collect data, and this enabled cross-checking. NG, AU and DY were collected data. Due to the fact that non-verbal replies are just as significant as verbal responses, this technique allowed us to ensure credibility of the study.\n\nMoreover, to assure dependability, the present study has clearly described the process selection of study participants, the process of data collection procedure, and the method of data analysis. To maintain transferability, the finding of the data was precisely described with sufficient details, and a thick description of data was provided by the principal investigator and Co-investigators. Lastly, to assure conformability, the audio and field note transcripts were compared and contrasted with the final research report so that to ensure consistency with original data, dependability, and conformability.\n\nData were analyzed by Atlas-ti software by applying thematic analysis. Researchers who want to reproduce our analysis and have no access for Atlas.ti (since Atlas.ti proprietary software) can use Qualcoder which is the best alternative. After listening repetitively to the audio record of individual IDIs, it was then transcribed verbatim into Afan Oromo and Amharic. The Afan Oromo and Amharic transcripts were then translated to the English language for analysis by the principal investigator and Co-investigators. The Afan Oromo, Amharic and English data were cross-checked for accuracy and completeness of the translation before analysis. All the transcripts were cautiously and repetitively read to become familiar with it. Codes were developed to extract meanings out of texts and were defined based on contained information, and central meaning. Then, codes were taken to build emerging themes. The translated primary documents, quotes, codes and interview guide questions are all available in our underlying and extended data.\n\n\nResult\n\nA total of 17women participated in this study. The age of participants ranges from 18-35 years (median age: 25 years). The number of children women had ranged from one to six. The median age of women at first birth was 19 years. Regarding educational status, three didn’t attend formal education, eight completed primary education, four secondary primary education, one has a diploma, and one has a BSc degree. A total of nine study participants resided in urban while eight resided in rural areas. Sixteen women had attended ANC check-ups during their current pregnancy. A total of four individuals had faced complications in their previous pregnancies. Of the women who had faced complication in their previous pregnancies, three women had pre-eclampsia and eclampsia previously while one woman had experienced antepartum hemorrhage. A total of five women had eclampsia while 12 had pre-eclampsia in the current pregnancy (Table 1).\n\nThe emerged themes in the current study include antenatal care services received and its quality, awareness of raised blood pressure and or convulsion during pregnancy, symptoms experienced, and quality of care received, women’s reaction towards the diagnosis, barriers, and suggested pieces of advice to improve health care services received by women who developed pre-eclampsia and eclampsia.\n\nAntenatal care is a maternal healthcare service provided by skilled health professionals to pregnant women. It is provided throughout pregnancy to ensure the best health outcomes for both the mother and neonates. The narratives of the women interviewed showed that different services had been offered to different patients at the antenatal care unit. Blood pressure measurement, urine test, blood test, tetanus toxoid vaccination, and ultrasound were done at the antenatal care unit.\n\nOne of the study participants explained the service she received as follows:\n\n“…they have measured my BP and weight. I have taken tetanus toxoid vaccination” (Participant 16, 20-year-old woman).\n\nAnother participant expressed that tablets for anemia and tetanus toxoid vaccination were given at the ANC unit.\n\n“They gave me tablets to prevent the occurrence of anemia. They also gave me vaccination here on my arm” (Participant One, 18-year-old woman).\n\nAnother participant said that only a blood test was done. She expressed that the health professionals simply examined her belly.\n\n“They did nothing. They simply examined me with their hands and sent me here (hospital). However, they have tested my blood” (Participant Two, 22-year-old woman).\n\nOne of the women stated that nothing had been offered to her while she attended ANC check-ups.\n\n“They didn’t do a urine test and also not measured my blood pressure” (Participant 5, 35-year-old woman).\n\nCounseling about danger signs is so vital issue that will enable pregnant women to come to a health facility at the earliest point when they develop the symptoms. Hence, complications can be reduced significantly.12 In this regard, most of the women said that they were not counseled for danger signs while they attend ANC check-ups during their current pregnancy.\n\n“They didn’t tell me these signs [danger signs]. I went for check-ups because I have some headaches. What enabled me to go to the health facility early was the experience I had during the last pregnancy. Unfortunately, they told me that it was common cold & come back home. I went to the health facility because I have fear that some complications might happen. This fear was due to complications that occurred during the last pregnancy. Nobody told me these danger signs” (Participant One, 18-year-old woman).\n\nAnother participant also shares the above experience in which she said that she wasn’t told the danger signs in detail.\n\n“They did not inform me that [danger sign]. They didn’t tell me in in detail. They simply told me to come back” (Participant 3, 18-year-old woman).\n\nOne of the study participants who developed eclampsia said that the health professional had not counseled her on danger signs.\n\n“They informed me nothing. I even asked the doctor if I come back for the check-up. The doctor told me that there is no need to come back. He (doctor) told me even I can give birth with no complication” (Participant Four, 30-year-old woman).\n\nThe other participant expressed that one should go repeatedly to receive counseling on danger sign\n\n“The health professionals have informed me nothing. But, to have such information one should go repeatedly. I went only once and therefore I didn’t get the chance of receiving such counseling” (Participant Five, 35-year-old woman).\n\nSimilarly, the other woman stated that she got the information from her previous experience. However, she said that she is not counseled during her current pregnancy.\n\n“They didn’t inform me this at all. I had this information during my first pregnancy. Because I suspected hypertension, I was the one who insist to check my BP. When I told them, I have suspected hypertension in the current pregnancy because I had it before, they overlooked my concern and said you will not develop hypertension for you had it in the past” (Participant Seven, 25-year-old woman).\n\nAnother woman stated that she has received counseling on danger signs. She listed the danger signs she was counseled on.\n\n“Yes, they have informed me…… Bleeding through the vagina before childbirth and also the passage of white discharge before the birth of the baby. They told me to come to the health facility as soon as possible if I see these signs”\n\n(Participant Six, 17 year-old woman).\n\nOne participant also stated that she was counseled for danger signs, and she has also listed the signs.\n\n“Yes, they have informed me. For instance, if the baby is not moving well, its weight is increasing rapidly, swelling of the body, they told me to come to a health facility as early as possible” (Participant 13, 29 year-old woman).\n\nWomen are requested to give opinions on the quality of antenatal care they received by the data collectors. One woman stated that the health professional didn’t evaluate her thoroughly and they “disrespected” her.\n\n“All professionals here (at the hospital) disrespected me. They didn’t evaluate me thoroughly. They didn’t serve patients properly” (Participant 13, 29 year-old woman).\n\nParticipant 16 also raised that the health professionals have no extensive experience and said they don’t treat mothers with respect. She also mentioned a lack of ultrasound equipment as a significant problem.\n\n“The shortcomings are: the facility is not neat, the doctors have no experience, and they didn’t treat mothers with respect, they don’t have an ultrasound. Ultrasound is available everywhere even at the level of kebeles [Kebele is the lowest administrative unit as per the context of study setting]. So, the lack of ultrasound is a significant problem. Health professionals working at the delivery unit are better in terms of the experience they have and the respectful care they provide. Health professionals working at the ANC unit disrespect women. They have no extensive experience. I am not happy with their work” (Participant 16, 20-year-old woman).\n\nOne of the study participants stated that the health professional working at the antenatal care clinic didn’t inform her as her blood pressure increased.\n\n“There (at ANC), they have checked my blood pressure. But they didn’t inform me that my BP is increasing and the stage of the disease. Otherwise, they have checked me thoroughly” (Participant 13, 29-year-old woman).\n\nOne other participant shares a similar idea to the above, in which she stated that the health professional didn’t inform her as her blood pressure was rising.\n\n“They did give me drugs. They did not inform me that my blood pressure is rising. When I come back in the third month, they told me that I had raised blood pressure. I was shocked at that moment. Finally, they transferred me to labour ward” (Participant 11, 25-year-old woman).\n\nOne of the women said that the lack of ultrasound was the shortcoming she noticed.\n\n“The shortcoming is lack of ultrasound. They didn’t check me by ultrasound [at the health center]. Here [at hospital], they checked by ultrasound and said the baby have malformation on its head. Here [at hospital], they said why you just stayed all these seven months. If they had an ultrasound, I wouldn’t have stayed all these months. So, the shortcoming is lack of ultrasound” (Participant Seven, 25-year-old woman).\n\nHowever, one of the women stated that she received the right ANC check-up.\n\n“They had given me the right service. They told me that the gestational age is seven months and two weeks in line with the information here (hospital)” (Participant Five, 35-year-old woman).\n\nStudy participants developed a wide range of symptoms including headaches, heartburn, loss of consciousness, epigastric pain, blurring of vision, fever, swelling face, and feet.\n\nOne of the study participants said she had a headache and blurring of vision.\n\n“I had a headache. I had also “qaanqee” before the headache [qaanqee is local Afan Oromo language term which means a blurring of vision]. I feel as if something has blown into my eyes. I had this symptom occasionally” (Participant One, 27-year-old woman).\n\nThis participant also stated that she had lost consciousness. She remembered the moment as follows:\n\n“During that time, I was sleeping. During the early morning I lost my consciousness. My families brought me here tell me that I have oral secretions. I came here by ambulance and finally gave birth” (Participant One, 27-year-old woman).\n\nAnother participant stated that she was experiencing epigastric pain and blurring of vision. This woman also lost her consciousness.\n\n“I had epigastric pain. After a moment, I developed a blurring of vision. Even before I had blurring of vision, I felt like seeing an object in a mirror. After I experienced these symptoms, I came here……. I lost my consciousness right after I arrived here” (Participant Four, 30 year-old woman).\n\nOne of the women stated that she has developed fever, swelling face, and feet.\n\n“I had a headache from the moment I develop fever and swelling of face and feet. The health professional told me that the swelling of feet has no significant impact and be vigilant on the swelling of face” (Participant Five, 35-year-old woman).\n\nThe other woman said that she developed fever, her feet swollen, and had heartburn.\n\n“I went there (health center) because I have an appointment. However, I had a fever. When I splash water on my body, it will be resolved. But, a few minutes later, it will start. My feet were swollen, and I had also heartburn. Then, I requested them to check my BP. When they check it, it was very high. Finally, they referred me to this hospital” (Participant Seven, 25-year-old woman).\n\nHowever, one of the study participants said that she had no symptoms at all.\n\nI don’t have these symptoms [blurring of vision, raised BP, headache] at all. They told me to watch these symptoms. I am waiting for these symptoms. But no such symptoms till now. If they told me I have raised blood pressure, my option is to accept their opinion (Participant 13, 29-year-old woman).\n\nStudy participants expressed the treatment they received after they arrived at the hospital. One of the women stated that health professionals were following her closely and administered drugs.\n\n“They are following me closely and giving me drugs” (Participant 12, 27 year-old woman).\n\nOther participants also stated satisfaction with the care given.\n\n“I am satisfied with the care given” (Participant Eight, 30-year-old woman).\n\nAnother study participant expressed that she received satisfactory care.\n\n“Well, I have received satisfactory care here. They saved my life here with the help of God. The health professionals here saved my life with the help of God, and I am so excited” (Participant Four, 30-year-old woman).\n\nThe other participant stated that her symptoms resolved after she received treatment at a hospital.\n\nRight after they gave me injections, I am fine. I have taken also pills and my headaches are gone (Participant Six, 24-year-old woman).\n\nDifferent reactions were observed when women were told they have hypertension. Several women were shocked, frustrated, anxious, and depressed when they heard their diagnosis.\n\nOne of the women stated that she was shocked when she was told she had raised blood pressure.\n\n“I was very shocked. I was having headache & blurring of vision at that moment. I was much stressed. Yesterday, they brought me here because I was very sick. But God gave me this child” (Participant 10, 20-year-old woman).\n\nThe other woman was also concerned when they told her she has hypertension.\n\n“I said to myself, are they again to terminate [a medical process of ending pregnancy after the fetus has reached the age of viability; not abortion] this pregnancy as before? I was shocked and disturbed. When they saw me as I am very worried, they counseled me not to be worried and told me that the baby will be born soon. They told me that the pregnancy has to be terminated. By counseling me thoroughly, they calm me” (Participant 11, 25-year-old woman).\n\nThe other study participant also said that she was concerned when they tell her she has hypertension. Besides, she said hypertension is so dangerous.\n\n“I know that raised blood pressure is dangerous. I was concerned. Then, I calmed down when they gave me drugs and told me that my BP is dropping” (Participant 13, 29-year-old woman).\n\nOne of the women expressed that it is so difficult to have raised blood pressure and it will also result in depression.\n\nIt’s so difficult to have raised blood pressure. The headache and swelling are so difficult. It will result in depression (Participant 17, 22-year-old woman).\n\nWomen’s level of awareness on raised blood pressure and or convulsion occurring during pregnancy was modest and poor. Most of the women (82.35%) were not aware that pregnant women may suffer from raised blood pressure and convulsions.\n\nOne of the women said she hadn’t heard of raised blood pressure in pregnant women.\n\n“I didn’t hear this raised blood pressure on pregnant women. This raised blood pressure occurs in mothers who stopped giving birth. I heard when neighbors say this woman has hypertension. But I didn’t see a pregnant woman who suffered & died from raised blood pressure. This raised blood pressure usually occurs in mothers who stopped giving birth. We need to restrain from consuming meals with high salt, black coffee, and stress. I didn’t see a pregnant woman who suffered from raised blood pressure” (Participant Eight, 30-year-old woman).\n\nMany of the other study participants didn’t know about raised blood pressure and convulsion occurring during pregnancy.\n\n“…I don’t know” (Participant 11, 25-year-old woman).\n\nHowever, one of the study participants mentioned the symptoms of raised blood pressure.\n\n“They said women who have raised blood pressure can’t stand, have headache on one side and blurring of vision. But I have not experienced this problem previously” (Participant 15, 26 year-old woman).\n\nMost of the women stated that raised blood pressure can cause maternal and fetal death. One of the women said that if raised blood pressure is left untreated it will cause hypertension and cardiac disease in the long run.\n\n“She [the mother] may develop hypertension and cardiac disease later on. The baby weight might be low and can be exposed for different diseases. Even they [both the mother & baby] might die” (Participant 16, 20-year-old woman).\n\nOne of the study participants expressed that the effect of raised blood pressure and convulsion may escalate to the level of death\n\n“…to the extent of death” (Participant 15, 26-year-old woman).\n\nOne of the women said that staying at home may cause death.\n\n“They need to check their blood pressure at a health center or a private clinic. If they simply stayed home, they may die. In the rural, they say it’s “Daataa” [A Local Afan Oromo Language which means blood which shaded during childbirth] and encourage women to stay home” (Participant 3, 18-year-old woman).\n\nOther women didn’t know the fate of a woman who was left untreated for raised blood pressure and/or convulsion.\n\n“I don’t know what happens to these women” (Participant 8, 30-year-old woman).\n\nStudy participants listed a wide range of barriers that limit pregnant women who developed raised blood pressure and or convulsion from getting treatment at the earliest point. These include misconception, lack of knowledge, fear of keeping children at home alone, low income, unsupportive husband, criticizing & blaming, and failure to be counseled by healthcare providers.\n\nWomen’s narratives suggested the presence of misconception in society on hypertensive disorders occurring during pregnancy. For instance, swelling of the face & feet during pregnancy is thought to be normal. They believe that blood is accumulated in the face & feet till childbirth, and hence they are swollen. According to the local language, this process is termed “Daataa”. The other misconception which was mentioned by the women was dryness of the head a responsible phenomenon for headache. Women also mentioned that these kinds of misconceptions are very risky as they may cost their lives.\n\nOne of the women stated this as follows:\n\n“They [some of the women] believe that swellings of face & feet are a normal event. These swellings occur during the stage of childbirth. Until childbirth, the blood stays in the feet and face, and they name it “Daataa” [a local Afan Oromo Language term which means blood shaded during childbirth]). People in rural areas believe that severe headache is due to dryness of the head. Because of these, misconception among mothers will cost their lives. It is very important to check blood pressure. Not only mothers, but it will also be better if all individuals check their blood pressure. If you take my situation, firstly, I came here for leakage of fluid. However, as days passed, I developed raised blood pressure. So, if I were at home, I would have missed the opportunity of knowing of the problem” (Participant Eight, 30-year-old woman).\n\nThe other woman also shares the idea of the above mother.\n\n“There is a misconception in the society. For instance, when I suffered from hypertension during the last pregnancy, my face and legs were swollen. Society perceives that the swollen face and legs are due to blood during pregnancy. They told me it was “daataa” and that’s why you are gaining weight” (Participant One, 27-year-old woman).\n\nWomen reported a lack of knowledge to be the barrier to receiving adequate care. Sufficient knowledge of pre-eclampsia & eclampsia contributes significantly to its prevention, management, and treatment. Knowledge of the patient’s illness has significant benefits in terms of treatment compliance and helps reduce illness-related complications. One of the women said that lack of knowledge is a barrier to not getting early treatment.\n\n“It’s lack of knowledge. If she has sufficient knowledge on hypertension, she will go to a facility to get the necessary treatment. Nobody wants to suffer from disease” (Participant Five, 35-year-old woman).\n\nThe other woman also supported the above idea.\n\n“It’s lack of insight. If you lack insight, you will face complications” (Participant Nine, 20-year-old woman).\n\nOne of the women said that lack of insight and failure to accept counseling of health professionals are factors that limit women.\n\n“I think it is because they have no insight and failure to accept counseling from health professionals” (Participant 11, 25-year-old woman).\n\nThe other study participant shared a similar idea and additionally stated that there is criticizing and blaming.\n\n“Lack of insight on this issue. Some mothers might say rather than going to a health facility it is better to gather information from women in the community. This is because they lack knowledge. There is also criticizing and blaming each other” (Participant 16, 20-year-old woman).\n\nWomen mentioned a lack of husband support to be responsible for not getting treatment. Men’s role as a major decision-maker and a major supplier of economic resources in developing countries can strongly influence wives’ choices in health-seeking behavior. Husbands may limit the mothers from getting treatment. Women described a financial barrier as a factor for not getting treatment. This is also related to the lack of support from her husband.\n\nOne of the mothers stated that fear of keeping children alone at home, lack of husband support and low-income limits women from getting treatments\n\n“If they have children, they believe that if they come to health facility their children at home will not be safe. Husbands might limit the woman from going to health facilities by telling her she is normal. There is a husband that limits his wife from using family planning. They didn’t come even for ANC check-ups unless they get permission from their husband. Their income will also limit them. She might not have money even for transport and other expenses. I think these are the reasons” (Participant 13, 29-year-old woman).\n\nStudy participants forwarded plenty of ideas on the way that pregnant mothers suffering from raised blood pressure and convulsion can access and receive sufficient treatment at the earliest point. These include ANC check-ups regularly, counseling & encouraging mothers, coming to a hospital at the earliest point, husband support, receiving advice only from health professionals, support from families and health professionals, and arranging referrals for the complicated cases.\n\nOne of the study participants said that mothers should go regularly for ANC check-ups, and the need to counsel, inform, and encourage mothers.\n\n“The mother should go regularly for ANC check-up. We [other community members] need to inform, counsel, and encourage mothers to come to a health facility. The government and families should encourage the mothers to visit health facilities when they develop symptoms related to hypertension or other health problems” (Participant One, 27-year-old woman).\n\nThe other study participants also said mothers should come to a hospital at the earliest point and families and health professionals should help them.\n\n“If she didn’t lose her consciousness, she needs to say bring me to hospital. She needs to come to the hospital earlier. It’s really difficult if her family didn’t encourage and support her [women]. That will be good if she lacks interest than if they lack interest in going to a health facility. They need to treat mothers. They need to give drugs on time” (Participant 10, 20-year-old woman).\n\nAnother mother also shared a similar idea with the above study participants.\n\n“Firstly, mothers need to get ANC check-ups. They need to have regular ANC check-ups. They will know their status when they have ANC check-ups. Besides, their families need to support them. Families need to counsel them to avoid worry. Families need to encourage her and fulfill all required things. Health facilities need to provide all necessary treatments. They need to provide required treatment” (Participant 13, 29-year-old woman).\n\nSimilarly, the other mother said that health facilities should refer cases beyond their capacity.\n\n“Health facilities need to treat the mothers. However, if it is beyond their capacity, they need to transfer the mother to the best set-up” (Participant 15, 26-year-old woman).\n\nOne of the study participants also raised husbands should support their wives and mothers should receive information from health care providers.\n\n“Every husband, whether educated or uneducated, needs to support his wife. Mothers should receive information from health professionals. The doctors need to respect and give due attention for the baby for we don’t know the destiny of that baby” (Participant 16, 20-year-old woman).\n\n\nDiscussion\n\nThe current study explored the experiences of women who suffered and survived pre-eclampsia and eclampsia in the public hospitals of Shashemene Town, within the Oromia Region, of Ethiopia. The emerged themes in the current study include antenatal care services received and their quality, awareness on raised blood pressure and or convulsion during pregnancy, symptoms experienced, and quality of care received, women’s reaction towards the diagnosis, barriers, and suggested advice to improve health care services received by women who developed pre-eclampsia and eclampsia.\n\nThe present study showed that women’s level of awareness on raised blood pressure and or convulsion occurring during pregnancy was modest and poor. Most of the women were not aware that pregnant women may suffer from raised blood pressure and convulsion. The current finding is in line with the study conducted in Brazil by Lima de Souza N et al. which revealed unawareness of women about eclampsia during prenatal care. They only became aware after hospitalization or by the imminent premature delivery.11\n\nThis finding is in line with a study carried out in Nigeria where only a few study participants associate eclampsia with raised blood pressure.13,14 Similarly, the finding is consistent with the study conducted in Ghana which reported a high prevalence of inadequate knowledge of pre-eclampsia among the pregnant study population.15\n\nWomen’s discourse in the present study revealed that raised blood pressure can cause maternal and fetal death. This finding is consistent with the study done in Southwestern Uganda which showed that participants were aware of the potential consequences of the symptoms of eclampsia and mentioned that the condition could lead to the death of the baby in utero or even the mother.16 Similarly, the present study is in line with the study done in India in which study participants mentioned the most serious and most commonly cited consequences of hypertension or seizures in pregnancy to be the death of the mother and/or infant.17\n\nParticipating women’s narratives in the present study revealed that mothers might not have money even for transport and other expenses. This was one of the factors that limit pregnant women who developed pre-eclampsia and eclampsia from accessing and getting treatment from health facilities. This finding is supported by the recent study carried out among survivors of pre-eclampsia and eclampsia in which financial barriers affected access to transportation and affordability of health services or medicines.17\n\nWomen also mentioned misconception as a barrier for not getting treatment at the earliest point. They stated that swelling of the face & feet during pregnancy is thought to be normal within socio-cultural context. They believe that blood is accumulated in the face & feet till childbirth, and hence they are swollen. Similarly, in a study conducted in Nigeria, it was found that spirituality and tradition affected women’s lives profoundly, which has significantly affected care-seeking decisions.12 Such misconception in society may delay mothers or make them stay at home which may result in life-threatening complications.\n\nWomen’s discourses in our study also revealed that unsupportive husbands are barriers to not getting treatment. Husbands are mostly the only financial contributor to a family, and thus the single decision-maker in a family. Therefore, if they are uncooperative, they can significantly delay healthcare seeking or forbid the mothers from going to health facilities. This finding is supported by a study carried out in Nigeria12 & Bangladesh.18\n\nIn the present study, women were often not counseled on danger signs, and, as a result, they didn’t know these signs when they experienced them. Few women mentioned that women who have raised blood pressure can’t stand, have headaches on one side, and blurring of vision. But, in the study carried out in India women reported signs or symptoms of pre-eclampsia were sweating, fatigue, dizziness-unsteadiness, swelling, anger, talking too much, frothing, shaking, eyes rolling upwards, clenching teeth, and tongue biting.17\n\nWomen’s narratives showed that they were very concerned when they were told that they had hypertension, which they described to be so dangerous. Study subjects also expressed that it is difficult to have raised blood pressure and it will also result in depression.\n\nThe present finding is consistent with the study done in Australia where understandably, women were very concerned about the life-threatening nature of pre-eclampsia and focused their attention on the consequences of pre-eclampsia across different end-organs, including brain, liver, and kidneys.19\n\nThe present study is also in line with the study in which women described that they were afraid of this disease because they thought that not only themselves but also their babies were at risk and even death and also, they had negative emotions and thoughts when suffering pre-eclampsia. Sadness, frustration, or low-spiritedness were their usual emotions.20\n\nParticipating women’s narratives suggested that every husband, whether educated or uneducated, needs to support her to enhance access to health care services. Besides, they described the importance of support from families & society as a key tactic for mitigating complications from pre-eclampsia & eclampsia. This finding is in line with the study done in Nigeria which showed that engaging in discussions with family and communities emerged as a critical cue to action as these groups often provide instrumental support in women’s ANC and delivery care-seeking.12\n\nWomen’s discourses suggested the importance of regular ANC check-ups to avert complications of pre-eclampsia and eclampsia. ANC allows early detection & management of complications. They also mentioned the importance of counseling on danger signs of pregnancy during ANC check-ups. This finding is supported by a study conducted in Indonesia which revealed that antenatal care visits affect early detection of pre-eclampsia, and pregnant women who regularly make antenatal visits can prevent possible dangers of pregnancy as early as possible.21\n\n\nConclusion\n\nThe present study showed that most of the women were not aware that pregnant women may suffer from raised blood pressure and convulsion. Women were not sufficiently counseled on danger signs during their antenatal care. Women experienced frustration and fear when they heard their diagnosis. Furthermore, participants perceived that quality antenatal care was not offered for the women. Misconceptions, unsupportive husbands, insufficient knowledge, and low income were identified as barriers to not getting treatment at the earliest point. Suggested advice for averting complications from pre-eclampsia and eclampsia include ANC check-ups regularly, counseling & encouraging mothers to come to a hospital at the earliest point, husband support, receiving advice only from health professionals, support from families and health professionals, and arranging referrals for the complicated cases. Improving awareness on hypertensive disorders in pregnancy among mothers and the community through health extension workers and community leaders, enhancing the quality of ANC check-ups provided, and strengthening counseling service provided on danger signs of pregnancy while women attend antenatal care is pivotal. Besides, every effort has to be made to change the belief & misconceptions held by society about pre-eclampsia and eclampsia. Encouraging husbands to involve in the care of their wives is also invaluable. The community, families & health care providers are expected to provide all the required support & care for women with pre-eclampsia & eclampsia.\n\n\nEthical considerations\n\nEthical approval was taken from Madda Walabu University, Shashemene campus, research, and community service coordinating office (reference number: R/C/S/T/T/014/13). Formal letters were obtained from officials of respective hospitals. In addition, informed verbal consent was obtained from study participants because the study participants were uneducated, and this was approved by Institutional Review Board (IRB) of the University. The consent form were translated in to local language and data collector read out for the respondents and took consent before commencing data collection. The consent was narrated to the participants and their responses were tape-recorded. Respondents were notified about their right to refuse or terminate at any point of the interview. The information that was provided by each respondent was kept confidential. All personal identifiers were removed from transcripts and quoted texts. In addition, the Institutional Review Board (IRB) of the University approved the pre-testing of the instruments at Negelle Arsi Primary Hospital and protected the rights of the study participants.",
"appendix": "Data availability\n\nZenodo: Lived experiences of women who survived from pre-eclampsia and eclampsia in Public Hospitals of Shashemene Town, Oromia Region, Ethiopia: a qualitative study, https://doi.org/10.5281/zenodo.7576222. 22\n\nThis project contains the following underlying data:\n\n- Negeso project.atlcb (which contains primary translated document, quotes and codes)\n\nThis project contains the following extended data:\n\n- S1 Interview Guide Question.docx.\n\nData are available under license Creative Commons Attribution 4.0 International (CC BY 4.0).\n\n\nAcknowledgments\n\nWe want to express our profound gratitude to respondents, officials from respective health facilities without whom this research work would not have been possible.\n\n\nReferences\n\nGestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet. Gynecol. 2020; 135(6): e237–e260. Publisher Full Text\n\nPortelli M, Baron B: Clinical Presentation of Pre-eclampsia and the Diagnostic Value of Proteins and their Methylation Products as Biomarkers in Pregnant Women with Pre-eclampsia and Their newborns. Hindawi: J. Pregnancy. 2018; 2018: 1–23. Publisher Full Text\n\nAbalos E, Cuesta C, Grosso AL, et al.: Global and regional estimates of pre-eclampsia and eclampsia: A systematic review. Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 170: 1–7. PubMed Abstract | Publisher Full Text\n\nGoldenberg RL, Mcclure EM: Maternal, fetal and neonatal mortality: lessons learned from historical changes in high-income countries and their potential application to low-income countries. Maternal Health Neonatol. Perinatol. 2015; 1(3): 3. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlkema L, Chou D, Hogan D, et al.: Global, regional and national levels and trends in maternal mortality between 1990 and 2015, With Scenario-based projections to 2030: a systematic analysis by UN Maternal Mortality Estimation Inter-Agency Group. Lancet. 2016; 387: 462–474. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCSA: Central Statistical Agency. Ethiopian Demographic and Health Survey. Ethiopia: Addis Ababa; 2016. Reference Source\n\nGym A, Bailey P, Pearson L, et al.: Disease burden due to pre-eclampsia/eclampsia and the Ethiopian health system’s response. Int. J. Gynaecol. Obstet. 2011; 115: 112–116. PubMed Abstract | Publisher Full Text\n\nMaternity World Wide: The Three Delays Model and Our Integrated Approach.2014. Reference Source\n\nBelay AS, Wudad T: Prevalence and associated factors of pre-eclampsia among pregnant women attending anti-natal care at Mettu Karl referral hospital, Ethiopia: cross-sectional study. BMC Clinical. Hypertension. 2019; 25(14). Publisher Full Text\n\nTessema GA, Tekeste A, Ayele TA: Pre-eclampsia and associated factors among pregnant women attending antenatal care in Dessie referral hospital, Northeast Ethiopia: a hospital-based study. BMC Pregnancy Childbirth. 2015; 15(73): 73. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLima de Souza N, Fernandes Araújo AC, Dantas de Azevedo G, et al.: Percepção materna com o nascimento prematuro e vivência da gravidez com pré-eclampsia [Maternal perception of premature birth and the experience of pre-eclampsia pregnancy]. Rev. Saude Publica. 2007 Oct; 41(5): 704–710. Publisher Full Text\n\nSripad P, Kirk K, Adoyi G, et al.: Exploring survivor perceptions of pre-eclampsia and eclampsia in Nigeria through the health belief model. BMC Pregnancy Childbirth. 2019; 19: 1–11. Publisher Full Text\n\nAssaf S: Counseling and Knowledge of Danger Signs of Pregnancy Complications in Haiti, Malawi, and Senegal. Matern. Child Health J. 2018 Nov; 22(11): 1659–1667. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAdamu AN, Tunau K, Hassan M, et al.: The perception of patients’ relations on the cause of Eclampsia. Gynecol. Obstet. 2014; 04: 1–4. Publisher Full Text\n\nFondjo LA, Boamah VE, Fierti A, et al.: Knowledge of pre-eclampsia and its associated factors among pregnant women: a possible link to reduce related adverse outcomes. BMC Pregnancy Childbirth. 2019; 19: 1–8. Publisher Full Text\n\nNabulo H, Ruzaaza G, Mugabi F, et al.: Perceptions on pre-eclampsia and eclampsia among older women in rural southwestern Uganda. BMC. Reprod. Health. 2020; 20.\n\nVidler M, Charantimath U, Katageri G, et al.: Community perceptions of pre-eclampsia in rural Karnataka State, India: a qualitative study. Reprod. Health. 2016; 13(Suppl 1): 35. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDempsey A, Sripad P, Sultana K, et al.: Pathways to service access for pre-eclampsia and eclampsia in rural Bangladesh: Exploring women’s care-seeking. PLoS One. 2021; 16(2): e0245371. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDuffy J, Thompson T, Hinton L, et al.: What outcomes should researchers select, collect and report in pre-eclampsia research? A qualitative study exploring the views of women with lived experience of pre-eclampsia. BJOG. 2019; 126: 637–646. PubMed Abstract | Publisher Full Text\n\nVærland IE, Vevatne K, Brinchmann BS: Mothers’ experiences of having a premature infant due to pre-eclampsia. Scand. J. Caring Sci. 2017; 23: 1–8.\n\nFadilah DR, Devy SR: Antenatal Care Visits and Early Detection of Pre-eclampsia among Pregnant Women. Int. J. Public Health Sci. 2018; 7(4): 248–253.\n\nGebeyehu N, Urgessa A, Yohannes D, et al.: Zenodo: Lived experiences of women who survived from pre-eclampsia and eclampsia in Public Hospitals of Shashemene Town, Oromia Region, Ethiopia: a qualitative study.Publisher Full Text"
}
|
[
{
"id": "250739",
"date": "21 Mar 2024",
"name": "Marianne Johansen",
"expertise": [
"Reviewer Expertise Preeclampsia"
],
"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 exploratory qualitative study by N Gebeyehu et al on the lived experiences of 17 women who have all experienced preeclampsia or eclampsia in two public Ethiopian hospitals - one general and one referral hospital - is generally an important and well conducted study.\nThe authors and investigators address and explore some very important issues on different aspects like levels of awareness of the preeclampsia syndrome in the general population and at a healthcare level in the ANC, misconceptions in the society, barriers to access to healthcare and the the level of quality of counselling and healthcare provided. Importantly, the interviewed women bring suggestions to the table on how healthcare counselling and better access to qualified healthcare may improve the clinical outcome in the region for women suffering from preeclampsia. These are all very essential issues to address in order to better inform healthcare workers on how to improve counselling of women in Ethiopia on preeclampsia and eclampsia; both still potentially severe and life threatening conditions for both mother and child. I would like to commend the authors for addressing this very important topic as preeclampsia and eclampsia is still one of the leading causes of maternal mortality in the Sub-Saharan African countries.\nHowever, I have some general and some more specific comments in relation to the submitted paper.\nGeneral comments: Generally a well written manuscript. However, I find that the manuscript is too long and with many repetitive quotes in the result section. One suggestion would be to put the quotes in themed boxes for each of the respective emerged themes; Antenatal care service offered and its quality, Symptoms experienced and quality of care received, Barriers to receiving treatments from health facilities, Misconceptions, lack of knowledge, Unsupportive husband and low income, and Suggested advice for mothers, families and health facilities. I also suggest that the overall number of quotes appearing in the manuscript is reduced, as several of the quotes are very alike from a thematic perspective.\n\nBesides, the manuscript would benefit from a thorough proof reading by a native English speaking person.\n\nSpecific comments: Women are quoted for saying that access to health care services is lacking. In this context it would be relevant to mention whether prescribed medicine is free of charge?\nI am curious to know whether women who participated did in any way differ from women who rejected to participate. Also, I would like to know how many women were invited to participate to allow for 17 participants?\n\n5/17 of the participants suffered eclampsia. Is this a normal proportion amongst women with preeclampsia in Ethiopia? Please specify.\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?\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": []
},
{
"id": "304794",
"date": "16 Aug 2024",
"name": "Margaret P. Kasaro",
"expertise": [
"Reviewer Expertise Women's healthHmaternal and child 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\nHypertensive disorders in pregnancy are an important contributor to maternal morbidity and mortality. This is a write up on the experiences of the women who survived preeclampsia and eclampsia for knowledge of symptomatology, antenatal services - information and education on danger signs, referral and management of the disorder. The study has highlighted gaps in the health care delivery as experienced by the women who survived the disorder but in conclusion has not included the implications and recommendations in working towards effective engagement. Here are few comments to consider for the next version of the paper:\nStrengths and limitations 1.The study design may need to be reconsidered to be mentioned as a strength of there study 2. If the translation process was rigorous to ensure the meaning is not lost in translation, can this point still be a limitation 3. Selection bias exists not exits\n\nIntroduction 1. Does the use of the words commonly and usually in the definition of Preeclampsia affect the meaning here? 2. Paragraph 2, 3 and 4 are repetitious in the discussion of effects of PE and eclampsia please edit 3. Paragraph 5 there is repeating of a sentence. In editing consider including how data on experiences may be used to reduce the negative effects of the disease\nSample size calculation 1. It may not be necessary to explain when to stop sampling plus there is repeating\nData collection 1. Please note the repetition of sampling techniques description 2. Naming the staff who were actually doing the data collection should be reserved for an appropriate section 3. Last sentence in paragraph 1 is not clear 4. In paragraph 2 please consider the following:\nYou have described the translation process, is it rigorous not to have information lost in the process? The relationship between confidentiality and discomfort Indicate that open ended questions and probing were used rather that specific questions Is collection to saturation equal to credibility Data collected is collectors In the last sentences - which technique is being referred to for the nonverbal Dependability, transferability and conformability confirm the meaning in this context\n\nAnalysis Overall consider editing the analysis section to use standard format of reporting qualitative analysis then consider removing the bold in the sentence … translation by PI and co investigators\n\nResults\nPlease pay attention to the tenses space between 17 and women In sentence number 2 edit to add bold word as follows - the number of children that the women\n\nThemes\nQuality of care is repeated Please clarify on the suggested pieces of advice\n\nANC\nEdit the sentence to clarify if each participant reported different care or is it their interpretation that care offered to women varies Last sentence suggested edit - Services that women reported to have received included...… Women requested to give opinions on the quality …. by data collectors may imply the care was provided by the data collectors\n\nWomen's reactions Consider not explaining what procedure to terminate means\nBarriers\nRepeating meaning of daataa Consider rephrasing the unsupportive husbands and low income/advice preamble\n\nDiscussion\nParagraph one summarises the findings well Tackle each theme in order of how presented in paragraph 1 Women's discourse could be edited with synonyms\n\nConclusions Please consider editing the conclusion without repeating results in detail and put in implications and recommendations\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? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-1464
|
https://f1000research.com/articles/13-15/v1
|
04 Jan 24
|
{
"type": "Research Article",
"title": "Facilitation of practical work in Natural Sciences: experiences and approaches of junior teachers",
"authors": [
"Lettah Sikhosana",
"Khutso Charles Mogale",
"Khutso Charles Mogale"
],
"abstract": "Background This paper explored junior teachers’ experiences and approaches when facilitating practical work in Natural Sciences during teaching and learning. Grade 7 is the final year of primary school in South Africa, with students between the ages of 11 to 13. The researchers observed that there are enormous challenges encountered by junior grade 7 teachers when preparing, designing and conducting practical work in Natural Sciences teaching and learning.\n\nMethods A qualitative multiple case study design was used. Three grade 7 Natural Sciences junior level teachers were selected purposively as participants. Data was collected through classroom observations, semi-structured interviews and document analysis.\n\nResults The findings of this study revealed that some grade 7 junior Natural Sciences teachers were overwhelmed when facilitating practical work during teaching and learning. In addition, some of the grade 7 junior Natural Sciences teachers were unable to maintain discipline inside and outside the classroom environment when conducting practical work and demonstrations. The grade 7 junior Natural Sciences teachers had to use mechanism to cope with the demands associated with facilitation of practical work in Natural Sciences teaching and learning. Some of the approaches adopted by the grade 7 junior Natural Sciences teachers when facilitating practical work in Natural Sciences teaching and learning included group work, observations, demonstration, illustrations, projects and inquiry-based scientific investigations.\n\nConclusion It is recommended that teachers be professionally trained on how to facilitate practical work to advance the new ways of teaching and learning as advocated by per the Curriculum Assessment Policy Statement document while empowering them with pedagogical content knowledge to enable them to achieve the aim and objectives of practical work in Natural Sciences teaching and learning.",
"keywords": [
"Practical work",
"Novice teacher",
"Natural Sciences",
"Professional development",
"Approaches",
"Experiences",
"Pedagogical content knowledge"
],
"content": "Introduction\n\nStarting a new career path in the field of education comes with unrealistic expectations about teaching which may result in negative and stressful experiences for teachers that are junior (Dias-Lacy & Guirguis, 2017). Junior teachers can be best described as teachers that are in their first year of teaching with little teaching experience or no prior teaching experience (Makoa & Segalo, 2021). Despite the efforts made by the Department of Basic Education and the Department of Higher Education and Training in South Africa to support junior teachers, challenges experienced by these teachers persist (Esau & Maarman, 2021). Studies conducted in countries such as Turkey, Pakistan, United States of America and Qatar revealed that junior teachers lack adequate professional support and may feel unprepared to handle academic issues and manage learner behaviour (Ahmed et al., 2020; AL-Naimi et al., 2020; Ross-Hain, 2020; Kozikoğlu and Senemoğlu, 2018). It is imperative to acknowledge that pervasive challenges are not only confined to junior teachers within the African continent as they are also widely experienced by other teachers across the globe (Lodge et al., 2018; Abdurrahman, 2016).\n\nIn the past two decades, the Department of Basic Education (DBE) in South Africa experienced a massive loss and reduction of teacher population due to various reasons. These reasons included among others: resignation of teachers for greener pastures, unhealthy working conditions in teaching fraternity especially salaries, retirement of teachers, unmanageable workloads and unsafe school environment (South African Democratic Teachers Union [SADTU], 2022). Certain schools were left without scarce skills teachers who were responsible for teaching gateway subjects such as Mathematics and Science. Despite the efforts made by the Department of Basic Education and other stakeholders to increase the number of experienced teachers with scarce skills, South Africa is still far from achieving this desired outcome (Muremela et al., 2021). This resulted in an increase of teaching workload for the few remaining teachers in some schools and junior teachers entering the field of education.\n\nOn the other hand, in some South African schools, Natural Science subjects are often allocated to an unqualified teacher while the school waits for the posts to be advertised and filled by a qualified teacher, which in most cases would be junior teachers (Ntuli et al., 2022). In some South African schools, scarce skilled teachers were replaced with less experienced and unqualified teachers to teach Natural Sciences (Esau & Maarman, 2021). However, the SADTU general secretary, Mugwena Maluleke, refuted this claim by indicating that the problem was not that teachers were not qualified‚ it was that they were being made to teach the wrong subjects and misallocation of resources (Maluleke, 2021). In 2021, the Minister of Basic Education, Angie Motshekga, revealed that there are 1575 unqualified and under-qualified teachers teaching in South African schools; with 218 of them appointed as permanent employees (Motshekga, 2021). The Minister of Basic Education further added that “Over the years the Department has implemented various programmes, particularly, to assist un-and-under-qualified educators to improve their qualifications”.\n\nThe National Professional Diploma was implemented as an interim qualification for upgrading under-qualified teachers (Mhlaba & Rankhumise, 2022). However, inadequate attention is devoted to professional development, training, skills development and technical support to enhance communication skills and manage the curriculum as support mechanism for junior science teachers (Mhlaba & Rankhumise, 2022). Hence, this paper explores junior grade 7 teachers’ experiences and approaches when facilitating practical work in Natural Sciences teaching and learning. Grade 7 is the final year of primary school in South Africa, with students between the ages of 11 to 13. This is because practical work is a prominent and distinctive feature of science education which must be carried out by learners as an essential element of good science teaching (Sshana & Abulibdeh, 2020). It is for this reason that the Curriculum Assessment Policy Statement (CAPS) document clearly prescribed the following activities to be executed by Natural Sciences teachers every year: 25% for practical work and 75% for the theory work in which four practical tasks must be recorded per year, one per quarter for assessment purpose (Department of Basic Education [DBE], 2015).\n\n\nLiterature review\n\nThere are various kinds of practical work that are prescribed in the Curriculum Assessment Policy Statement (CAPS). These include observations, scientific investigation, scientific enquiry, illustration, demonstration, experiments, projects, models, problem solving, case study, fieldwork, drawings, paintings, constructions, interviews, laboratory work, assignments (DBE, 2015; Stoffels, 2005). These types of practical work enable the teacher to involve learners in teaching and learning process where they also get an opportunity to work in pairs or in groups while the teacher plays a role of being a complete observer or silent observer (Monteiro et al., 2021). Teachers are guided by the CAPS document which stipulates clearly the type of practical work that must be done per grade and per term in Natural Sciences subject in the senior phase (DBE, 2015). According to DBE (2011), demonstrations, observations, models, investigations, assignments, projects, and illustrations were the most commonly prescribed strategies for facilitating practical work in grade 7. However, from one of the researchers experience as a Natural Sciences teacher, it was evident that demonstrations were the most preferred type of practical work and which were also highly favoured by most Natural Sciences teachers. Furthermore, they preferred to perform practical work while learners are observing and listening, reason being that they are not good in facilitation, so they rather demonstrate than facilitating the activity.\n\nThe goals of Natural Sciences education through effective practical work bring into perspective the scarcity of skills that are associated predominantly with the Natural Sciences in which secondary school education plays a crucial role as a preparation and initiation phase into the fields (Department of Higher Education and Training [DHET], 2014). Shortages of critical skills in the fields of science and engineering are common in most developing countries, including South Africa. Education is one of key drivers of the economy as it enables accomplishment of national curriculum goals (Nyoka et al., 2014). Accordingly, inquiry-based practical work is aimed at improving learner engagement and learner-centeredness which involves investigations conducted by learners in contextualised and relevant experiences (Aubusson, 2011). Hence, learners are given opportunities to conduct investigations in ways that are scaffolded to meet the levels of their skills and knowledge (Allchin, 2014). This shows that practical work does provide learners with insights into scientific practice and increases their interests in science field and studies (Millar, 2011). It also develops learners’ understanding of the logic of scientific inquiry and the nature of scientific knowledge as a curriculum which can be used as a tool for teaching about experimental design.\n\nPractical work in the context of South African CAPS document gives practical expression to the knowledge, skills and values worth learning in South African schools (DBE, 2011). The Natural Sciences CAPS document is aimed at ensuring that learners acquire and apply knowledge and skills in ways that are meaningful to their own lives. Therefore, Natural Sciences teachers are expected to demonstrate adequate pedagogical content knowledge. Hence, the CAPS document promotes knowledge development in local contexts, while being sensitive to global imperatives (DBE, 2015). The CAPS document prescribed practical work as part of final promotional assessment which Natural Sciences teachers are compelled to implement in accordance with the three specific aims of Natural Sciences in grade 7 such as: (1) Doing science, (2) Knowing the subject content and making connections, and (3) Understanding the uses of Science (DBE, 2015).\n\nThe researchers observed that there are enormous challenges experienced by grade 7 junior teachers when in preparing, designing and conducting practical work in Natural Sciences teaching and learning. These challenges are the key hindrances towards the accomplishment of national curriculum goals (Nyoka et al., 2014). This paper was also influenced by the anecdotal statistics taken during the Natural Sciences briefing workshops that occurred in the beginning of each year, in which junior and experienced Natural Sciences teachers participated. These experiences prompted the researchers to explore how grade 7 junior teachers facilitated practical work in Natural Sciences subject during teaching and learning.\n\nOur main research question is ‘How do grade 7 junior teachers facilitate practical work in Natural Sciences teaching and learning?’. The following research sub-questions guided this paper: 1) What are the experiences of grade 7 junior teachers when facilitating practical work in Natural Sciences teaching and learning? 2) What pedagogical approaches are adopted by the grade 7 junior teachers when facilitating practical work in Natural Sciences teaching and learning?\n\nIn addition, the following objectives guided the study: To document grade 7 junior teachers’ experiences of facilitating practical work in Natural Sciences teaching and learning. To identify pedagogical approaches adopted by grade 7 junior teachers when facilitating practical work in Natural Sciences teaching and learning.\n\n\nMethods\n\nThe Unisa College of Education, South Africa, Ethics Review Committee approved this study (approval number 2017/06/14/31144187/5/MC) (Sikhosana & Mogale, 2023d). Written informed consent was obtained from participants prior to data collection. To ensure confidentiality and anonymity, the participants were assured that all the personal information they provided will be protected. As a result, pseudonyms were used when signing the confidentiality forms and throughout the study.\n\nA qualitative interpretative case study was used to explore grade 7 junior teachers experiences and approaches when facilitating practical work in Natural Sciences teaching and learning. An interpretative research paradigm enabled us to understand and interpret lived experiences, views and perceptions of grade 7 junior teachers in their social context (Kivunja & Kuyini, 2017). In our endeavour to understand how grade 7 junior Natural Sciences teachers conducted practical work, we focused on the following 2 themes:\n\n1. Experiences of grade 7 junior teachers when facilitating practical work in Natural Sciences teaching and learning.\n\n2. Pedagogical approaches adopted by grade 7 junior teachers when facilitating practical work in Natural Sciences teaching and learning.\n\nThree junior grade 7 teachers who taught Natural Sciences subject were sampled purposefully based on the purpose of this paper with the belief that each participant will provide rich and unique data (Suen et al., 2014). These teachers were classified as junior teachers as they had a teaching experience of less than 1 year. However, they were all qualified to teach Natural Sciences subject. Table 1 describes the demographic profile of each junior grade 7 teacher. For the purposes of this research analysis, a first year teacher will refer to an individual who entered the field of education and is teaching for the very first time in their career. As such the inexperience of a first-year teacher leads to high level of stress (Dias-Lacy & Guirguis, 2017).\n\nThe setting of this study was in three primary schools in Lebopo circuit, situated around a rural area in Molepo villages, in Polokwane, Limpopo province within the Republic of South Africa. The community’s socioeconomic status is precarious, as most residents are unemployed. These primary schools are classified as quintile 1 schools, which means they are a fee-free paying schools with limited infrastructure and resources. The Lebopo circuit is one of the five circuits in Mankweng clusters with 33 schools in Lebopo circuit of which 19 of them are primary schools. This locality has enabled the researchers to collect data easily without any difficulty because the schools were in the same vicinity and there was a viable public transport between them.\n\nData was collected through semi-structured interviews, lessons observations and document analysis for the purpose of triangulation.\n\nSemi-structured interviews were used to collect data whereby more open questions were asked which enabled discussions with the participants rather than straightforward questions and answer (Foley et al., 2021). We sought consent from the three teachers to make use of a voice recorder during the interview process to ensure that we present accurate data and word-for-word to ensure that we do not misquote them (Sikhosana, 2022). Our interviews were conducted in two stages namely; pre-lesson observation and post-lesson observation to triangulate what was observed with what the teachers had said.\n\nA lesson observation schedule was used to record all observational data as an essential data gathering technique in this paper. The classroom lesson observation provided us with an opportunity to have an insider perspective of how grade 7 junior teachers conducted the practical work within their settings (Maree, 2013). The lesson observations were used to triangulate the data obtained from other techniques used such as semi-structured interviews and document analysis. With the consent from the teachers, we made used of a voice recorder during lesson observations and our lesson observation schedule to record our findings and ensure the accuracy of collected data.\n\nThe CAPS was used as a document to be analysed for the nature of this paper. The CAPS document was chosen as it provides valuable information that could assist grade 7 junior Natural Sciences teachers to understand how to conduct practical work, which practical work is applicable to grade 7 learners and how many times should the practical work be conducted (DBE, 2011).\n\nWe ensured that the paper has internal validity by making sure that the findings of the paper are based on data collected for this paper only (Sikhosana, 2022). To ensure that the study is credible and trustworthy, direct quotations from the participants were used when presenting all data collected (Tawanda & Mudau, 2023). Triangulation was used to increase validity and credibility of our research findings (Mudau & Netshivhumbe, 2022) wherein semi-structured interviews, lesson observations and document analysis were used. Pilot study conducted with one grade 7 junior Natural Sciences teacher who was not part of the main paper where both semi-structured interview, lesson observational schedules and document analysis were tested to ensure they were valid (Ntuli et al., 2022).\n\nThe data that was collected from three grade 7 junior Natural Sciences teachers was analysed and interpreted separately. Audio-recorded semi-structure interviews and lesson observation were transcribed verbatim by researchers to a word document (Mudau & Netsivhumbe, 2022). While the official CAPS document was used to as a guideline to indicate how practical work must be conducted in grade 7 Natural Sciences subject (DBE, 2015). The researchers did not correct participants’ grammatical errors to ensure that data collected from these teachers was presented accordingly and does not lose its original meaning. We analysed collected data interpretively by synthesizing, categorizing, and organizing data into themes (Nowell et al., 2017). Only data relevant to the themes were considered and assisted researchers in answering research questions and achieving the aim of this study. A typology approach was used for the process of data analysis. After collecting data, we organized the data into themes which were shaped by our research questions. We did this by immersing ourselves in the data reading to understand the whole set of data.\n\n\nResults and discussions\n\nIn this section we presented the results of three junior grade 7 Natural Sciences teachers separately. Our intentions were not to compare the cases but rather to comprehend them within their contexts which were diverse. Each case will be presented as Teacher 1, Teacher 2 and Teacher 3. The following 2 themes which assisted the researchers in answering the research questions and achieving the aim of this paper were used:\n\n1. Experiences of grade 7 junior teachers when facilitating practical work in Natural Sciences teaching and learning.\n\n2. Pedagogical approaches adopted by grade 7 junior teachers when facilitating practical work in Natural Sciences teaching and learning.\n\nPractical work is regarded as hands-on or minds on practical learning opportunities by learners (Mudau & Netshivhumbe, 2022). From the semi-structured interviews that we conducted, Teacher 1 indicated that practical work has to do with using apparatus and hands. This was evident in the statement below:\n\n“Practical work? When you are using the apparatus, hm … using apparatus. Ooh, they are using apparatus when they are using their hands.”-Teacher 1\n\nFrom the statement mentioned above, Teacher 1 indicated that practical work has to do with using apparatus and hands. However, during lesson observations, we noted that Teacher 1 did administer practical work and grouped learners in groups of five in preparation for a Natural Sciences practical activity. Sshana and Abulibdeh (2020) argued that practical work in school of science means laboratory-based experience where there are hands-on and minds-on practical learning opportunities. DBE (2011) substantiated that practical work must be integrated with theory to strengthen the concepts being taught, which was not the case with Teacher 1, as they had inadequate understanding of practical work. Wellington and Ireson (2012) indicated that practical work is recognised as an essential part of school of sciences teaching and learning. However, that was not the case with Teacher 2 as he defined practical work as:\n\n“Mmhhhh … I think practical work is just investigation to find a solution to a given problem. It is when the thing that learners are going to do practical work by themselves to find the possible solution.”-Teacher 2\n\nFrom the lesson observations, we noted that Teacher 2 used the term ‘practical work’ to refer to as any teaching and learning activity which at some point involved the learners in observing or manipulating the objects and materials that they were studying. Said (2014) also attested to the fact that practical work is a learning experience in which learners interact with materials or secondary sources of data to observe and understand the natural world. Furthermore, practical work involves all kinds of learning activities in science which provokes learners to handle and observe real objects or materials (Sshana & Abulibdeh, 2020). The observation or manipulation of objects can take place in a school laboratory but could also occurred in an out-of-school setting, such as the learners’ home or in the field (Barendsen & Henze, 2019). This was a clear indication that Teacher 2 does not have an idea of what practical work is all about.\n\nDuring the semi-structured interviews, Teacher 3 defined practical work as a teaching and learning tool of which assists learners to understand better the learning content as they are easily able to relate and put theory into practice. Teacher 3 further defined practical work as activities which involves the hands-on activities together with the minds of the learners. This was evident in the statement below\n\n“Practical work hmm … what I do understand most about practical work? is that you do things practically so, you display concrete things and not in a theoretical way. You must do it in a practical way so that the learners understand it in a better way, doing practical in your own hands.”-Teacher 3\n\nConstaninou and Fotou (2020) defined practical work as a teaching and learning transaction in which learners are given ample opportunities to practise the processes of investigation. This was similar to Teacher 3 who defined practical work as a powerful method of learning, observing and practicing hands-on activities in science. To put this in practice, Teacher 3 conducted a lesson which focused on energy and change as stipulated in the CAPS document. During this practical lesson, Teacher 3 rolled an apple across the floor and asked learners to feel the apple and also roll it on the floor; to gain a closer observation. Teacher 3 conducted this activity with an aim of developing observation skills of the learners as stated in the statement below:\n\n“Do that in practice using your own hands and minds for developmental purpose which prepares learners for the real world outside the school premises.”-Teacher 3\n\nThe handling and using of materials is a key aspect to practical activities for students (Kibga et al., 2021). As Teacher 3 rolled an apple on the floor, learners were also given chance to roll it by themselves and observed the movement of an apple until it stopped. This practical activity was an essential part in the lesson that Teacher 3 taught, as it enabled practical work during teaching and learning (Wellington & Ireson, 2012). Agreeing to that, Teacher 3 displayed an adequate understanding of what practical work entailed.\n\nDarling-Hammond et al. (2020) stated that teachers viewed practical work as illustrations and consolidations of understanding science concepts. From the lesson observations it was noted that Teacher 1 also viewed practical work as illustrations. Which focuses on developing learners’ understanding of the nature of science whereby learners are able to understand much of the concepts taught (Sshana & Abulibdeh, 2020). Furthermore, Teacher 1 viewed practical work as a holistic measure to incorporate theory into practice for a better understanding of the learning content knowledge. During lesson observations, it was noted that Teacher 1 focused much more on the content, rather than developing the process and scientific skills of the learners. These are often learner-centered, constructivist approaches that include analysis and discussion of social, technological, and environmental issues.\n\nMotlhabane (2013) indicated that teachers doubt the usefulness of practical work in relation to content comprehension. Therefore, it will be futile exercise to attempt to assist teachers without first ascertaining their perceptions on practical work. Teacher 2 viewed practical work as a process approach which was used to develop procedural skills and substantive understanding of the learners. Even if learners were in small group, this was to say that in a group of five learners, when given a task to perform, there were still those to observe while others or a group leader is performing the practical work because they have different roles to play in a group. Teacher’s views of teaching and learning science often have a pervasive influence on their classroom practices (Bantwini, 2015). Teacher 1 liked to demonstrate first to the learners the practical work especially if the theme or the topic was new to the learners. From the semi-structured interviews, we can also infer that Teacher 2 also viewed practical work as a vehicle through which learners can ascertain their different types of skills which includes among others; the scientific inquiry skill, procedural understating skills, substantive understanding skills, creative and artistic skills, independent thinking skills, and investigative skills. This was evident in the statement below when he referred to the practical work as a teaching tool to enhance teaching and learning:\n\n“Mh … I think practical work is just investigation to find a solution to a given problem. No, practical I think is the thing that learners are going to do it themselves to find the possible solution.”-Teacher 2\n\nTeacher 2 viewed practical work as an important aspect in science development. They believed that practical work is the key way for students to learn, if done accurately and appropriately. Teacher 2 also believed in illustrations and consolidation through cooperative learning. This was evident during lesson observations when Teacher 2 grouped learners to use the information collected from the practical work and represent it in a graph on the record sheet provided. They viewed practical work as the investigation of the given problem in order to find answers or solution to the problem or question; this was evident in the statement below:\n\n“Practical work can be seen as investigating a given problem or question to find a solution.: -Teacher 2\n\nThis is also emphasized by literature whereby it is indicated that practical work is perceived as a prominent and distinctive feature of science education by science teachers which enables learners to enrich their knowledge while developing a better understanding of science education (Darling-Hammond et al., 2020).\n\nTeacher 3 viewed practical work in Natural Sciences as a way of making the subject enjoyable and as a way of developing learners’ experimental skill (Ramnarain, 2014). This was evident in the statement below:\n\n“From the food that they have ate, then that is the theoretical. And there after I asked one learner to move around so for that particular learner to be able to move around it is because he has the energy in him. This energy is kinetic energy (movement) but before kinetic energy the boy was at rest possessing stored energy which is called potential energy.”-Teacher 3\n\nDudu and Vhurumuku (2012) also attested to the fact that teachers’ focus when teaching science was on the mastery of the subject matter than practical work. For many teachers, practical work provides the evidence for existing scientific knowledge and developing new knowledge (Ntuli et al., 2022). Traditionally, teachers viewed the use of practical work as illustrations and consolidations of the understanding of science concepts. Teacher 3 believed that learners must be involved in doing all the theory into practice because she believed learners learn more when they see, hear, touch, and they will never forget. Teacher 3 shown the urge that theory must be put into practice because learners learn easily and enjoy when they are doing things by themselves. From the lesson observations, we saw how they asked learners to throw the ball in the air and observe what was happening and why. The learners observed and reported back in the classroom. According to Maree (2013), observations plays an important role in collecting data as it provides researchers with an insider perspective of the participants behaviors in their natural setting. In this regard, lesson observations helped learners to develop observation skills during Teacher 3 lesson of the gravitational force. Teacher 3 also viewed practical work as integration of theory into practice to strengthen the concepts being taught (DBE, 2011). They believed that the learners needed:\n\n“To hear, see, touch the materials they are working with or investigating so as to enable them to respond more informative when recording their finding from the given practical tasks in a classroom context which will relate to the real day to day outside world experiences they would encounter in life.”-Teacher 3\n\nShulman (1986) argued that the focus of pedagogical content knowledge (PCK) is not only on the knowledge of a specific theme by a Natural Sciences teacher but also on their behaviours, reasons, and actions towards the subject content. Furthermore, Shulman (1986) stated that a presentation of PCK is simply a combination of the three facets which include: pedagogy; content; and the context. Therefore, the teacher should also know which parts of learning can be assessed and which assessment techniques should be applied (Monteiro et al., 2021). From the lesson observations, Teacher 1 conducted practical work activity which involved learners who took part in the demonstration and learners who simply observed when the demonstration was taking place. This activity gave learners an opportunity to answer questions which were posed by Teacher 1 as they were busy demonstrating and observing the procedures of cooking soup with an aim of understanding the input and output energy as stated below:\n\n“What are the input and output? … the input energy is the electrical potential energy and the output is the heat energy are we together?).”-Teacher 1\n\nHowever, from the lesson observations, not all learners were able to identify the input and output energy when cooking a soup as not all of them were involved in the observation that occurred. As a result, learners were unable to recognise and note what was observed as they were only engaged through oral questioning to attract and arouse their interest in the practical work that was done (Neubauer et al., 2019).\n\nTeacher 1 did practical work within the parameters of an explanatory model which it was explained and illustrated more during teaching. However, that was not effective as learners failed to answer the questions that Teacher 1 asked. This was evident in the statement below:\n\n“From what you have observed, how was the electrical potential energy transferred into heat energy? Come on! guys! electrical potential energy is converted into heat energy when the plate of the stove started to become hot and eventually got red, and we said you cannot create energy right? the energy can be converted, so that electrical potential energy is converted too.”-Teacher 1\n\nFrom the classroom observation, it was evident that Teacher 2 preferred conducting practical work as demonstrations. They presented various reasons for conducting practical work either as a group work or by demonstrating. Teacher 2 has a rich pedagogical content knowledge (PCK) of which their understanding of the ways for the transformation of disciplinary content into forms that are comprehensible and accessible to students (Shulman, 1986). Amongst others, they indicated that the amount of equipment as well as the disciplinary issues influences whether if it will be group work or demonstration. However, besides all the reasons Teacher 2 gave, the data showed that they generally preferred conducting demonstrations. The teacher’s PCK helps the learners to develop knowledge of basic science procedures and utilise them to engage in the science content (Miller, 2011). This was the evident that from the interviews as mentioned by Teacher 2 in the statement below:\n\n“Eyah …. hei!, mmh …., so … sometimes, eh … they have to handle the materials that we are going to use with care because some are fragile, some of the things are poisonous, so. I usually tell them that eh. You have to handle these materials with care and if they need love, they are given love first.”-Teacher 2\n\nBut during Teacher 2 lesson presentation, they did not make much of the learner involvement as stated from the interviews statement above. Only three learners used the apparatus and the rest observed and answered oral questions. This was evident in the statement below:\n\n“So, from our findings we are going to draw a bar graph on our record sheet provided to you. You know how to draw a bar graph right! So, our bar graph will have the X-axis here and the Y-axis. Then the X-axis will show us the three different types of metal whereas the Y-axis will show us the time in minutes, right! Therefore, you will draw the three bars on each metal rods verses the time taken by pins to fall. This is how you are going the represent the findings of our practical investigation on the bar graph.”- Teacher 2\n\nTeaching science successfully, teachers needed to have not only good content knowledge but also pedagogical content knowledge (Shulman, 1986). Teacher 2’s pedagogical strategy was demonstrative and investigative. This is because the student-centred pedagogy verified by the central government in China is important to learners compared to the teacher centred approach (Wang, 2011). From the interviews, Teacher 2 also stated that in subjects like Natural Sciences, theory must be put into practice, hence the involvement of the learners. Furthermore, Teacher 2’s PCK was a critical factor that influenced the teaching and learning (Karisan et al., 2013).\n\n“Yah, eh … theory and practical’s are matter related because you teach them what is going to happen or the see for themselves. They need practical and see for themselves what is happening, they give reasons of what is happening when are doing the practical part of it.”-Teacher 2\n\nThe findings from this study revealed that Teacher 2 is inclined towards a practical model of teaching. This was similar to Stoffels (2005) who indicated that some teachers preferred to conduct demonstrations than practical work during teaching and learning. The practical work conducted was affected by several factors. The large class size did not allow for the formation of groups of manageable sizes. Ten learners per group was too large a group for all learners to be directly involved with the practical work. Not all learners were therefore able to acquire skills as required from the practical work, but all learners were able to draw a bar graph representing the findings. Teacher 2 was satisfied by the availability of resources:\n\n“No … this one, eh besides, eh …, this lack of resource, I think yah. but it is also a problem that lack of resources because learners need to be grouped in manageable groups, and I think these groups could work more effectively, so … because of the lack of resources, we work with big groups and that is where lies a problem.”-Teacher 2\n\nFrom the classroom we observed that the lack of adequate supply of equipment did not allow for groups to be made smaller. Instead, the shortage of equipment led Teacher 2 to teach using a teacher-centred approach because learners were not divided into small groups but into too large group of learners thus preventing each learner in the group from being fully involved in the practical investigation. Moreover, the PCK is a procedure offering learners specific methodology or principle with the focus on how the learners learn together with the “context and resources” forming part of learning (Starkey, 2012).\n\nTeacher 3 was confined within the parameters of performance model and explanatory model (Setiadi & Irhasyuarna, 2017). They demonstrated the rolling movement to show how the transfer of chemical potential energy to kinetic energy took place. Teacher 3 also used an explanation of what happens to an object thrown in the sky but does not remain in the sky, reason being that the object would return on the earth of because of the gravitational force. Teacher 3 had adequate content knowledge and showed competency in teaching the subject matter. According to Setiadi and Irhasyuarna (2017) the explanatory model is described as a practical work that can be used to develop an understanding of the content that is being taught. According to Hurrell (2021) teachers’ procedural understanding and knowledge is the knowing how part of teaching the subject matter or a topic. This was also showcased by Teacher 3 when they explained understand why a soccer ball cannot stay in the atmosphere forever because of the gravitational force. Practical work is also used as an explanatory framework for the explanations in science.\n\n“Firstly, I have to find out if they have previous knowledge about what is to transpire and if they do have that, then I take it from there then I introduce the new topic. Like let say for example when I say: did you have some breakfast? And the learners replied “yes” and then the energy, the energy … where do you get the energy from?”-Teacher 3\n\nFrom the classroom observation we can infer that Teacher 3 conducted the practical work as demonstration, and as illustrations. This was explicitly shown when Teacher 3 explained why the objects are attracted by the force of gravity when thrown in the sky. The learners were able to observe Teacher 3 throwing the apple in the sky, while doing so, Teacher 3 asked learners as to why the apple could not remain in the sky. Learners tried to answer by saying that the initial mass of every object is attracted by the earth’s gravitational force. What Teacher 3 was doing is attested by Shulman (1986) stating that the PCK of the teacher is their understanding of how to help learners to understand specific subject matter. Teacher 3 asked:\n\n“What type of energy is in this apple? right we said we must eat so that we can have the energy in our body. Would anyone explain what potential energy is? Yes, Potential energy is the energy stored in a system. But an apple is not a system right! Potential energy is the energy that is waiting to be released. Yes, we said potential energy is the energy that is awaiting to be released right! She has eaten the apple, then the energy has been transferred.”-Teacher 3\n\nTeacher 3 used practical work in a variety of formats. These formats include among others, the recipes, open-ended investigations, skills training, teacher demonstrations to promote discussion about phenomena, to raise questions, and to solve problems.\n\n\nConclusion and recommendations\n\nIt is imperative to acknowledge that teachers need their confidence to be boosted for them to be able to conduct their day-to-day activities to the best of their ability (Sshana & Abulibdeh, 2020). The findings of this study revealed that some grade 7 junior Natural Sciences teachers were overwhelmed when facilitating practical work during teaching and learning. In addition, some of these grade 7 junior Natural Sciences teachers were unable to maintain discipline inside and outside the classroom environment when conducting practical work and demonstrations. These grade 7 junior Natural Sciences teachers had to use mechanism to cope with the demands associated with facilitation of practical work in Natural Sciences teaching and learning. Some of the approaches adopted by the grade 7 junior Natural Sciences teachers when facilitating practical work in Natural Sciences teaching and learning included group work, observations, demonstration, illustrations, projects and inquiry-based scientific investigations. It is recommended that teachers be professionally trained on how to facilitate practical work to advance the new ways of teaching and learning as advocated by per the Curriculum Assessment Policy Statement document. At the same time, teachers must be empowered with pedagogical knowledge to enable them to achieve the aims and objectives of practical work in Natural Sciences.",
"appendix": "Data availability\n\nFigshare: Teacher 1, Teacher 2 And Teacher 3 consent forms.pdf, https://doi.org/10.6084/m9.figshare.23402228.v5 (Sikhosana & Mogale, 2023a).\n\nThe project contains the following underlying data:\n\n• TEACHER 1 CONSENT FORM.pdf\n\n• TEACHER 2 CONSENT FORM.pdf\n\n• TEACHER 3 CONSENT FORM.pdf\n\nFigshare: Teacher 1, Teacher 2 and Teacher 3 interviews transcripts.pdf, https://doi.org/10.6084/m9.figshare.24352795.v1 (Sikhosana & Mogale, 2023b).\n\nThe project contains the following underlying data:\n\n• TEACHER 1 INTERVIEW TRANSCRIPT.pdf\n\n• TEACHER 2 INTERVIEW TRANSCRIPT.pdf\n\n• TEACHER 3 INTERVIEW TRANSCRIPT.pdf\n\nFigshare: Teacher 1, Teacher 2 and Teacher 3 observation schedules.pdf, https://doi.org/10.6084/m9.figshare.24352792.v1 (Sikhosana & Mogale, 2023c).\n\nThe project contains the following underlying data:\n\n• TEACHER 1 OBSERVATION SCHEDULE.pdf\n\n• TEACHER 2 OBSERVATION SCHEDULE.pdf\n\n• TEACHER 3 OBSERVATION SCHEDULE.pdf\n\nFigshare: SRQR checklist for ‘Facilitation of practical work in Natural Sciences: experiences and approaches of junior teachers’, https://doi.org/10.6084/m9.figshare.23404679.v2 (Sikhosana & Mogale, 2023e).\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 the teachers that enabled us to conduct this research at their school for their endless support.\n\n\nReferences\n\nAbdurrahman KOCA: Problems of novice teachers: Challenges vs. support. J. Edu. Black Sea Reg. 2016; 1(2).\n\nAhmed G, Faizi WUN, Akbar S: Challenges of Novice Teachers and Strategies to Cope at Secondary Level. Global Regional Review, Humanity Only. 2020; V(1): 403–416. Publisher Full Text\n\nAllchin D: From science studies to scientific literacy: A view from the classroom. Sci. Educ. 2014; 23(9): 1911–1932. Publisher Full Text\n\nAl-Naimi S, Romanowski M, Du X: Novice Teachers’ Challenges and Coping Strategies in Qatari Government Schools. Int. J. Learn. Teach. Educ. Res. 2020; 19: 118–142. Publisher Full Text\n\nAubusson P: An Australian science curriculum: Competition, advances and retreats. Aust. J. Educ. 2011; 55(3): 229–244. Publisher Full Text\n\nBantwini B: Do Teachers’ Learning Styles Influence Their Classroom Practices? A Case of Primary School Natural Science Teachers from South Africa. Int. J. Educ. Sci. 2015; 11: 1–14. Publisher Full Text\n\nBarendsen E, Henze I: Relating Teacher PCK and Teacher Practice Using Classroom Observation. Res. Sci. Educ. 2019; 49: 1141–1175. Publisher Full Text\n\nConstaninou M, Fotou N: The Effectiveness of a Must-Have Practical Work in Tertiary Life Science Education. Information. 2020; 11: 401. Contexts. International Journal of Higher Education, 6(5). 10.5430/ijhe.v6n5p26. Publisher Full Text\n\nDarling-Hammond L, Flook L, Cook-Harvey C, et al.: Implications for educational practice of the science of learning and development. Appl. Dev. Sci. 2020; 24(2): 97–140. Publisher Full Text\n\nDepartment of Basic Education: Natural sciences curriculum and assessment policy statement grade 7-9. Pretoria: Department of Basic Education; 2011.\n\nDepartment of Higher Education and Training [DHET]: Call for comments on the national scarce skills list: Top 100 occupations in demand. Government Gazette. (No. 37678); 2014. Reference Source\n\nDepartment of Education: Curriculum assessment policy statement grade 7-9 natural science. Pretoria: department of education documents; 2015.\n\nDias-Lacy SL, Guirguis RV: Challenges for New Teachers and Ways of Coping with Them. Int. J. Educ. Learn. 2017; 6(3): 265. Dias-Lacy & Guirguis, 2017. Publisher Full Text\n\nDudu WT, Vhurumuku E: Teachers’ practices of inquiry when teaching investigations: A case study. J. Sci. Teach. Educ. 2012; 23: 579–600. Publisher Full Text\n\nEsau DE, Maarman R: Re-imaging support for beginner teachers in relations to initial teacher education policy in South Africa. S. Afr. J. Educ. 2021; 41(4): 1–8. Publisher Full Text\n\nFoley G, Timonen V, Conlon C, et al.: Interviewing as a Vehicle for Theoretical Sampling in Grounded Theory. Int. J. Qual. Methods. 2021; 20: 160940692098095. Publisher Full Text\n\nHurrell DP: Conceptual knowledge OR Procedural knowledge OR Conceptual knowledge AND Procedural knowledge: Why the conjunction is important for teachers. Aust. J. Teach. Educ. 2021; 46(2): 57–71. Publisher Full Text\n\nKarışan D, Şenay A, Ubuz B: A SCIENCE TEACHER’S PCK IN CLASSES WITH DIFFERENT ACADEMIC SUCCESS LEVELS2013.\n\nKibga ES, Sentongo J, Gakuba E: Effectiveness of Hands-On Activities to Develop Chemistry Learners’ Curiosity in Community Secondary Schools in Tanzania. J. Turk. Sci. Educ. 2021; 18(4): 605–621. Publisher Full Text\n\nKivunja C, Kuyini AB: Understanding and Applying Research Paradigms in Educational2017.\n\nKozikoğlu İ, Senemoğlu N: Challenges Faced by NoviceBeginner Teachers: A Qualitative Analysis. J. Qual. Res. Educ. 2018; 6: 1–31. Publisher Full Text\n\nLodge JM, Kennedy G, Lockyer L, et al.: Understanding Difficulties and Resulting Confusion in Learning: An Integrative Review. Front. Educ. 2018; 3(49). Publisher Full Text\n\nMakoa M, Segalo L: Teachers’ Experiences of Challenges of their Professional Development. Int. J. Innov. Creativity Chang. 2021; 15(10).\n\nMaluleke M: South African schools have 5,139 teachers who are unqualified or under-qualified.2021. Reference Source\n\nMaree K: First Steps in Research. Pretoria: Van schaik; 2013.\n\nMillar R: Practical work.Osborne J, Dillon J, editors. Good practice in science teaching: What research has to say. Maidenhead: Open University Press; 2011; pp.108–134.\n\nMhlaba RE, Rankhumise MP: Mentoring novice beginner natural science teachers: a case study in the Gauteng province. S. Afr. J. Educ. 2022; 42(1). Reference Source\n\nMonteiro V, Mata L, Santos NN: Assessment Conceptions and Practices: Perspectives of Primary School Teachers and Students. Front. Educ. 2021; 6: 631185. Publisher Full Text\n\nMotlhabane A: The voice of the voiceless: Reactions on science practical work in rural disadvantaged schools. Mediterr. J. Soc. Sci. 2013; 4(14): 165–173. Publisher Full Text\n\nMotshekga A: These are the provinces with the most unqualified teachers.2021. Reference Source\n\nMudau AV, Netshivhumbe NP: Insights into the interaction and discourse in the senior phase natural sciences classroom. Int. J. Res. J. Bus. Soc. Sci. 2022; 11: 458–467. Publisher Full Text\n\nMuremela G, Kutame A, Kapueja I, et al.: Retaining scarce skills teachers in a South African rural community: an exploration of associated issues. African Identities. 2021; 21: 743–759. Publisher Full Text\n\nNeubauer BE, Witkop CT, Varpio L: How phenomenology can help us learn from the experiences of others. Perspect. Med. Educ. 2019; 8(2): 90–97. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNowell LS, Norris JM, White DE, et al.: Thematic Analysis: Striving to Meet the Trustworthiness Criteria. Int. J. Qual. Methods. 2017; 16(1): 160940691773384. Publisher Full Text\n\nNtuli TG, Nkanyani TE, Sikhosana L, et al.: Exploring Teacher Knowledge in Natural Sciences. Int. e Jour. Edu. Studies. 2022; 6: 235–245. Publisher Full Text\n\nNyoka A, DuPlooy E, Henkeman S: Reconciliation for South Africa’s education system. Elm Magazine; 2014. Reference Source\n\nRamnarain U: Teachers’ perceptions of inquiry-based learning in urban, suburban, township and rural high schools: The context-specificity of science curriculum implementation in South Africa. Teach. Teach. Educ. 2014; 38: 65–75. Publisher Full Text\n\nRoss-Hain L: Transitions in tumultuous times: Teachers’ experiences with distance learning amidst the COVID-19 pandemic2020. Reference Source\n\nSaid Z: The importance of practical activities in school science: perspectives of independent school teachers in Qatari schools.2014.\n\nSetiadi I, Irhasyuarna Y: Improvement of Model Student Learning Through the Content of Solutions Guided Discovery Buffer. IOSR Journal of Research & Method in Education. 2017; 07: 01–09. Publisher Full Text\n\nShulman LS: Those Who Understand: Knowledge Growth in Teaching. Educ. Res. 1986; 15(2): 4–14. Publisher Full Text\n\nSikhosana L: Clarifying the significance of instructional methodologies for environmental education integration. Int. J. Res. Bus. Soc. Sci. 2022; 11(7): 240–248. Publisher Full Text\n\nSikhosana L, Mogale KC: Teacher 1, Teacher 2 and Teacher 3 consent forms.pdf. figshare. Dataset. 2023a. Publisher Full Text\n\nSikhosana L, Mogale KC: Teacher 1, Teacher 2 and Teacher 3 Interview Transcripts. figshare. Dataset. 2023b. Publisher Full Text\n\nSikhosana L, Mogale KC: Teacher 1, Teacher 2 and Teacher 3 Observation Schedule. figshare. Dataset. 2023c. Publisher Full Text\n\nSikhosana L, Mogale KC: Ethics clearance certificate.pdf. figshare. Dataset. 2023d. Publisher Full Text\n\nSikhosana L, Mogale KC: Standards for Reporting Qualitative Research (SRQR). figshare. Dataset. 2023e. Publisher Full Text\n\nSouth African Democratic Teachers’ Union: SADTU says schools are no longer safe for teachers and learners.2022. Reference Source\n\nSshana ZJ, Abulibdeh ES: Science practical work and its impact on students’ science achievement. J. Technol. Sci. Educ. 2020; 10(2): 199–215. Publisher Full Text\n\nStarkey L: Teaching and Learning in the Digital Age.2012. Publisher Full Text\n\nStoffels NT: “There is a worksheet to be followed”: A case study of a science teacher’s use of learning support texts for practical work. Afr. J. Res. Sci. Math. Technol. Educ. 2005; 9(2): 147–157. Publisher Full Text\n\nSuen L, Huang H, Lee H: A Comparison of Convenience Sampling and Purposive Sampling.J. Nurs.2014; 61: 105–111. Publisher Full Text\n\nTawanda T, Mudau AV: The influence of indigenous knowledge on chemistry metacognition. F1000Res. 2023; 12: 589. Publisher Full Text\n\nWang D: The dilemma of time: Student-centered teaching in the rural classroom in China. Teach. Teach. Educ. 2011; 27: 157–164. Publisher Full Text\n\nWellington J, Ireson G: Science Learning, Science Teaching. 3rd ed.Routledge; 2012. Publisher Full Text"
}
|
[
{
"id": "236948",
"date": "15 Feb 2024",
"name": "Doras Sibanda",
"expertise": [
"Reviewer Expertise science education",
"pedagogical content knowledge",
"mixed methods research"
],
"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\nIntroduction Thank you for the opportunity to review the manuscript. I found the topic to be interesting and relevant. However, the introduction seems to focus more on teachers’ experiences and limited explanation is provided on facilitation of practical work.\nLiterature Review The literature review is on practical work. There is a need to link the introduction to the problem statement and the title. The authors need to explain why practical work is important in this study.\n\nThe Research Methods The sampling of the seven teachers needs to be clarified. There are three primary schools and does this mean that all the teachers at these schools were participants. How were the teachers recruited? There are too many research questions for the limited data set. There is a need to provide some details about the lessons observed, were the teachers teaching the same topics?\nData analysis There is a need to clarify how the themes were generated. One of the themes is on pedagogical approaches but in the literature review the theoretical framework was not clearly stated. From page 9 paragraph 2, the findings are linked to PCK. There is a need to pride a theoretical background 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? 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? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12080",
"date": "30 Aug 2024",
"name": "Lettah Sikhosana",
"role": "Author Response",
"response": "Greetings I hope you are doing well. We would like to thank you for reviewing our manuscript. Your comprehensive feedback is highly appreciated. We have gone through the manuscript and the comments that you have made, and we have managed to address the corrections as suggested which have been factored in on the new version of this manuscript. Best wishes"
}
]
},
{
"id": "240562",
"date": "15 Feb 2024",
"name": "Sam Ramaila",
"expertise": [
"Reviewer Expertise Nature of Science",
"Inquiry-based learning"
],
"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\nClarity of Purpose: The introductory statement provides a clear and concise overview of the paper's focus, which is the exploration of junior teachers' experiences and approaches in facilitating practical work in Natural Sciences during teaching and learning. Contextual Background: The mention of Grade 7 being the final year of primary school in South Africa, along with information about the age group (11 to 13 years), establishes the context for the study. This background information helps readers understand the specific educational setting and the target age group. Identification of Challenges: The researchers explicitly state that they observed \"enormous challenges\" faced by junior grade 7 teachers when preparing, designing, and conducting practical work in Natural Sciences. This identification of challenges sets the stage for the research problem and emphasizes the significance of the study. Scope and Subject Focus: The paper specifies that the focus is on practical work in Natural Sciences, providing clarity about the subject matter under investigation. This clarity is essential for readers to understand the specific context of the study. Research Design: The choice of a qualitative interpretative case study design is justified, aligning with the research objectives of exploring the experiences and approaches of grade 7 junior teachers in Natural Sciences teaching. The rationale for using an interpretative research paradigm is explained, emphasizing the understanding of lived experiences and perspectives in a social context. The two identified themes provide a clear focus for the investigation. Participants: The sampling method, purposively selecting three junior grade 7 teachers, is justified based on the aim of obtaining rich and unique data. The criteria for classifying teachers as \"junior\" (with less than 1 year of teaching experience) is specified. The demographic profile of each teacher is planned for presentation in Table 1, providing a comprehensive overview of the participants. Language and Presentation: The language used is clear and straightforward, making the information accessible to a broad audience. The sentence structure is well-organized, contributing to the overall readability of the introductory statement. Research Gap and Importance: While the challenges are highlighted, the introductory statement does not explicitly mention the existing gap in the literature or why addressing these challenges is important. Including a brief discussion on the gap in knowledge or the broader significance of the study could enhance the introduction.\nConclusion: Overall, the introductory statement effectively outlines the purpose, context, and identified challenges of the study. To further strengthen the introduction, the researchers could consider providing a brief rationale for why addressing these challenges is crucial in the field of education or how it contributes to existing knowledge.\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? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12082",
"date": "30 Aug 2024",
"name": "Lettah Sikhosana",
"role": "Author Response",
"response": "Greetings I hope you are doing well. We would like to thank you for reviewing our manuscript. Your comprehensive feedback is highly appreciated. We have gone through the manuscript and the comments that you have made, and we have managed to address the corrections as suggested which have been factored in on the new version of this manuscript. Best wishes"
}
]
},
{
"id": "240566",
"date": "05 Mar 2024",
"name": "Tshepo Mokuku",
"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 title and the abstract\nFirst, the title of the paper sounds appropriate, and reflects the gist of the article. The abstract is generally comprehensive, but could be improved by reflecting the question(s) investigated or a clearly articulated purpose, as well as the theoretical framework for the paper, which should also be reflected in the body of the paper. Not all the abstract keywords, sound central to the paper in its present version. The Paper as a Whole and its Originality\nTaken as a whole the article is consistent, and the methodology used sounds appropriate and aligned to the research questions. It sounds original and with further refinement and tightening it could contribute some valuable knowledge to the field. Research Questions and Relevant Research, and Theoretical framework The context in which the research questions were formulated is largely clear. The article is, however, limited on relevant literature based on similar studies. Such literature would help inform the discussion of the findings. In addition, the theoretical framework of the study is not distinct and clearly articulated; however, some aspect of the theory that the researchers’ applied in their analysis, seem to surface in the discussion section, and relate to concepts such as ‘explanatory model’ ‘performance model’ ‘procedural knowledge’, and ‘PCK’; these concepts could form part of the theoretical framework section of the study. Design and Execution of Methodology\nThe design of the methodology is generally well thought out, but the application could be improved to enhance dependability and interpretation of the findings. This could be achieved by providing detailed descriptions of the practical lessons conducted by individual teachers, based on individual teacher’s written lesson plans; and the lesson plans could constitute part of the documents that the researchers’ analyse. These lesson descriptions could further be enriched by the researchers’ own descriptions of the practical lessons, based on their recorded observation notes. Findings and Discussion The presentation of the results could be improved by generating more detailed textual data, as suggested above, and by analysing the data in terms of distinct themes and patterns, guided by the developed theoretical framework. Several parts of the discussion section are somewhat loose and not well substantiated. This can be corrected by inclusion of the theoretical framework section in the manuscript, to inform/guide the discussion, and by addition of descriptive textual data (in respect of the teachers’ practical lessons), to enhance the dependability and interpretation of the data. Conclusion The conclusions need to be tightened further. Grammar and Referencing Several typographical or grammatical errors were spotted, and a language focused review of the paper would certainly help improve the clarity of arguments. The researchers are also advised to pay attention to in-text referencing: there are several cases where sources seem to be unnecessarily cited or cited for no apparent reason; and cases where non-authoritative authors on the subject/concept used are acknowledged e.g. The author whose work is not methodology-based, cited against a methodology concept(s).\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? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12083",
"date": "30 Aug 2024",
"name": "Lettah Sikhosana",
"role": "Author Response",
"response": "Greetings I hope you are doing well. We would like to thank you for reviewing our manuscript. Your comprehensive feedback is highly appreciated. We have gone through the manuscript and the comments that you have made, and we have managed to address the corrections as suggested which have been factored in on the new version of this manuscript. Best wishes"
}
]
}
] | 1
|
https://f1000research.com/articles/13-15
|
https://f1000research.com/articles/13-982/v1
|
30 Aug 24
|
{
"type": "Research Article",
"title": "Detection of yellow mosaic virus resistance in Soybean (Glycine max L.) genotypes for yield and related traits",
"authors": [
"Nabila Hoque",
"Md. Ashraful Haque",
"Nabila Hoque"
],
"abstract": "Background Twenty soybean genotypes were screened for Soybean yellow mosaic virus (YMV) identification which were collected from the Genetics and plant breeding farm laboratory.\n\nMethods To evaluate genetic studies of the chosen materials, the use of a net house assay upon sap inoculation made it easier to determine the trend of the Area Under Disease Progress Curve (AUDPC) in a controlled environment. Younger leaves from these plants were gathered and used for molecular analysis.\n\nResults Six genotypes were identified with semi-resistant disease reactions. Yellow mosaic virus-resistant and susceptible soybean genotypes were distinguished using a soybean “Rsv1-h” gene-based primer pair. To discover the existence of the Rsv-1-h gene responsible for YMV resistance, a genetic diversity panel of 15 soybean genotypes was investigated with two simple sequence repeat (SSR) markers. The BARCSOYSSR_13_1115 and BARCSOYSSR_13_1173 primer sets were employed to validate the desired genes in these genotypes.\n\nConclusion The genotypes HIHS-WIHS, MINA-HAI, Shohag, G-2120, BRAGG, and BS-3 presented the major gene Rsv1-h, which is said to be essential for yellow mosaic virus resistance and can provide better yield also than other genotypes. The six soybean genotypes with the Rsv1-h gene may be resistant to mosaic virus and could be exploited as a source of improved breeding material in the future.",
"keywords": [
"soybean",
"yellow mosaic virus tolerance",
"simple sequence repeat marker",
"genetic resistance",
"Rsv1-h gene"
],
"content": "Introduction\n\nSoybean (Glycine max) is one of the significant legume crops in today’s world, whose protein content is higher than other legumes.1,2 29.7% of the total vegetable oil is produced from soybeans and its major producers are the USA, Brazil, Argentina, and China.3 As it includes 36.6 g of protein, 19.9 g of total fat, 30.2 g of carbohydrates, 9.3 g of dietary fibre, and 15.7 mg of iron per 100 g of seeds, it is nutritious for human and animal consumption.4 Soybean is cultivated in 62,870 hectares (ha) of the total cultivable area in Bangladesh, from which we get nearly 96,921 tons of soybean per year.5 However, many biotic and abiotic factors adversely affect the growth and productivity of soybeans. Among them, the soybean business faces a severe threat from the soybean yellow mosaic virus (YMV), one of the most notorious agents of yield loss among 100 viruses.6 The disease can spread from leaves to seeds during severe infestation which deteriorates the quality of the seeds.7 The economic loss caused by this disease is 30-50%; however, it may go up to as high as 80% in extreme cases.8 As YMV is a viral disease, its control through chemical or cultural practices is neither effective nor environmentally friendly. So, implementation of genetic resistance can be an ideal option for soybean yellow mosaic virus management. For such an approach to be effective, it is crucial to understand the genetic control of the disease.9 The challenge in identifying resistant soybean plants is frequently hampering the progress in the breeding of soybeans in our country. If suitable screening methods are not used, selection may result in picking plants with pseudo-resistance, as YMV is delivered by whiteflies and their distribution in the field may not be uniform.10\n\nThe generation of YMV-resistant genotypes is substantially facilitated by selection using indirect methods, such as gene linked-molecular marker(s), which may help to overcome the limitations of field screening. Microsatellites are among the most widely used molecular markers because of their high degree of polymorphism, co-dominance nature, chromosome specificity, and dependability.11 Simple Sequence Repeat markers, commonly known as SSR markers, have been utilized to locate YMV resistance gene-linked markers in soybean.12 Field screening and subsequent selection can be made easier by using these marker(s) for YMV resistance. Marker-assisted selection (MAS) is a common strategy in molecular breeding efforts for identifying YMV in soybeans.13 The species of soybeans YMV prevalent in Northern Bangladesh differed from those prevalent in Southern Bangladesh.14 For this reason, the resistance of genotypes may also vary from one region to another region depending upon the strain of the virus prevalent in our country. For the adoption of successful methods for soybean YMV resistance breeding, it is necessary to investigate and unequivocally establish the genetic control of the disease. For this reason, the present experiment was done to evaluate several soybean germplasms to identify YMV disease resistance.\n\n\nMethods\n\nThe field experiment was conducted at the experimental farm of the Department of Genetics and Plant Breeding, Bangladesh Agricultural University (BAU). It was arranged in a randomized complete block design with three replications. For molecular data analysis, soybean plants were grown in a controlled environment in the Genetics and Plant Breeding net house. The laboratory work has been carried out at the Plant Breeding Division of Bangladesh Institute of Nuclear Agriculture (BINA), Mymensingh, Bangladesh. The whole experiment was done in July 2019-June 2020.\n\nNineteen exotic germplasm and one BAU variety were collected for this experiment. In a controlled environment, younger leaves at 3 to 4 stages of soybean were rubbed with inoculation sap (viral solution) for 3 to 4 times at 3 days intervals. The inoculation sap was prepared by homogenizing young leaves with typical mosaic symptoms of virus-infected plants. Leaf inoculation was done to infect younger plants. Individual plants were scored three times for the appearance and type of symptoms at 7-, 10- and 14-days post-inoculation (dpi) with day 0 being the first inoculation date.\n\nData were recorded for morphological studies and genetic analyses of the selected soybean genotypes. Plants with no symptoms, partial symptoms and systemic mosaic symptoms were rated as 0, 1 and 2 according to the severity of the disease.15 The scoring of leaves is shown in Table 1.\n\nDisease severity data were used to compute the area under disease progress curve (AUDPC) described by Campbell and Madden (1990).\n\nWhere, n = number of successive readings,\n\nyi = disease severity at time i,\n\nti = number of days after the observation on assessment date i.\n\nAUDPC was drawn for each plant in each replicate using the mean plot disease score at each rating date.16 No vector was allowed for any kind of transmission from plant to plant. Mosquito nets were used to cover up the inoculated leaves before taking data for AUDPC.\n\nPrimer used for amplification of soybean yellow mosaic virus\n\nIn the net house experiment, leaf inoculation was allowed to infect younger plants as described by Chen et al., 2015.17 Infected leaves of earlier growth stages were collected from those soybean cultivars and were used as plant materials for molecular analysis. Two sets of primer were selected on the basis of the intensity of bands, presence of smearing, consistency with individuals and potential for population discrimination.\n\nIsolated genomic DNA was tested for quality and quantity following standard procedure. The polymerase chain reaction (PCR) amplification profile consisted of initial denaturation at 94°C for 2 minutes followed by 35 cycles consisting of denaturation, primer annealing and extension at 94°C, 60°C and 72°C, respectively, for 30 seconds to 1 minute each. PCR cocktail made with 5 μL master mixture, 1 μL of template DNA, 1 μL of each forward and reverse primer and 2 μL of Nuclease-free water, which was amplified in a standard thermocycler.\n\nAnalysis of SSR data\n\nGene diversity was calculated using Roldan-Ruiz et al. (2000)’s formula:\n\nThe presence and absence of DNA band were considered for identifying the presence or absence of the gene of interest. Polymorphism information content (PIC) values described for self-pollinated species were calculated as follows:\n\nWhere, Pij is the frequency of the jth allele for ith marker and summed over n alleles.\n\n\nResults\n\nWe did not obtain high-quality amplification from every soybean genotype. Among all polymorphic markers, polymorphism information content (PIC) was highest (0.61) in BARCSOYSSR_13_1173 and lowest (0.11) in BARCSOYSSR_13_1115 (Table 2). The list of the SSR markers and their PIC values are as follows:\n\n• BARCSOYSSR_13_1115 whose PIC value is 0.11 and major allele frequency is 0.8113\n\n• BARCSOYSSR_13_1173 whose PIC value is 0.61 and major allele frequency is 0.625\n\nBoth of these markers’ product size were 299 bp.\n\nPerformance of soybean genotypes after virus inoculation\n\nAsymptomatic plants were scored as 0; whereas plants with partial symptoms and plants with mosaic symptoms (50-80%) were scored as 1 and 2 accordingly (Figure 1).\n\nThe percent infection and AUDPC for each genotype were calculated from the scores obtained after virus inoculation at 7, 10 and 14 dpi (days post inoculation) and shown in Table 3. The high value of % infection and AUDPC indicated susceptibility, and the low value stated resistance. For this reason, MINA-HAI, Shohag, HIHS-WIHS, BS-3, BRAGG might be considered as highly resistant; Davis, Lokon, G-10180, Asset 93-19-5, G-2120 as moderately susceptible; AGS-66, TAINANS as highly susceptible (Table 3).\n\nFive genotypes were found, which showed high resistance of all. The relationship of Area under Disease progress curve (AUDPC) and %Infection in soybean genotypes is shown in Figure 2.\n\nHere, the highest percent infection (88.66%) was observed for BS-13, AGS-278, and Jayawiyaja and lowest for MINA-HAI and Asset-93-19-1 (33.33%). BS-13 and Jayawiyaja showed the highest AUDPC value (12.1) and MINA-HAI, HIHS-WIHS, and Asset-93-19-1 showed the lowest (4.8).\n\nMolecular detection using specific primer\n\nThough the disappearance and reappearance of viral symptoms often mislead us, pathological identification via AUDPC helped in the virus detection system. We emphasized Rsv1 gene identification, which has a significant role in resistant regulation in soybean. Two sets of primers were used to detect the yellow mosaic virus gene in soybean genotypes which is responsible for yellow mosaic virus resistance. The highly susceptible genotypes were cut down and SSR markers were used to detect desired genes in the 15 soybean genotypes. Individual soybean plants were screened for two simple sequence repeat (SSR) markers named BARCSOYSSR_13_1173 and BARCSOYSSR_13_1115 that flank the Rsv1 locus.\n\nFrom Figure 3, it was observed that while using the BARCSOYSSR_13_1173 SSR marker, six genotypes namely Mina-hai, Shohag (Pb-1), G-2120, HIHS-WIHS, BS-3 and BRAGG showed fragments at the expected size (299 bp) based on the simple PCR detection system. The viral resistance system is a complex mechanism that provides resistance in a semi-persistent manner, so a certain degree of resistance can be expected if the significant gene is present in a genotype. A remarkable variation was noticed in 15 genotypes (Figure 3). The PCR-based results indicated that a fragment of 300 bp was absent in most of the genotypes as the primers were gene-specific. Mina-hai, Shohag, G-2120, HIHS-WIHS, BS-3, BRAGG carried Rsv1-h gene against Soybean yellow mosaic virus (Table 3). The rest of the genotypes showed the absence of a 299-300 bp fragment, indicating that these genotypes were susceptible to SYMV. Besides this, it was observed that none of the genotypes showed fragments at the expected size (299bp) using the BARCSOYSSR_13_1115 primer.\n\n\nDiscussion\n\nViral symptom scoring was performed at 7, 10 and 14 days after inoculation of the virus. MINA-HAI, Shohag, HIHS-WIHS, BS-3, BRAGG showed resistance as their infection rate and AUDPC value were low. On the other hand, AGS-66 and TAINANS were highly susceptible because of their high value of % infection rate and AUDPC value. Davis, Lokon, G-10180, Asset 93-19-5, G-2120 was partially susceptible due to their medium level of infection rate and AUDPC value. The phenotypic performance of soybean genotypes regarding yield and yield-contributing traits partially supported this hypothesis. Stewart et al., (2013) inoculated virus to a number of genotypes and calculated % infection and AUDPC at 7, 10 and 14 dpi. They found that the resistant genotype showed 0% infection and the susceptible one showed 100% infection.15 Molecular work was also performed to ensure the scoring results. The identified resistant genotypes were expected to carry the rsv1-h gene.\n\nFor the purpose of screening individual soybean plants, we looked for two simple sequence repeat (SSR) markers that border the Rsv1 locus: BARCSOYSSR_13_1173 and BARCSOYSSR_13_1115. This marker was also utilised by Lee et al. (2013) to identify yellow mosaic virus resistance in soybean.18 The Rsv1 - h gene in cultivar Suweon 97, which confers resistance to SMVs, was found to be mapped to a 97.5-kb location (29,815,195–29,912,667 bp on chromosome 13) in the Rsv1 locus by Ma et al. (2016). This observation gave rise to further questions regarding the molecular basis of variations in resistance alleles in this specific locus.19 The dominant Rsv1 gene has been assigned to chromosome 13 (molecular linkage group F). While Rsv1 has been the subject of extensive research and discussion among scientists worldwide, as evidenced by the numerous citations, it is important to acknowledge the possibility of the existence of distinct viral strains in Bangladesh that require systematic attention in our local environment.\n\nThe six genotypes viz. Mina-hai, Shohag, G-2120, HIHS-WIHS, BS-3, BRAGG having the expected fragment of 299-303 bp using BARCSOYSSR_13_1173 primer sets which were responsible for resistance regulation against soybean yellow mosaic virus. The Rsv1 - h gene enables soybean plants to maintain better stress conditions. Zheng et al. (2014) identified two genomic-simple sequence repeat (SSR) markers, BARCSOYSSR_13_1114 and BARCSOYSSR_13_1136, which are located on either side of the RSC3Q and are associated with the Rsv1 area.20 A quantitative real-time PCR analysis of the candidate genes identified five genes that were possibly implicated in soybean YMV resistance: Glyma13g25730, 25750, 25950, 25970, and 26000. The cloning of the RSC3Q resistance candidate gene and the utilization of marker-assisted selection (MAS) in YMV resistance breeding could both benefit from these findings.\n\nFurther extensive molecular and serological studies may be helpful in understanding the Rsv1-h gene-mediated resistance regulation of soybean yellow mosaic virus.\n\nEventually, six genotypes have been found to be semi-resistant out of twenty genotypes. The genotypes HIHS-WIHS, MINA-HAI, Shohag, G-2120, BRAGG and BS-3 all have the major gene Rsv1-h, which is considered necessary for yellow mosaic virus resistance. They also have produced higher yields than other genotypes. These six soybean genotypes could be used in the future as a source of improved breeding material. During virus indexing at the field level, five genotypes showed highly susceptible expression of the YMV disease. An effort has been made in this research to identify genotypes that are resistant to YMV by using disease indexing and SSR markers. These genotypes could be used as parents in future crossing programs to develop YMV-resistant soybean cultivars through molecular breeding. The improved yellow mosaic virus-resistant genotypes could be used as a barrier against disease transmission to additional locations, perhaps increasing soybean yield in our country.\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nFigshare: Underlying and extended data for ‘Detection of yellow mosaic virus resistance in Soybean (Glycine max L.) genotypes for yield and related traits’, https://www.doi.org/10.6084/m9.figshare.25918495.v3. 21\n\nThis project contains the following underlying and extended data:\n\n• Scoring of soybean leaves\n\n• List of SSR Markers used for Soybean yellow mosaic virus identification\n\n• Performance of soybean genotypes after virus inoculation\n\n• Figure 01. Symptoms of yellow mosaic virus plants <.jpg format>\n\n• Figure 02. Relationship between Area Under Disease Progress Curve and % Infection in soybean genotypes <.jpg format>\n\n• Figure 3. The banding pattern of 15 soybean genotypes using the BARCSOYSSR_13_1173 SSR marker <.jpg format>\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 acknowledge the support of the Bangladesh Institute of Nuclear Agriculture for the molecular analysis of the soybean leaf DNA samples.\n\n\nReferences\n\nFerguson BJ, Indrasumunar A, Hayashi S, et al.: Molecular analysis of legume nodule development and autoregulation. J. Integr. Plant Biol. 2010; 52: 61–76. Publisher Full Text\n\nJensen ES, Peoples MB, Boddey RM, et al.: Legumes for mitigation of climate change and the provision of feedstock for biofuels and biorefineries. A review. Agron. Sustain. Dev. 2012; 32: 329–364. Publisher Full Text\n\nMilazzo M, Spina F, Primerano P, et al.: Soy biodiesel pathways: global prospects. Renew. Sust. Energ. Rev. 2013; 26: 579–624. Publisher Full Text\n\nSaraswat S, Sharma S: Trait association studies in soybean genotypes under post anthesis drought stress.2021.\n\nSoybean production in Bangladesh. Reference Source\n\nHartman G, Sinclair J, Rupe J: Compendium of soybean diseases. Soybean disease compendium. 1999; 37–39.\n\nHill J, Bailey T, Benner H, et al.: Soybean mosaic virus: Effects of primary disease incidence on yield and seed quality.1987.\n\nNene Y: A survey of viral diseases of pulse crops in Uttar Pradesh. A survey of viral diseases of pulse crops in Uttar Pradesh.1972.\n\nKumar B, Talukdar A, Verma K, et al.: Screening of soybean [‘Glycine max’(L.) Merr.] genotypes for yellow mosaic virus (YMV) disease resistance and their molecular characterization using RGA and SSRs markers. Aust. J. Crop. Sci. 2014; 8: 27–34.\n\nMishra N, Tripathi M, Tiwari S, et al.: Morphological and molecular screening of soybean genotypes against yellow mosaic virus disease. Legume Res. 2022; 45: 1309–1316.\n\nIjaz S: Microsatellite markers: An important fingerprinting tool for characterization of crop plants. Afr. J. Biotechnol. 2011; 10: 7723–7726.\n\nKumar B, Talukdar A, Verma K, et al.: Mapping of yellow mosaic virus (YMV) resistance in soybean (Glycine max L. Merr.) through association mapping approach. Genetica. 2015; 143: 1–10. PubMed Abstract | Publisher Full Text\n\nCollard BC, Jahufer M, Brouwer J, et al.: An introduction to markers, quantitative trait loci (QTL) mapping and marker-assisted selection for crop improvement: the basic concepts. Euphytica. 2005; 142: 169–196. Publisher Full Text\n\nTalukdar A, Harish G, Shivakumar M, et al.: Genetics of Yellow Mosaic Virus (YMV) resistance in cultivated soybean [Glycine max (L) Merr.].2013.\n\nStewart LR, Haque MA, Jones MW, et al.: Response of maize (Zea mays L.) lines carrying Wsm1, Wsm2, and Wsm3 to the potyviruses Johnsongrass mosaic virus and Sorghum mosaic virus. Mol. Breed. 2013; 31: 289–297. Publisher Full Text\n\nShaner G, Finney RE: The effect of nitrogen fertilization on the expression of slow-mildewing resistance in Knox wheat. Phytopathology. 1977; 77: 1051–1056. Publisher Full Text\n\nChen H, Zhang L, Yu K, et al.: Pathogenesis of Soybean mosaic virus in soybean carrying Rsv1 gene is associated with miRNA and siRNA pathways, and breakdown of AGO1 homeostasis. Virology. 2015; 476: 395–404. PubMed Abstract | Publisher Full Text\n\nLee WK, Kim N, Kim J, et al.: Dynamic genetic features of chromosomes revealed by comparison of soybean genetic and sequence-based physical maps. Theor. Appl. Genet. 2013; 126: 1103–1119. PubMed Abstract | Publisher Full Text\n\nMa F-F, Wu X-Y, Chen Y-X, et al.: Fine mapping of the Rsv1-h gene in the soybean cultivar Suweon 97 that confers resistance to two Chinese strains of the soybean mosaic virus. Theor. Appl. Genet. 2016; 129: 2227–2236. PubMed Abstract | Publisher Full Text\n\nZheng G-j, Yang Y-q, Ying M, et al.: Fine mapping and candidate gene analysis of resistance gene RSC3Q to soybean mosaic virus in Qihuang 1. J. Integr. Agric. 2014; 13: 2608–2615. Publisher Full Text\n\nHoque N: Detection of yellow mosaic virus resistance in Soybean (Glycine max L.) genotypes. (Datasets). 2024. Publisher Full Text"
}
|
[
{
"id": "322673",
"date": "30 Sep 2024",
"name": "Karupiah Eraivan Arutkani Aiyanathan",
"expertise": [
"Reviewer Expertise Host Plant Resistance to Pathogens",
"Biological Control of plant diseases"
],
"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\nDetection of yellow mosaic virus resistance in Soybean (Glycine max L.) genotypes for yield and related traits.\nTitle: The article title needs to be changed because the word “Detection” is not relevant to screening and identifying resistance to the virus.\nIntroduction : The importance of the YMV problem in soybeans needs to be emphasized in detail. Also, indicate the previously published information/references on molecular approaches for the confirmation of YMV resistance.\nMethods: The manuscript indicated that the virus was not confirmed as YMV before screening, so molecular confirmation is necessary. Only 20 soybean genotypes/lines were screened, which is insufficient for testing disease resistance. Additionally, no standard scoring technique was followed for the assessment of YMV, and proper references for the scoring were not cited. Resistance should be proved through vector transmission in addition to sap inoculation. Only two markers were used. More SSR markers should have been included to obtain polymorphism.\n\nResults: The presence of resistance in the genotypes should also be further confirmed by PCR using Rsv1-h gene-specific primers.\nDiscussion: The discussion does not address the relationship of YMV infection with AUDPC. A more detailed discussion with recent supporting literature is necessary.\nReferences require corrections as per Journal specification. General Comments: 1. The English language is poor and needs improvement in sentence formation. 2. Consider outsourcing (language editing) to rewrite the article. This article requires substantial revisions to become academically valid.\nTherefore, I recommend revising the manuscript to improve the language and include more relevant results and elaborate critical discussion. The mentioned shortcomings in the manuscript led me to consider it only for a \"Research Note”.\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?\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": []
},
{
"id": "338654",
"date": "23 Nov 2024",
"name": "Gabriel Madoglio Favara",
"expertise": [
"Reviewer Expertise Plant 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\nTitle: The title needs revision because the term \"yield\" is not appropriate, as this characteristic was not determined in the evaluated genotypes. Additionally, the word \"detection\" seems unsuitable and should be removed. A more fitting title could be: \"Screening for yellow mosaic virus resistance in soybean (Glycine max L.) genotypes.\" This would better reflect the focus of the study.\nIntroduction: The introduction would benefit from the inclusion of essential information regarding Yellow Mosaic Virus (YMV), such as its taxonomic classification (family and genus), particle morphology, genomic structure, and its mode of transmission via insect vectors, to provide readers with a comprehensive understanding of the virus under investigation.\nMethods The term \"controlled environment\" is somewhat general and could benefit from more specificity. Including details about key environmental parameters, such as temperature and fotoperiod, would strengthen the methodological description and aid reproducibility.\nIt is unclear whether the inoculum was tested for YMV or other viruses. The authors should clarify if the inoculum was tested for YMV and the absence of other viral infections.\nThe description of the preparation process for the \"inoculation sap\" is insufficiently detailed. It is recommended to include the specific buffer used in the preparation, as well as the proportion of plant tissue to buffer volume employed.\n\nWould be useful to specify the exact \"standard procedure\" for testing the quality and quantity of genomic DNA for reproducibility.\nPCR Protocol Details: It may be helpful to state the total reaction volume of the PCR or the concentration of each component in the cocktail for better methodological clarity.\nResults: Figure 2 is difficult to interpret, and there is no explanation for it in the text. Additionally, the legend appears to have the labels for AUDPC and virus infection reversed.\nTable 3 requires revision. For example, the genotypes BS-3 Lokon show the same values for percentage of infection and AUDPC, yet one is classified as HR (highly resistant) and the other as MS (moderately susceptible). This discrepancy should be addressed and clarified. Additionally, I disagree with the rationale suggesting that a genotype is considered resistant to YMV when the percentage of infection is as high as 50%, as seen for other genotypes in the table. The authors should reconsider the classification criteria or provide stronger justification for these classifications.\nCould the authors confirm whether the information regarding amplification in only 6 genotypes is correct? In the gel image, it is possible to observe the amplification of the 299 bp fragment in the Davis, Lokon, and SY-35 genotypes. This should be clarified to ensure consistency between the results presented in the figure and the text.\nThis study addresses an important topic regarding yellow mosaic virus resistance in soybean genotypes, but there are several areas where the methodology and presentation could be clarified. Strengthening the descriptions of experimental conditions, providing more detailed methodological information, and ensuring consistency between figures, tables, and the text would greatly improve the overall clarity and reproducibility of the study. Furthermore, the classification criteria for resistance should be more robustly justified. With these revisions, the manuscript would be significantly strengthened and offer a clearer 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? 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?\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": []
},
{
"id": "338651",
"date": "06 Dec 2024",
"name": "Wanwisa Siriwan",
"expertise": [],
"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\nTitle: \"Detection of Yellow Mosaic Virus Resistance in Soybean (Glycine max L.) Genotypes for Yield and Related Traits\" However, in the methods and results sections, the authors did not mention yield.\nIntroduction:\n1. \"As YMV is a viral disease, its control through chemical or cultural practices is neither effective nor environmentally friendly.\" What type of chemicals can control YMV? 2. Authors should include detailed information about YMV, including its genus, species, biology, etc.\nMethods: How many plants were included per replication?\nResults:\n1. The results should align with the methods to ensure consistency. 2. What was the sample size for calculating the percentage of infection? 3. For disease reactions, the authors should describe how the groups (e.g., HS, MS) were classified. 4. In Table 3, please review and correct errors related to the classification of disease reactions based on AUDPC and percentage of infection. 5. In Figure 2, the figure does not clearly represent the relationship between AUDPC and percentage of infection, leading to confusion for readers. It is recommended to modify the figure for better clarity. 6. In Figure 3, the TAINANS sample appears to show a PCR product at 299 bp as well. Additionally, the quality of the figure is poor and needs improvement.\nDiscussion: 1. The authors should discuss the integration of AUDPC and molecular markers for screening resistant species.\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? 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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "338653",
"date": "06 Dec 2024",
"name": "Shridhar Hiremath",
"expertise": [
"Reviewer Expertise Plant Pathology",
"Plant Virology",
"Plant-microbe interaction",
"Molecular Plant Pathology",
"Virus Diagnostics."
],
"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 presents an interesting investigation into the screening of soybean genotypes for resistance to Soybean yellow mosaic virus (YMV) through a combination of phenotypic evaluations and molecular analysis. The use of controlled environment assays, such as the Area Under Disease Progress Curve (AUDPC) for disease progression monitoring, adds rigor to the findings. The identification of semi-resistant genotypes and the validation of the Rsv1-h gene using SSR markers provide valuable insights into YMV resistance. Below are my detailed comments on the strengths and areas for improvement in this manuscript.\n1. The introduction has to be improved, and the taxonomic details of the YMV have to be briefly discussed. Many sentences have to be rephrased. 2. \"The species of soybeans YMV prevalent in Northern Bangladesh differed from those prevalent in Southern Bangladesh\" Here, instead of species, the \"strains\" phrase is suitable. Please do correct 3. In M&M: The detailed methodology on inoculation of viruses has to be written 4. Did the authors confirm the virus strain before performing the inoculation? If so, what primers were used for molecular characterization? This has to be discussed thoroughly! 5. The disease scale used in this study seems to be inappropriate. A standard disease scale has to be used, and a proper reference for it has to be cited. Mention if any modifications have been made to the standard disease scale. 8. M&M: Under molecular marker analysis, authors should mention the concentration of PCR components rather than the volumes of aliquots taken. This will help other researchers to reproduce the work. 9. The data presented in Table 3 is bit ambiguous. Davis has same % infection as BRAGG with less AUDPC in comparison to BRAGG but still it is considered as MS. ???How?..even Asset 93-19-1 has low % infection rate and AUDPC but still it is considered as MS?? 10. Overall the manuscript has to be revised to provide more details and clarity. The title given is inappropriate. Instead of detection screening phrase suits well and no work has been carried towards yield related trains hence it can be omitted from the title.\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? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-982
|
https://f1000research.com/articles/13-981/v1
|
30 Aug 24
|
{
"type": "Research Article",
"title": "Deep learning neural network development for the classification of bacteriocin sequences produced by lactic acid bacteria",
"authors": [
"Lady L. González",
"Isaac Arias-Serrano",
"Fernando Villalba-Meneses",
"Paulo Navas-Boada",
"Jonathan Cruz-Varela",
"Fernando Villalba-Meneses",
"Paulo Navas-Boada"
],
"abstract": "Background The rise of antibiotic-resistant bacteria presents a pressing need for exploring new natural compounds with innovative mechanisms to replace existing antibiotics. Bacteriocins offer promising alternatives for developing therapeutic and preventive strategies in livestock, aquaculture, and human health. Specifically, those produced by LAB are recognized as GRAS and QPS.\n\nMethods In this study was used a deep learning neural network for binary classification of bacteriocin amino acid sequences, distinguishing those produced by LAB. The features were extracted using the k-mer method and vector embedding. Ten different groups were tested, combining embedding vectors and k-mers: EV, ‘EV+3-mers’, ‘EV+5-mers’, ‘EV+7-mers’, ‘EV+15-mers’, ‘EV+20-mers’, ‘EV+3-mers+5-mers’, ‘EV+3-mers+7-mers’, ‘EV+5-mers+7-mers’, and ‘EV+15-mers+20-mers’.\n\nResults Five sets of 100 characteristic k-mers unique to bacteriocins produced by LAB were obtained for values of k = 3, 5, 7, 15, and 20. Significant difference was observed between using only and concatenation. Specially, ‘5-mers+7-mers+EV ’ group showed superior accuracy and loss results. Employing k-fold cross-validation with k=30, the average results for loss, accuracy, precision, recall, and F1 score were 9.90%, 90.14%, 90.30%, 90.10%, and 90.10% respectively. Folder 22 stood out with 8.50% loss, 91.47% accuracy, and 91.00% precision, recall, and F1 score.\n\nConclusions The model developed in this study achieved consistent results with those seen in the reviewed literature. It outperformed some studies by 3-10%. The lists of characteristic k-mers pave the way to identify new bacteriocins that could be valuable for therapeutic and preventive strategies within the livestock, aquaculture industries, and potentially in human health.",
"keywords": [
"Deep Learning Neural Network",
"Bacteriocin",
"Lactic Acid Bacteria",
"K-mers",
"Embedding Vectors"
],
"content": "Introduction\n\nThe emergence of antibiotic-resistant bacteria and the rise of new diseases are critical challenges that demand the search for new natural compounds with innovative mechanisms of action to support or replace current antibiotics in use.1,2 Some bacteria have the ability to produce antimicrobial proteins to inhibit or kill other nearby bacteria. This serves as a form of microbial competition and defense.3 These antimicrobial proteins, known as bacteriocins, are effective against related or similar bacteria to those that produce them, but generally do not affect other organisms such as human or animal cells.4,5 Bacteriocins have emerged as alternatives for treating urinary tract, skin, respiratory, gastrointestinal infections, among others. They provide additional or alternative treatment options compared to conventional antibiotics.6–8\n\nA summary of the classification of bacteriocins can be seen in Table 1.\n\nThis table summarizes the different classes of bacteriocins, detailing their molecular mass, properties, structural characteristics, and examples.\n\nA common type of bacteria known to produce bacteriocins is Lactic Acid Bacteria (LAB).15 Additionally, LABs are particularly intriguing due to the long history of safe use of some strains and their status as “Generally Recognized as Safe” (GRAS), along with the “Qualified Presumption of Safety” (QPS) that most LAB strains possess.16,17 Typically, LABs are either cocci or rods and encompass over 60 genera. The major genera include Aerococcus, Carnobacterium, Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Oenococcus, Pediococcus, Streptococcus, Tetragenococcus, Vagococcus, Propionibacterium, Bifidobacterium, and Weisella.2,18\n\nBacteriocins produced by LAB have gained popularity due to their promising applications in the food industry as natural preservatives. This reduces the need for adding chemical preservatives or applying physical treatments during food production.19,20 Additionally, they can be used within the pharmaceutical and medical industry, serving as therapeutic agents or alternatives to traditional antibiotics.21 Bacteriocins derived from LABs are colorless, tasteless, and odorless. Moreover, they possess several crucial metabolic traits such as strong tolerance to low pH, the ability to produce acid and aroma, protein hydrolysis, production of viscous exopolysaccharides, and resilience to high thermal stress.12,22,23\n\nOn the other hand, the development of machine learning and artificial intelligence techniques, coupled with the availability of sequenced bacterial genomes, has enabled the use of new techniques in bioinformatics. In the context of bacteriocins, employing neural networks allows for the identification of patterns in amino acid sequences (aa), providing an advantage in discovering new bacteriocins that remain uncharacterized.24,25 This research is based on the need to efficiently identify bacteriocin sequences produced by LAB,26,27 as the genetic and structural diversity of these peptides poses a challenge.28 Therefore, a deep learning neural network was developed for the binary classification of bacteriocin amino acid sequences, distinguishing between those produced by lactic acid bacteria (BacLAB) and non-BacLAB. Feature extraction using the k-mer method and vector embedding was employed.\n\n\nFields where bacteriocins can be applied to address diverse issues\n\nSome microorganisms can cause food and beverage contamination, leading to their deterioration, posing a constant concern in the food industry as it can spoil taste and cause foodborne illnesses in humans.29,30 Bacterial pathogens transmitted through food are the primary cause of food poisoning. Chemical additives have been widely used for food preservation; however, their toxicity may raise human health issues. Some of the commercially used chemical preservatives include various synthetic chemicals.31,32 Currently, there is a negative public perception towards chemical preservatives. This has led to a consumer preference for alternatives considered more “natural”.33\n\nIn response to this demand for natural preservatives, bacteriocins show significant potential for use in the food industry, aiming to prevent food spoilage and hinder disease transmission by inhibiting the growth of pathogenic bacteria.33,34 Certain LAB-derived bacteriocins, such as nisin, pediocin, enterocin, and leucocin, have been employed for this purpose.35,36 They can be used in the preservation of dairy products, meats, vegetables, sourdough bread, wine, among others.2 Furthermore, using bacteriocins as preservatives leads to the creation of tastier, less acidic, lower salt content, and higher nutritional value food products. Additionally, these bacteriocins can be used as antimicrobial films in food packaging to extend the shelf life and expiration dates of these products.37,38\n\nHowever, it’s important to note that while bacteriocins are a promising tool, their application is still under development and study, and they do not completely replace traditional antibiotics in all cases. Further research is needed to fully understand their potential and limitations.33\n\nCurrently, the growing resistance of bacterial pathogens poses a serious challenge to global public health, impacting not only humans but also animals, plants, and the environmental ecosystem.39 Drug resistance is on the rise worldwide due to the excessive and uncontrolled use of antimicrobial substances. According to the WHO, superbugs represent one of the most significant threats to public health, causing millions of deaths each year.40 It is projected that by 2060, at least 20 new types of antibiotics will be needed to effectively address the problem of bacterial drug resistance. However, developing new antibiotics involves a long and complex process, posing a significant barrier. Therefore, it is imperative to explore and develop new therapeutic strategies capable of effectively combating antibiotic-resistant microorganisms.7,18\n\nIn clinical applications, some bacteriocins have demonstrated efficacy in treating infections, especially those caused by multidrug-resistant strains. Being produced by non-pathogenic bacteria that typically colonize the human body, they are of interest in the medical field.41–43 Some identified bacteriocins applicable in the treatment of infectious diseases include nisin, lacticin, salivaricin, subtilosin, mersacidin, enterocin, gallidermin, epidermin, and fermentin.29 Furthermore, bacteriocins have been explored for potential use in treating conditions such as diarrhea, dental caries, mastitis, and cancer.44,45\n\nLivestock, comprising domestic animals raised in agricultural settings, play a crucial role in providing labor and a wide range of products such as milk, meat, eggs, hides, and leather. Maintaining livestock health and improving the economy through optimal production requires proper feeding and effective hygiene practices. However, farm animals remain susceptible to infections caused by viruses and bacteria despite these measures.46–48\n\nIn the quest to safeguard animal health on farms, novel techniques are being explored as alternatives to antibiotics. This search becomes especially relevant due to various infectious diseases caused by bacteria in cattle, including conditions like mastitis, post-weaning diarrhea, meningitis, arthritis, endocarditis, pneumonia, and septicemia. Despite this pressing need, the range of bacteriocins evaluated for maintaining livestock health is limited, primarily focusing on nisin, lacticin, garvicin, and macedocin.49–51\n\nThe application of bacteriocins in livestock food or water has ensured food safety by reducing the presence of foodborne pathogens in the gastrointestinal tract.52,53 This application of bacteriocins has not only been used to improve the productivity of cattle but also probiotic strains capable of producing bacteriocins have been explored to increase the growth rate of pigs. Furthermore, efforts have been made in the poultry industry to control Salmonella.54 Maintaining a diet with bacteriocin-producing bacteria can reduce existing populations of foodborne pathogens such as Salmonella and Escherichia coli and prevent the reintroduction of these pathogenic bacteria.52 Additionally, they can be used in other forms such as the development of intra-mammary formulations for mastitis, which act as germicidal preparations applied to cows’ udders.55,56\n\nAquatic cultures face similar challenges to livestock, dealing with potential pathogenic risks and requiring preventive measures such as various breeding techniques, vaccination, and antibiotic use.52,57 Bacteriocins function as probiotics, leveraging the interconnected ecosystem shared by animals and microorganisms within the aquatic environment. This interaction promotes probiotic competition against pathogenic bacteria, facilitating the production of inhibitory compounds. As a result, it improves water quality, strengthens the immune response of host species, and enhances species nutrition by producing additional digestive enzymes.58–60\n\nStudies involving photosynthetic bacteria like Rhodobacter sphaeroides and bacteriocins derived from Bacillus spp. have investigated their impact as probiotics on shrimp growth and digestive enzyme activity.61,62 Likewise, experiments with nutrient-enriched water using Alchem Poseidon, a blend of Bacillus subtilis, L. acidophilus, Clostridium butyricum, and Saccharomyces cerevisiae, have shown potential for preventing infections, as the administered bacteria successfully colonized both the host and the aquatic environment.63,64\n\nAmong the works carried out using deep learning neural networks to analyze large datasets and achieve accurate classification of bacteriocins is the article by Poorinmohammad et al. (2018).65 In this study, peptide sequence analysis is conducted using machine learning alongside feature selection, and a Sequential Minimal Optimization (SMO)-based classifier is developed to predict lantibiotics, achieving precision and specificity values of 88.5% and 94%, respectively.\n\nFurthermore, in the work of Yount et al. (2020),66 the BACII𝛼 algorithm was created to identify and classify bacteriocin sequences. This algorithm integrates a consensus signature sequence, physicochemical elements, and genomic patterns within a high-dimensional query tool to select peptides resembling bacteriocins. It accurately retrieved and distinguished almost all known class II bacteriocin families, achieving a specificity of 86%. In the article by Akhter and Miller (2022), a similar approach was taken, where a machine learning-based software tool was developed to extract potential features from bacteriocin and non-bacteriocin sequences, considering their physicochemical and structural properties. Support Vector Machine (SVM) and Random Forest (RF) algorithms were employed. In this article, a precision of 95.54% was achieved.67\n\nVarious methods have also been used to identify bacteriocins from bacterial genomes based on bacteriocin precursor genes or contextual genes. For instance, BAGEL68 and BACTIBASE69 are online tools that analyze experimentally validated and annotated bacteriocins, similar to the BLASTP protein search tool. These tools rely on methods that facilitate the identification of potential bacteriocin sequences based on the homogeneity of known bacteriocins. However, these similarity-based approaches often fail to detect sequences that differ from known sequences, resulting in a significant number of false negatives. This issue led to the development of the BOA software,70 which attempts to address this problem by integrating prediction tools based on the conservation of contextual genes from the bacteriocin operon. Nevertheless, they still rely on genomic searches based on homology.\n\nIn addition, the study by Nguyen et al. (2019) utilized a different technique from the previous methods by applying word embeddings of protein sequences to represent bacteriocins. This approach takes into account the amino acid order in protein sequences to predict new bacteriocins from sequences without relying on sequence similarity. This method even enables the prediction of potentially unknown bacteriocins with high probability. Overall, representing sequences with word embeddings that preserve information about the sequence order can be applied to peptide and protein classification problems where sequence similarity cannot be used.71\n\nSimilarly, in the work by Hamid and Friedberg (2019),72 word embedding was used to identify bacteriocins, representing protein sequences using Word2vec. These representations were used as inputs for various deep recurrent neural networks (RNNs) to distinguish between bacteriocin and non-bacteriocin sequences. This technique addresses challenges such as diversity among bacteriocin sequences. Meanwhile, Fields et al. (2020) developed a process for designing and testing bacteriocin-derived compounds. They employed machine learning and a filter of biophysical features to generate an algorithm that predicts bacteriocins. This involved generating characteristic sequences of 20-mers.25\n\nAdditionally, there are other works that use antimicrobial peptide (AMP) sequences. However, it’s important to note that all bacteriocins are antimicrobial peptides, but not all antimicrobial peptides are bacteriocins. For example, in the study by Li et al. (2022),73 they present a deep learning model called AMPlify for antimicrobial peptide prediction. The cross-validation results for the model achieve 91.70% accuracy, 91.40% sensitivity, 92.00% specificity, and 91.68% F1 score.\n\nSimilarly, in Wang et al. (2023),74 they developed a bidirectional short and long-term memory deep learning network called AMP-EBiLSTM with an accuracy of 92.39%. This approach employs a binary profile function and a pseudo-amino acid composition to capture local sequences and extract amino acid information. In another study, a model known as AMP-BERT was developed. This network uses a bidirectional transformer encoder (BERT) architecture to extract structural and functional information from input peptides, categorizing each input as AMP or non-AMP. Notably, this network achieved a correct prediction rate of 76% for external test sequences selected in this research.75\n\nSimilarly, a system called AMPs-Net was introduced, an algorithm designed to streamline experimentation and improve the efficiency of discovering potent AMPs. It exhibited good prediction of the antibacterial capabilities of numerous peptides, with an average accuracy ranging from 80.98% to 91.2% and precision varying from 75.77% to 94.26%.76 In the study by Gull et al. (2019), they achieved 97% accuracy for an algorithm that identifies biologically active and antimicrobial peptides.77 Similarly, in the study by Redshaw et al. (2023), a neural network was developed to predict the antimicrobial activity of sequences. It was trained on two different databases, achieving a precision result of 86-92% for one database and 72-77% for the other.78\n\nIn another work, an application used for predicting antimicrobial peptides based on properties achieved an accuracy exceeding 80% and sensitivity above 90%.79 In the study by Yan et al. (2020), a method for predicting short-length antimicrobial peptides (≤ 30 aa) is presented. Their convolutional neural network, called Deep-AmPEP30, demonstrated a 77% accuracy rate.80 Additionally, in the study by Veltri et al. (2018), a deep learning neural network using embedding vectors to reduce weights when processing sequences was developed. It was shown that antimicrobial peptides could be constructed using only nine amino acids, achieved through the k-mers method. The network achieved an accuracy of 90.55%.81\n\n\nMethods\n\nThe general flow of the method used is illustrated in Figure 1. In section a), the input of the AA sequences is shown. There are two groups: BacLAB and Non-BacLAB. Subsequently, feature extraction is performed for each sequence. Two methods were employed. In b), the use of k-mers to obtain vectors of 0s and 1s representing the presence or absence of representative k-mer groups is shown. The resulting vectors have a length of 100. Meanwhile, in c), a 128-character embedded vector is obtained by passing the sequence through an RNN. These features are concatenated in d). The resulting concatenation serves as input for the DNN in step e). Finally, in f), a prediction of the aa sequences entered into the trained model is made.\n\nThis figure illustrates the comprehensive flow of the method used to predict bacteriocin amino acid sequences in BacLAB and Non-BacLAB groups.\n\nThe AA sequences from both BacLAB and Non-BacLAB were obtained using the publicly accessible UniProt database, downloaded in xlsx format using the Excel option on the platform.82 The search on this platform was conducted using the keyword “bacteriocin.” The retrieved parameters for each bacteriocin include: Entry, Organism, Length, and Sequence. Additionally, considering the binary classification, a column was added to label the sequences. The BacLAB dataset was labeled as 1, while the Non-BacLAB sequences were labeled as 0.\n\nTo classify which sequences correspond to BacLAB and which ones to Non-BacLAB, the parameter “organism” was considered to identify the species that produce the bacteriocin. The LAB genera included for classification encompassed Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, Streptococcus, Aerococcus, Alloiococcus, Carnobacterium, Dolosigranulum, Enterococcus, Oenococcus, Tetragenococcus, Vagococcus, and Weissella.83\n\nThe decision was made to use sequences with a length of ≥ 50 AA and ≤ 2000. As a result, a total of 24,964 sequences were obtained for the BacLAB dataset. For the Non-BacLAB dataset, after length-based selection, 25,000 sequences were randomly chosen since this dataset had a larger number of sequences. This was done to avoid introducing bias in learning by favoring the class with more data. The distribution of sequences according to their lengths can be observed in Figure 2.\n\nThe curves show the correlation between the number of sequences and the number of amino acids of the BacLAB and Non-BacLAB.\n\nK-mers\n\nIn the realm of amino acid sequence processing (or biological sequences in general) using neural networks, a ‘k-mer’ refers to subsequences of length ‘k’.84 These subsequences are formed by dividing a longer sequence into specific-sized fragments, where ‘k’ represents the size of each fragment.85 For example, a k-mer of size 5 would involve splitting the sequence into all possible subsequences of length 5, as illustrated in Figure 3. The k-mer features of a set of sequences enable the discovery of hidden patterns within that sequence population. Additionally, k-mers are useful for representing sequences in a more manageable way.86\n\nOn the left side are shown the k-mers that would be obtained from a sequence if k=5 is set. On the right side the same sequence is used, but in this case k=7.\n\nAt this stage, a list of the 100 most common k-mers within the BacLAB data set was generated. For this, several values of k were selected (k=3, 5, 7, 15, and 20). The k-mers of each BacLAB sequence were generated. Once all the k-mers were obtained, the frequency of each of them was counted. The 100 k-mers with the highest frequency were selected; this was done for each value of k, resulting in five different lists.\n\nAfter compiling the lists, feature vectors of ‘0’ and ‘1’ were extracted for each sequence, both for those in the BacLAB and Non-BacLAB groups. The k-mers obtained from each sequence were compared with the list of k-mers. A ‘1’ was assigned if the listed k-mer was present in the analyzed sequence, while a ‘0’ was assigned if the k-mer was not found. This process produced a vector of length 100. Figure 4 illustrates the process.\n\nThe list of 100 selected k-mers is compared with the k-mers of the input sequence. If one of the k-mers of the sequence is found in the list, '1' is added; if it is not found, a '0' is added. This process generates a representative vector for the sequence with 100 features in length. In this example, k=5 is used.\n\nWord embeddings are numerical representations of amino acids, where each letter denoting an amino acid receives a unique and discrete value.87 Each protein is treated as a distinct input token, and the set of 20 amino acids forms a specific dictionary. Table 2 shows the abbreviations used to denote each amino acid.\n\nThis provides a quick reference for the common abbreviations used in biological and biochemical studies.\n\nFor example, for ‘A’ (Alanine), the index 1 is assigned. Consequently, in a sequence, each occurrence of ‘A’ is denoted with the value 1. Figure 5 clarifies the process of generating the index vector. If letters were to appear in the sequence that are not found in the list of amino acids, they will be represented as zero. These indices are used to encode sequences before introducing them into the neural network that generates the embedded vectors.\n\na) The index number corresponding to each aa is assigned. b) Shows how the sequence is encoded with the indices that correspond to each AA. c) Given that there can be letters or numbers in the sequence that do not exist in the aa list, a value of 0 is assigned as an index. This way, errors are avoided when processing the sequence.\n\nOnce the index-encoded vectors are obtained, the embedding vectors are extracted. To derive these features, a recurrent neural network (RNN) is applied using the Gated Recurrent Unit (GRU) cell. RNNs with GRUs can handle sequences of varying lengths due to their inherent sequential processing nature and the specific architecture of GRUs. This makes GRU-based RNNs particularly useful in applications where sequence lengths are variable, as they can efficiently handle input length variability without losing learning capacity.88–90\n\nThe embedding layer in the network acts as a lookup table or a weight matrix where each row represents, in our case, a vectorized representation of a specific amino acid.91 The number of rows is equal to the count of unique elements in the vocabulary, which is the number of amino acids plus one, including index zero reserved for a non-existent variable in the amino acid list. The number of columns represents the embedding dimension, a model hyperparameter set to 128 in this case. Consequently, the length of the embedding vector obtained is also 128 for each sequence. Normally, before training begins, the weight matrix is initialized randomly along with all the network parameters. However, for this step, a pre-trained network is used, loading the weights into the model. Figure 6 illustrates the structure of the RNN model.\n\nDifferent datasets will be used to train the neural network and determine which combination of parameters produces the best results. For the selection of k-mers, values of k=3, k=5, k=7, k=15, and k=20 will be used, as shown in Table 3.\n\nThis table presents the different k-mer values used for training the neural network.\n\nThese specific values for k were selected based on findings from existing research that identify characteristic patterns in certain families of bacteriocins. For example, class IIa bacteriocins have a distinct 5 AA motif, either YGNGV or YDNGI, often found at the N-terminal end.13,92 However, other studies describe this characteristic motif as a 7 AA sequence, such as YGNGVXC (where X can be any AA).93,94 The choice of higher k values was influenced by findings that revealed similarities in the N-terminal half of sequences spanning between 17 and 19 AAs.95 Additionally, a distinctive sequence among bacteriocins is YGNGVXCXXXXCXV, spanning 14 AAs, or alternatively, YGNGVXCXXXXCXVXWXXA, extending to 19 AAs.96,97 This characteristic amino acid pattern is known as the “pediocin box”.96\n\nTo predict amino acid sequences, a Deep Neural Network (DNN) was employed following the structure described in Jeff et al.’s article.97 This type of network was chosen for its ability to learn complex patterns and representations from data. Additionally, they can efficiently handle large datasets.98 The construction of this neural network used Python 3.10.12 in Google Colab along with several libraries: i) Pandas (RRID:SCR 018214),99 ii) Keras, iii) Scikit-learn (RRID:SCR 002577),100 iv) NumPy (RRID:SCR 008633),101 and v) Matplotlib.\n\nThe network architecture consists of four blocks. The input for each sequence is a vector, which corresponds to the concatenation of the results described in the k-mers section and the embedding features. Therefore, the length of the input depends on the number of concatenated features. In Figure 7, a representation is used where the extracted results using k-mers for k=5 and k=7, and the embedding features are concatenated. Since the result in k-mers corresponds to a vector of length 100, while the embedding features provide a vector length of 128, the input corresponds to a vector length of 328 for each sequence. The output of the neural network is the class of each sequence, where 1 denotes BacLAB and 0 represents non-BacLAB.\n\nThe model established the number of neurons in each defined layer block, with 128 neurons for the first two layers, 64 neurons for the next four layers in the second block, followed by 32 neurons for the five subsequent layers in the third block, and finally, two neurons in the last two layers in the fourth block. The number of neurons was determined based on the input parameters and the DNN architecture.102 Out of the total thirteen layers in the model (excluding input and output layers), four layers are dense, three layers are activation layers, three layers are dropout layers, two layers are normalization layers, and one layer is a flattening layer. Table 4 provides a summary of the layers in the proposed DNN model.\n\nAdditionally, among the hyperparameters used, 75 epochs were set, a batch size of 40, and a learning rate of 2.5×10-5 for the Adam optimizer. “Mean_absolute_error” was used as the loss function. For training and testing the neural network, the k-fold cross-validation technique was employed, with k=30 selected.\n\nIn this study, ANOVA test along with Tukey test was used to assess significant differences among multiple groups based on parameters of interest, including accuracy, loss, precision, recall, and F1 score. These parameters are critical for evaluating the performance of the implemented neural network.\n\nA confidence interval of 95% was selected to ensure that the differences identified between the groups are statistically significant, providing greater certainty about the conclusions drawn from the analysis. It is important to note that RStudio Cloud software was used as the statistical analysis tool to conduct these evaluations.\n\n\nResults\n\nThe lists of k-mers were obtained for values of k=3, k=5, k=7, k=15, and k=20. For each k-mer, the 100 most frequent repetitions among the sequences were selected. The list can be found in a xlsx file in the repository.103 Through k-fold cross-validation, various performance metrics of the neural network were obtained. These metrics include loss, precision, recall, F1 score, and accuracy. They were evaluated for each group with different feature concatenations. Since thirty iterations were performed for each set, Table 5 presents the metrics averaged per group.\n\nThe initial evaluation was conducted using only features extracted from EV. The results obtained for each metric demonstrate notable performance, as both precision and F1 score reached approximately 89%, while the loss function was around 10%. However, an exploration was conducted by including more features to examine if the metric percentages could be improved. Therefore, a concatenation of EV features with various k-mers was implemented.\n\nTo demonstrate if there are significant differences between the metrics of each group, an Analysis of Variance (ANOVA) was conducted for each metric. Table 6 shows the results obtained. This analysis revealed substantial differences between the groups, as the Pr(>F) values are less than α=0.05. Therefore, the null hypothesis is rejected, and the alternative hypothesis is accepted.\n\nLos parámetros de la tabla indican: Df: Grados de Libertad, Sum Sq: Suma de cuadrados, Mean Sq: Cuadrado medio, Pr(>F): Valor p.\n\nTo discern the differences between groups, a Tukey post hoc test was conducted. This test allows paired comparisons of the means of each group. Since the aim is to determine if using concatenated features yields better results than using EV exclusively. Table 7 presents the results of the Tukey test for the groups that show significant differences between using EV exclusively or the concatenation of EV with k-mers. The complete table can be found on the GitHub page.\n\nThe parameters in the table indicate: diff: difference in the means of the compared groups, lwr: lower limit of the confidence interval, upr: upper limit of the confidence interval, p adj: adjusted p-value.\n\nIn the accuracy parameter, there is a significant difference for the groups ‘3-mers + EV’, ‘5-mers + 7-mers + EV’, and ‘5-mers + EV’. These show ‘p adj’ values lower than α=0.05. The difference between the mean values of the EV group and the ‘3-mers + EV’ group in the ‘diff’ parameter yields a positive value, indicating that the results of the EV group are superior compared to ‘3-mers + EV’. Conversely, the differences of the ‘5-mers + 7-mers + EV’ and ‘5-mers + EV’ groups are negative. This indicates that using these two concatenation groups of k-mers and EV produces better accuracy results than using only EV.\n\nFor the precision parameter, the mean values of the EV group surpassed those of ‘3-mers + EV’, showing a positive difference. Similarly to accuracy, the exclusive use of EV yields superior precision. However, the groups ‘5-mers + 7-mers + EV’ and ‘5-mers + EV’ exhibited higher mean values than EV, displaying negative differences, indicating that these groups produce better precision than the exclusive use of EV. Regarding the loss parameter, significant differences were observed only between EV and the ‘EV + 5-mers + 7-mers’ group. In contrast to accuracy, the mean values of EV were higher than those of the ‘EV + 5-mers + 7-mers’ group, favoring the concatenated feature group, considering that lower loss percentages are desired in a neural network.\n\nResults for the Recall and F1 scores showed significant differences between the EV and ‘3-mers + EV’ groups for both parameters. However, in both cases, the mean values for EV outperformed ‘3-mers + EV’. These results indicate that optimal Recall and F1 scores are generated for the EV group. The Tukey test results indicated that the ‘5-mers + 7-mers + EV’ group produces the best result. The results obtained for each cross-validation fold of this group are shown in Table 8. Among the cross-validation folds of this group, fold k=22 demonstrated the best result, recording a loss of 8.500%, an accuracy of 91.471%, and a precision, recall, and F1 score of 91.000%. Due to its performance, this methodology was chosen for implementation as the model’s classifier and for incorporating the weights generated in the neural network.\n\nFigure 8 illustrates the progress of the loss and accuracy metrics during the 75 epochs of fold 22. The measurements indicated adequate convergence during training. Initially, accuracy revealed low values that progressively increased over epochs, both in training and validation (Figure 8a). In contrast, the loss was high during the initial stages of training, decreasing as the training and validation processes progressed (Figure 8b). Although attempting to use a larger number of epochs, there was no observed increase in accuracy or decrease in loss beyond the maximum level reached at epoch 70, so this parameter was set at 75, as increasing it would imply greater computational expense without any benefit.\n\nVisualization of the distributed training metrics for the classifier after 75 epochs from 22° folder, which yielded superior results by employing the concatenation of 5-mers, 7-mers and Embedding Vector.\n\nThe efficiency of the neural network was assessed using a confusion matrix. The data from the main diagonal were presented, indicating the number of correct predictions made by the model (Figure 9). A total of 732 sequences were correctly classified as non-BacLAB, while 791 were classified as true BacLAB proteins. Values below the main diagonal represent false negatives, where 39 cases were incorrectly classified as non-BacLAB. On the other hand, values above the main diagonal reflect false positives, where 103 cases were incorrectly classified as BacLAB.\n\na) The panel shows the confusion matrix for the number of sequences evaluated. b) The panel shows the confusion matrix for the number of sequences evaluated normalized to one.\n\n\nDiscussion\n\nAccording to the results of the Tukey test, the concatenation of EV and k-mers did not improve the evaluation metrics for all combinations. When comparing EV with ‘3-mers + EV’, decreases in metrics such as accuracy, precision, and loss were observed for the latter group. This could be caused by using a very short k-mer, which increases the probability of finding these k-mers in non-BacLAB sequences, resulting in more false positives. On the other hand, other combinations like ‘7-mers + EV’, ‘15-mers + EV’, ‘20-mers + EV’, ‘3-mers + 5-mers + EV’, ‘3-mers + 7-mers + EV’, ‘15-mers + 20-mers + EV’ did not show a statistically significant difference for any metric. And it was found that the ‘5-mers + 7-mers + EV’ group produces the best result.\n\nThe superior performance of the ‘5-mers + 7-mers + EV’ group can be attributed to the selected lengths of k-mers. In several studies, characteristic peptide sequences produced by lactic acid bacteria with lengths of 5 and 7 AA have been identified. Bacteriocins of subclass IIa contain the consensus sequence YGNGVXC at the N-terminal end that characterizes them. Similarly, sequences of leucocin A-UAL 187, sakacin P, and curvacin A had this same 7 AA pattern in their N-terminal region.9,95 However, other articles consider only the highly conserved part, the first 5 AA excluding the variable AA. This characteristic sequence is YGNGV or YGNGL.13,104,105 Therefore, given the precedent that certain characteristic sequences of length 5 and 7 exist among bacteriocins, this could explain why the combination of these groups yields better results.\n\nOn the other hand, the confusion matrix results showed a higher sensitivity rate than specificity. Improving specificity could be considered in future work since, for this study, higher specificity would be preferable over sensitivity. Misclassifying a non-BacLAB as BacLAB could result in losses during laboratory tests if experimental tests are to be implemented.\n\nThe model developed in this study achieved results within the range reported in the literature. However, it is essential to note that existing tools and models categorize between bacteriocins and non-bacteriocins, unlike the model proposed here, which discriminates between sequences of bacteriocins secreted by LABs or not. For example, the BAGEL software can detect putative gene clusters of bacteriocins in new bacterial genomes and has demonstrated an ROC (Receiver Operating Characteristic) analysis value of 0.99.106 Comparable to the BLASTP protein search tool, these applications use techniques to help recognize potential bacteriocin sequences by evaluating their similarity to known bacteriocins.107\n\nSimilarly, there is the Bacteriocin Operon and Gene Block Associator (BOA) software, which, unlike other models, identifies homologous gene blocks associated with bacteriocins to predict new ones.70 The Bacteriocin-Diversity Assessment software (v1.2 version) also performs similar operations. Although these studies mention achieving high accuracy, the specific percentage reached is not mentioned.108 Additionally, a comparison was made with studies using machine learning and deep learning techniques in Table 8. In this comparison, as mentioned earlier, the study presents accuracy within the existing literature, surpassing by 3% the work done by Poorinmohammad et al. (2018)65 and by 4% compared to the results obtained in Redshaw et al. (2023).78\n\nThis work also demonstrated superior performance compared to the BACII𝛼 algorithm, which identifies and classifies bacteriocin sequences. By integrating physicochemical and genomic patterns from known Class II bacteriocin families, it achieved an 86% specificity.33 Similarly, a better outcome was observed compared to using sequence composition as features. In a study where this feature was used, an accuracy of 90.55% was achieved.81 Although a similar result was observed compared to the work of Dua et al. (2020), which achieved an accuracy of 91.7%.109 However, it’s important to consider that each study uses varying amounts of data for their respective articles.\n\n\nConclusion\n\nIn this study, a deep learning neural network was developed for the binary classification of bacteriocin amino acid sequences, distinguishing whether they are produced by LAB or not. Feature extraction was performed using the k-mer method and vector embedding. Multiple experiments were conducted with ten different concatenation groups. The results included five lists of 100 characteristic k-mers of LAB-produced bacteriocins for k=3, 5, 7, 15, 20. The concatenation group ‘5-mers + 7-mers + EV’ exhibited better results. With a k-fold cross-validation of k=30, the average results for loss, precision, accuracy, recall, and F1 score were 9.900%, 90.143%, 90.300%, 90.100%, and 90.100%, respectively. Among these, fold 22 demonstrated the best results with a loss of 8.500%, precision of 91.471%, and recall, and F1 score of 91.000%.\n\nThe model developed in this study achieved consistent results with those seen in the reviewed literature. It outperformed some studies by 3-10%. The lists of characteristic k-mers pave the way to identify new bacteriocins that could be valuable for therapeutic and preventive strategies within the livestock, aquaculture industries, and potentially in human health. This information can also aid in designing and developing more effective and selective synthetic antimicrobial peptides tailored to combat specific pathogens.\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nZenodo: Deep Learning Neural Network Development for the Classification of Bacteriocin Sequences Produced by Lactic Acid Bacteria: Repository. https://doi.org/10.5281/zenodo.13279718. 103\n\nThis project contains the following underlying data:\n\nSoftware-Related Files:\n\n• BacLABNet_script.ipynb (Deep Learning Neural Network for classification of Bacteriocin Sequences)\n\n• embed_proteins.py (Recurrent Neural Network to obtained the embedding vectors)\n\n• model_I22.h5 (This file contains the trained weights of the trained model)\n\n• model_I22.json (This file contains the structure of the trained model)\n\n• rnn_gru.pt (Initial weights of the Recurrent Neural Network to obtain embedding vectors)\n\n• List_kmers.csv (List of 5-mers and 7-mers obtained from dataset after it filtered sequences shorter than 50 aa and longer than 2000 aa)\n\nFiles Used for Training, Testing, and Validation of the Neural Network\n\n• data_nonBacLAB.csv (25000 nonBacLAB amino acid sequences retrieved from Uniprot)\n\n• data_BacLAB.csv (24964 BacLAB amino acid sequences retrieved from Uniprot)\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: Deep Learning Neural Network Development for the Classification of Bacteriocin Sequences Produced by Lactic Acid Bacteria: Repository. https://doi.org/10.5281/zenodo.13279718. 103\n\n• data_BacLAB_and_nonBacLAB.csv (Combination of sequences from data_BacLAB.csv and data_nonBacLAB.csv)\n\n• all k.mers list.xlsx (Table of all k-mers obtained for k=3,5,7,15,20)\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\nYoshida M, Hinkley T, Tsuda S, et al.: Using Evolutionary Algorithms and Machine Learning to Explore Sequence Space for the Discovery of Antimicrobial Peptides. 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}
|
[
{
"id": "355994",
"date": "11 Jan 2025",
"name": "John J. Georrge",
"expertise": [
"Reviewer Expertise Rational Drug Designing",
"Novel Drug Target Identification",
"Cheminformatics",
"Bioinformatics",
"Molecular Modelling",
"Docking",
"QSAR",
"Pharmacohpore",
"Protein Engineering",
"Bioactive Peptides",
"Reverse Vaccinology",
"Artificial Intelligence",
"and Machine Learning."
],
"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\nThe research investigates a deep learning neural network for the binary classification of bacteriocin sequences produced by lactic acid bacteria (LAB). Utilizing k-mers and vector embeddings for feature extraction, the study tested ten group combinations, concluding that the concatenated features of 5-mers, 7-mers, and embedding vectors (EV) yielded superior results. With k-fold cross-validation (k=30), the model achieved notable accuracy (91.47%), precision, recall, and F1 score (91%). These results demonstrate a promising approach for identifying bacteriocins, paving the way for applications in medicine, livestock, aquaculture, and food preservation.\nWeaknesses: The abstract lacks explicit mention of the practical challenges or limitations, such as computational expense or data imbalance, which are critical for assessing the feasibility of real-world applications.\nIntroduction The study highlights the growing challenge of antibiotic resistance and the potential of bacteriocins as alternatives. LAB bacteriocins, recognized as GRAS (Generally Recognized as Safe) and QPS (Qualified Presumption of Safety), show promise for therapeutic and industrial applications. The introduction emphasizes the critical need for efficient classification methods, leveraging artificial intelligence (AI) and deep learning to address the limitations of traditional genomic tools. Existing methods like BAGEL and BLASTP rely heavily on sequence homology, often leading to false negatives. The study proposes a deep neural network as an innovative solution for identifying LAB-produced bacteriocins.\nWeaknesses: While the introduction effectively frames the problem, it does not provide sufficient detail on the limitations of existing deep learning models, nor does it address the potential biases introduced by selecting specific LAB genera.\nMethods The research employed amino acid (AA) sequences sourced from the UniProt database, filtered for lengths between 50 and 2000 AAs. LAB bacteriocin sequences were labelled as “BacLAB,” and non-LAB sequences as “Non-BacLAB.” Feature extraction was performed using k-mers of varying lengths (3, 5, 7, 15, and 20) and embedding vectors generated via a Gated Recurrent Unit (GRU)-based recurrent neural network (RNN). The concatenated features were inputs to a deep neural network (DNN) structured in four blocks with 13 layers. The model used Adam optimization, a mean absolute error loss function, and k-fold cross-validation (k=30). Statistical analyses included ANOVA and Tukey tests to validate performance metrics.\nWeaknesses: The methods section lacks clarity on how hyperparameters were tuned and does not justify the selection of specific k-mer lengths.\nResults The study identified five lists of 100 characteristic k-mers for each selected length. Performance metrics from cross-validation demonstrated that the concatenation of 5-mers, 7-mers, and embedding vectors (5-mers+7-mers+EV) achieved the best results with:\nLoss: 8.50% Accuracy: 91.47% Precision, Recall, F1 Score: 91.00%\nSignificant differences in accuracy and loss were observed between groups. The confusion matrix revealed high sensitivity but lower specificity, highlighting potential areas for improvement. Compared to other machine learning models, this study’s approach exceeded accuracy benchmarks by 3-10%.\nWeaknesses: While the results are promising, the limited scope of comparison with other algorithms leaves room for a more robust benchmarking process.\nDiscussion The superior performance of the 5-mers+7-mers+EV group is attributed to characteristic motifs in bacteriocins. The study’s findings align with known sequences in subclass IIa bacteriocins, such as YGNGVXC. The results underscore the importance of selecting appropriate k-mer lengths to balance specificity and sensitivity. However, limitations include the model’s higher false positive rate for non-BacLAB sequences, indicating room for refinement in feature selection. Additionally, comparisons with existing tools like BAGEL reveal the unique advantage of the proposed approach in distinguishing LAB-specific bacteriocins.\nWeaknesses: The discussion does not critically evaluate the computational cost and scalability of the model for larger datasets. It also overlooks the potential need for experimental validation of the predictions to confirm biological relevance.\nConclusion The study successfully developed a deep learning-based classification model for LAB bacteriocins, achieving consistent results comparable to and sometimes exceeding existing methods. The identified k-mers and embeddings offer a robust foundation for future work in therapeutic, aquacultural, and industrial applications. While promising, further specificity and practical testing improvements are essential to validate and expand the model’s utility.\nWeaknesses: The conclusion is overly optimistic and does not sufficiently address the study’s limitations, such as the reliance on publicly available datasets that may not represent all bacteriocin-producing LAB.\nReferences References were cited appropriately within the research, highlighting the breadth of prior work on bacteriocins and machine learning applications.\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": "355998",
"date": "27 Jan 2025",
"name": "Alaa Kareem Niamah",
"expertise": [
"Reviewer Expertise Bacteriocin production",
"Lactic acid Bacteria"
],
"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 Editors and Authors\n\n1-The introduction needs to be supported by some sources related to the current study, such as: refer 1 and 2 2-The aim of the study is not clear and is not mentioned in the manuscript introduction.\n3-The labeling of the x-axis in Figure 2 should be corrected.\n4-Table 2 has no meaning and should be deleted. Since the coding is known and previously included in references.\n5-Figure 6 is not clear. It should be explained better than the current situation and explain what these shapes, such as circles and arrows, mean.\n6-Table 8 should preferably be written and discussed with the results of previous references, not as in the current situation. It is not permissible to put a table containing the results of others.\n7-Figure 8 The authors did not explain what A and B mean.\n8-Figure 8 The authors did not explain what a and b mean.\n9-The conclusions are very poor. This chapter is dedicated to the conclusions of the current study, but we see that the authors have mentioned many results. This chapter should be rewritten and all the results mentioned should be deleted.\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?\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": []
}
] | 1
|
https://f1000research.com/articles/13-981
|
https://f1000research.com/articles/13-166/v1
|
08 Mar 24
|
{
"type": "Study Protocol",
"title": "Factors affecting community ambulation post-stroke: a mapping review protocol",
"authors": [
"Kanika Bansal",
"Jane Morgan-Daniel",
"Sudeshna A. Chatterjee",
"Dorian K. Rose",
"Jane Morgan-Daniel",
"Sudeshna A. Chatterjee",
"Dorian K. Rose"
],
"abstract": "Background Most stroke survivors consider community ambulation an essential but unmet goal of their recovery. Historically, interventions to enhance community ambulation have focused on improving biomechanical impairments of gait; however, recent evidence suggests that biopsychosocial and environmental factors may impact community ambulation, even beyond more obvious physical impairments. The identification of factors that pose as significant facilitators or barriers to community ambulation may serve to guide stakeholders in designing relevant and evidence-based interventions for improving community ambulation post-stroke.\n\nObjective This review aims to map the type and extent of existing evidence on the physical, biopsychosocial, and environmental factors affecting community ambulation post-stroke. Additionally, this review will describe the various methods used to examine the extent to which stroke survivors are restricted to community ambulation.\n\nMethods Nine databases will be searched including CINAHL, PubMed, and Web of Science. We will include studies published in English during or after 2001. Studies that examine physical, biopsychosocial, and/or environmental factors affecting community ambulation in ambulatory adults at least six months post-stroke will be considered for inclusion. Studies that assess general physical activity or community mobility through transportation modes other than walking will be excluded. All identified records will be collated in citation management software, followed by steps of deduplication, title/abstract screening, and full-text reviews by at least two independent reviewers. The bibliographies of the extracted studies will also be reviewed for relevant articles. The extracted studies will be analyzed, critically appraised, and presented in tabular, narrative, and evidence map formats.\n\nDiscussion The evidence gained will be used to build a framework for community ambulation, informing stakeholders to develop meaningful interventions to improve community ambulation. The mapped evidence will motivate future studies to develop holistic approaches that specifically focus on the most vital factors that influence post-stroke community ambulation.",
"keywords": [
"Real-world",
"Participation",
"Re-integration",
"Outdoor",
"Walking",
"Scoping Review"
],
"content": "Introduction\n\nStroke is a leading cause of chronic disability in the world.1 In 2019, there were more than 101.5 million stroke survivors across the globe.1 Poststroke muscle weakness and loss of voluntary motor control are associated with reduced gait speed, decreased endurance, and higher energy costs of walking. Indeed, adults post-stroke tend to spend more than 80% of their time sedentary, taking an average of 4,078 steps per day, far less than the recommended 6,500-8,500 steps per day for people with chronic disabilities.2 With advances in gait rehabilitation, 65–85% of stroke survivors regain the ability to walk short distances independently, although they are limited to safe, stable, and structured environments such as their own homes or clinics.3 More than 75% of stroke survivors consider their ability to ‘get out of the home’ as essential to very important for their recovery,4 yet only 30% of them are satisfied with their level of community ambulation.5 Community ambulation is most widely defined as “independent mobility outside the home, which includes the ability to confidently negotiate uneven terrain, private venues, shopping centers, and other spaces”.4 The ability to walk safely in the community provides stroke survivors hope for recovery, a sense of independence, and a return to pre-stroke lifestyle, and may provide increased opportunities for social connections and overall engagement in life roles.6 Participation in community ambulation may also help interrupt the commonly observed sedentary lifestyle post-stroke and may assist in reducing the risk of a second stroke.1 Collectively, evidence suggests that improving community ambulation is a major but unmet goal of post-stroke gait rehabilitation.\n\nHistorically, most post-stroke physical therapy interventions focus on improving the physical, biomechanical, and neurological aspects of walking that lead to enhanced gait outcomes in the clinic, but have limited transferability to walking in a complex community environment.7,8 However, since the emergence of the World Health Organization’s International Classification of Functioning, Disability, and Health (ICF) model in 2001, there has been a shift in focus from targeting only physical impairments to focusing on personal, environmental, and social factors impacting a person with stroke. Numerous studies have indicated that factors such as balance self-efficacy,9 motivation, social support,10 socioeconomic status, cognitive abilities,11,12 and environmental terrains13 impact community ambulation post-stroke, even beyond physical gait impairments. Recent studies indicate that interventions to improve community ambulation have not been successful unless they are accompanied by behavioral14 or social change components.6 However, thorough, and comprehensive guidance on which physical, personal, environmental, and social factors are significant facilitators or barriers to community ambulation is lacking. The multitude of factors impacting community ambulation also makes comprehensive assessment of community ambulation an ongoing challenge for clinicians.15 Currently, the measurement of community ambulation includes a wide range of assessments, such as clinical outcomes,16 self-report measures (surveys, diaries, and questionnaires),17 and records of daily stepping activity through accelerometry.18 A lack of consistent and uniform measurements of community ambulation is a major barrier to compiling results from existing clinical trials to guide future interventions.8 Identifying tools that accurately examine the extent to which stroke survivors are restricted in their community ambulation is necessary for the development of evidence-based rehabilitation.\n\nBased on the essential but unmet need to develop a comprehensive understanding of factors reported to impact post-stroke community ambulation, a mapping review methodology was deemed necessary.19 The overarching objective of this review is to map the type and extent of the physical, biopsychosocial, and environmental factors affecting community ambulation in adults with chronic stroke and to describe the various tools used to determine the extent to which stroke survivors are restricted in their community ambulation. Specifically, this review will focus on individuals at least six months post-stroke to mitigate any confounding effects of post-stroke sequalae in the acute or subacute stage as stroke survivors transition from acute in-patient rehabilitation services to their homes, get used to their ‘new normal,’ and develop resilience to live their life after stroke.10,20 Mapping reviews are subsets of scoping reviews; therefore, this project is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).19,21 The methodology is also informed by the Campbell guidance for producing evidence and gap maps, which recommends conducting critical appraisal of included studies so that both the quantity and quality of the evidence can be recorded.22\n\nPreviously, Wesselholf and colleagues conducted a systematic review focused on community mobility post-stroke, that is, accessing the community by any means of transportation, including walking, driving, bicycling, and using public transportation.23 This systematic review concluded that community mobility is severely restricted in stroke survivors and may be affected by numerous factors such as age, education, general well-being, emotional state, motor function and coordination, independence in activities of daily living, balance, endurance, and driving status.23 While community mobility can indeed occur with a wheelchair,24 community ambulation requires walking outside one’s home or clinical environment17 and, as discussed earlier, has numerous advantages for stroke survivors’ physical, mental, and social health and overall recovery.6,25 This mapping review seeks to specifically identify reported factors impacting community ambulation post-stroke, which may differ from factors influencing community access by means of transportation other than walking. We conducted a preliminary search of BioMed Central Systematic Reviews, Campbell Collaboration Library (now known as Campbell Systematic Reviews), Cochrane Database of Systematic Reviews, JBI Database of Systematic Reviews (now JBI Evidence Synthesis), and PROSPERO: International Prospective Register of Systematic Reviews (November 15, 2018) and found no current or in-progress scoping, mapping, or systematic reviews on the proposed topic of factors affecting community ambulation post-stroke.\n\n\nReview question(s)\n\nThis mapping review aims to answer the following questions:\n\n(i) Which physical, biopsychosocial, and environmental factors affect community ambulation in individuals post-stroke are reported in the literature and to what extent?\n\n(ii) What are the various tools and clinical classification models used to measure or predict post-stroke community ambulation?\n\n(iii) What does evidence suggest is the extent to which stroke survivors return to community ambulation?\n\n\nInclusion criteria\n\nThis review will consider studies that include community-dwelling individuals at least six months after their first-ever or recurrent stroke, who are at least 18 years of age and do not use a wheelchair as their primary mode of transportation. The use of assistive devices such as canes, walkers, or ankle-foot orthoses is permissible. We will exclude studies that include non-stroke participants or participants living outside their own communities, for example, studies based on inpatient rehabilitation or palliative care. Studies that include participants with and without stroke will be considered for inclusion if data pertaining to stroke survivors can be specifically extracted.\n\nThis review will consider studies that explore the concept of post-stroke community ambulation, defined as “independent mobility outside the home, which includes the ability to confidently negotiate uneven terrain, private venues, shopping centers and other public venues”.26 We will include studies that specifically assess community ambulation, that is, walking outside one’s home, through daily stepping activity or self-report questionnaires, or predict community ambulator status based on clinical outcomes such as gait speed or the Six-Minute Walk Test (6 MWT). To ensure that self-report questionnaires focus on assessing true community ambulation, at least 25% of the questions or items on the scale must assess walking activity outside one’s home.23 Studies will be excluded if they assess general physical activity levels that may not be related to walking outside one’s home such as swimming, yoga, or biking. We will also exclude studies that only assess ‘community ambulation’ through modes of mobility other than walking, such as driving, biking, or using public transportation.\n\nThis review will consider studies that quantitatively explore at least one physical (e.g., gait speed, walking endurance, balance), biopsychosocial (e.g., age, gender, race, living with spouse, self-efficacy, depression, use of assistive device), or environmental (e.g., neighborhood walkability, Area Deprivation Index) factor(s) that impact community ambulation post-stroke. Eligible studies will not be limited to any geographic location.\n\n\nMethods\n\nThis mapping review will consider quantitative study designs, such as cross-sectional, observational, case-control, prospective, and retrospective cohorts, and longitudinal studies for inclusion. In addition, any interventional (randomized or non-randomized) studies that assessed any factors associated with community ambulation at baseline measurement and mixed-methods studies will also be included in this review. Individual studies within evidence syntheses will be screened if they are not identified through the primary literature search. Qualitative studies will be excluded from the analysis owing to a lack of quantitative evidence of the association between any measured factors and community ambulation post-stroke. In mixed-methods studies, only the quantitative portion will be considered for inclusion. Case studies and case series will be excluded as they provide limited quantitative data and represent a lower level of evidence. Conference abstracts and master/PhD dissertations will be excluded unless they are subsequently published as peer-reviewed studies.\n\nA health sciences librarian (JMD) developed search strategies using research team input and conducted a literature search. The search strategy aimed to locate primary studies published in English. A test search between December 2018 and June 2019 using the CINAHL, PubMed, and PsycINFO databases was performed to identify articles on the topic. The text words contained in the titles and abstracts of relevant articles and the index terms used to describe these articles were used to develop a full search strategy that was peer-reviewed by another health sciences librarian. The following databases were selected for the final literature search because of their topic coverage in the health and social sciences: Applied Social Sciences Index and Abstracts (ProQuest), CINAHL (EBSCOHost), PEDro, Psychology and Behavioral Sciences Collection (EBSCOHost), PsycINFO (EBSCOHost), PubMed, REHABDATA (NARIC), SPORTDiscus (EBSCOHost), and Web of Science (Clarivate Analytics). During the final literature search conducted on July 14, 2023, keywords were truncated and phrase-searched, and the search strategy was translated for each database using controlled vocabulary whenever possible. The search strategy, including all the identified keywords and index terms, was adapted for each information source. The search strategy for PubMed is publicly available as Extended data27 (see data availability statement), and all search strategies are available by contacting the lead author. The bibliographies of the articles included in the review will also be screened for additional papers not located in the literature search. Handsearching will not occur, as the selected bibliographic databases will cover all key journals (Clinical Rehabilitation, Journal of Neurologic Physical Therapy, Neurorehabilitation and Neural Repair, Physical Therapy, Physical Therapy Journal, and Topics in Stroke Rehabilitation). The search will be re-run before publishing the full mapping review to ensure that the most recent articles are retrieved.\n\nArticles published on or after January 1, 2001, to the present will be included as the World Health Organization’s International Classification of Functioning, Disability, and Health, was published in 2001. During this time, healthcare professionals transitioned their focus from ‘impairment-based disease’ to ‘function-based health’. The ICF model provides a foundational framework for this mapping review as it focuses on the domains of body structure, body function, and personal factors that could affect activities and participation related to community walking.\n\nFollowing the updated literature search, all identified records will be collated and uploaded to Endnote Web [Clarivate AnalyticsTM, PA, USA] and manually de-deduplicated in preparation for screening in Covidence [Melbourne, Australia]. Following a pilot test, titles and abstracts will be screened by any two out of three independent reviewers (KB, SAC, and DKR) to assess the inclusion criteria for the review. Potentially relevant papers will be retrieved in full, and their citation details will be automatically imported into Covidence [Melbourne, Australia]. The full texts of the selected citations will be assessed in detail against the inclusion criteria by any two of the three independent reviewers (KB, SAC, and DKR). The reasons for excluding full-text papers will be recorded and reported in the mapping review. Any disagreements between the reviewers at each stage of the selection process will be resolved through discussion or by the third reviewer. The results of the search will be reported in full in the final mapping review and will be presented in a PRISMA flow diagram.28\n\nData will be extracted from the papers included in the mapping review by two independent reviewers using a data extraction tool developed by the reviewers (see Extended data - Appendix II).27 The extracted data will include specific details about participant characteristics, methods of quantifying community ambulation and the corresponding descriptive data, factors assessed and associated with community ambulation, and key findings relevant to the review questions. The draft data extraction tool will be modified and revised, if necessary, during the process of extracting data from each included paper. Modifications will be detailed in the full mapping review. Any disagreements between the reviewers will be resolved through discussion or by the third reviewer. Authors of papers will be contacted to request missing or additional data where required. The included studies will also be critically appraised using a quality assessment tool modified from the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies (see Extended Data - Appendix III).27 Critical appraisal will also be conducted by the two independent reviewers, and any conflicts will be resolved by the third reviewer.\n\nExtracted data will be presented in tabular format with a summary of the key findings from each included study. Descriptive statistics and frequency counts will be provided for the participant characteristics and tools used to assess community ambulation. To describe the extent of post-stroke community ambulation, quantifiable data will be pooled from studies that would use a homogeneous assessment tool, such as daily steps, gait speed, or community trips/day. Additionally, based on the extracted data, we will create an evidence map of all examined physical, biopsychosocial, and environmental factors affecting community ambulation post-stroke within the ICF framework. This evidence map will be color-coded to depict the importance of each factor in relation to community ambulation, as determined by the number of studies that analyzed the factors and their cumulative sample sizes. A narrative summary will accompany the tabulated and graphical results and will describe how the results relate to the review’s objectives and questions, followed by recommendations for future research based on the identified gaps in the literature.\n\n\nDiscussion\n\nThis mapping review aims to report the physical, biopsychosocial, and environmental factors affecting community ambulation post-stroke. The evidence gained will be used to build an ICF-based model of community ambulation, which will in turn inform future interdisciplinary clinicians, policymakers, and rehabilitation scientists to develop meaningful interventions to improve community ambulation amongst stroke survivors. Additionally, this review will describe the various methods used to examine community ambulation and shed light on the extent to which individuals achieve community ambulation post-stroke. Overall, the mapped evidence will motivate future studies to develop holistic approaches that specifically focus on the most vital factors that may influence community ambulation and facilitate the recovery and reintegration of stroke survivors in their communities.\n\nEthical approval was not required for this mapping review, as we will use secondary de-identified data.\n\nThe results of this mapping review will be disseminated through national and international conference presentations as well as peer-reviewed, high-impact journal publications.\n\nThis study is currently in the data extraction phase and will be followed by data analysis, synthesis, visualization, and drafting of the final manuscript.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nOpen Science Framework: Factors Affecting Community Ambulation Post-stroke: A Mapping Review Protocol (Extended Data), https://doi.org/10.17605/OSF.IO/SEMWQ. 27\n\nThis project contains the following extended data:\n\n• Appendix I: Search strategy for PubMed, conducted on December 16, 2021\n\n• Appendix II: Data extraction instrument\n\n• Appendix III: Quality Assessment Tool\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 University of Mount Union and the senior author’s indirect funding through the University of Florida for sharing the article processing cost of this publication.\n\n\nReferences\n\nTsao CW, Aday AW, Almarzooq ZI, et al.: Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation. 2023 Feb 21; 147(8): e93–e621. PubMed Abstract | Publisher Full Text\n\nFini NA, Holland AE, Keating J, et al.: How Physically Active Are People Following Stroke? Systematic Review and Quantitative Synthesis. Phys. Ther. 2017 Jul; 97(7): 707–717. PubMed Abstract | Publisher Full Text\n\nEng JJ, Tang PF: Gait training strategies to optimize walking ability in people with stroke: a synthesis of the evidence. Expert. Rev. Neurother. 2007 Oct; 7(10): 1417–1436. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLord SE, McPherson K, McNaughton HK, et al.: Community ambulation after stroke: how important and obtainable is it and what measures appear predictive? Arch. Phys. Med. Rehabil. 2004 Feb; 85(2): 234–239. PubMed Abstract | Publisher Full Text\n\nRobinson CA, Shumway-Cook A, Ciol MA, et al.: Participation in Community Walking Following Stroke: Subjective Versus Objective Measures and the Impact of Personal Factors. Phys. Ther. 2011; 91(12): 1865–1876. PubMed Abstract | Publisher Full Text\n\nBecker I, Maleka MD, Stewart A, et al.: Community reintegration post-stroke in New Zealand: understanding the experiences of stroke survivors in the lower South Island. Disabil. Rehabil. 2022 Jun 5; 44(12): 2815–2822. PubMed Abstract | Publisher Full Text\n\nRyan HP, Husted C, Lewek MD: Improving Spatiotemporal Gait Asymmetry Has Limited Functional Benefit for Individuals Poststroke. J. Neurol. Phys. Ther. JNPT. 2020 Jul; 44(3): 197–204. PubMed Abstract | Publisher Full Text\n\nBarclay RE, Stevenson TJ, Poluha W, et al.: Interventions for improving community ambulation in individuals with stroke. Cochrane Database Syst. Rev. 2015 Mar 13; 2015(3): CD010200. PubMed Abstract | Publisher Full Text\n\nDanks KA, Pohlig RT, Roos M, et al.: Relationship Between Walking Capacity, Biopsychosocial Factors, Self-efficacy, and Walking Activity in Persons Poststroke. J. Neurol. Phys. Ther. 2016 Oct; 40(4): 232–238. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOutermans J, Pool J, van de Port I , et al.: What’s keeping people after stroke from walking outdoors to become physically active? A qualitative study, using an integrated biomedical and behavioral theory of functioning and disability. BMC Neurol. 2016 Dec; 16(1): 137. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMiller A, Pohlig RT, Reisman DS: Social and physical environmental factors in daily stepping activity in those with chronic stroke. Top. Stroke Rehabil. 2021 Apr 3; 28(3): 161–169. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMiller A, Pohlig RT, Wright T, et al.: Beyond Physical Capacity: Factors Associated With Real-world Walking Activity After Stroke. Arch. Phys. Med. Rehabil. 2021 Oct 1; 102(10): 1880–1887.e1. PubMed Abstract | Publisher Full Text\n\nRobinson CA, Matsuda PN, Ciol MA, et al.: Participation in Community Walking Following Stroke: The Influence of Self-Perceived Environmental Barriers. Phys. Ther. 2013 May 1; 93(5): 620–627. PubMed Abstract | Publisher Full Text\n\nStretton CM, Mudge S, Kayes NM, et al.: Interventions to improve real-world walking after stroke: a systematic review and meta-analysis. Clin. Rehabil. 2017 Mar; 31(3): 310–318. PubMed Abstract | Publisher Full Text\n\nAlhasani R, Radman D, Auger C, et al.: Clinicians and individuals with acquired brain injury perspectives about factors that influence mobility: creating a core set of mobility domains among individuals with acquired brain injury. Ann. Med. 2021 Dec; 53(1): 2365–2379. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPerry J, Garrett M, Gronley JK, et al.: Classification of walking handicap in the stroke population. Stroke. 1995 Jun; 26(6): 982–989. PubMed Abstract | Publisher Full Text\n\nLord SE, Rochester L: Measurement of Community Ambulation After Stroke: Current Status and Future Developments. Stroke. 2005 Jul; 36(7): 1457–1461. Publisher Full Text\n\nFulk GD, He Y, Boyne P, et al.: Predicting Home and Community Walking Activity Poststroke. Stroke. 2017; 48(2): 406–411. Publisher Full Text\n\nGrant MJ, Booth A: A typology of reviews: an analysis of 14 review types and associated methodologies. Health Inf. Libr. J. 2009; 26(2): 91–108. Publisher Full Text\n\nBarnsley L, McCluskey A, Middleton S: What people say about travelling outdoors after their stroke: A qualitative study: TRAVELLING OUTDOORS AFTER A STROKE. Aust. Occup. Ther. J. 2012 Feb; 59(1): 71–78. PubMed Abstract | 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. Publisher Full Text\n\nWhite H, Albers B, Gaarder M, et al.: Guidance for producing a Campbell evidence and gap map. Campbell Syst. Rev. 2020; 16(4): e1125. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWesselhoff S, Hanke TA, Evans CC: Community mobility after stroke: a systematic review. Top. Stroke Rehabil. 2018 Apr 3; 25(3): 224–238. Publisher Full Text\n\nBöttger T, Dennhardt S, Knape J, et al.: “Back into Life-With a Power Wheelchair”: Learning from People with Severe Stroke through a Participatory Photovoice Study in a Metropolitan Area in Germany. Int. J. Environ. Res. Public Health. 2022 Aug 23; 19(17): 10465. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTowfighi A, Markovic D, Ovbiagele B: Impact of a healthy lifestyle on all-cause and cardiovascular mortality after stroke in the USA. J. Neurol. Neurosurg. Psychiatry. 2012 Feb; 83(2): 146–151. PubMed Abstract | Publisher Full Text\n\nLord SE, McPherson K, McNaughton HK, et al.: Community ambulation after stroke: how important and obtainable is it and what measures appear predictive? Arch. Phys. Med. Rehabil. 2004 Feb; 85(2): 234–239. PubMed Abstract | Publisher Full Text\n\nBansal K, Morgan-Daniel J, Chatterjee SA, et al.: Factors Affecting Community Ambulation Post-stroke: A Mapping Review Protocol (Extended Data).2024 Jan 23. 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: n71. Publisher Full Text"
}
|
[
{
"id": "275040",
"date": "29 May 2024",
"name": "Timothy Hanke",
"expertise": [
"Reviewer Expertise Community mobility in persons' post-stroke",
"balance and falls in community-dwelling older adults."
],
"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 intend to conduct a scoping (mapping) review with the purpose to report the physical, biopsychosocial, and environmental factors affecting community ambulation in persons' post-stroke. The topic is timely, relevant, and there will be an interested readership from any number of healthcare professions.\n\nThe introduction is well-written, logical, and provides sufficient evidence for the need for this mapping review.\n\nThe study design is robust and includes the relevant methodology. The search strategy, databases/search terms are appropriate. Whether or not the grey literature is being used was addressed. The data extraction process is described. Covidence is being used. There are safeguards by using pairs of reviewers and a third for addressing any discrepancies. Critical appraisal will be conducted. As such, methods are adequately described.\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": []
},
{
"id": "299999",
"date": "23 Jul 2024",
"name": "Ahmad Sahely",
"expertise": [
"Reviewer Expertise Stroke rehabilitation",
"mobility",
"community",
"mixed 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 topic being discussed in the review is very important to inform future research in the field about factors affecting stroke survivors' ambulation in the community. The stated rationale is reasonable to reviewing current literature and synthesise evidence that can enlighten future interventions.\n\nHere are some comments to consider:\n- Is there any reason for including only individuals who are at least 6 months post-stroke, there might be some eligible participants less than 6 months with experience of ambulation in the community after discharge for sub-acute care.\n- The study cited down provides some perspectives on the topic. You might include it in you review if eligible or discuss factors affecting ambulation in the community in the discussion section.\n- Consider inclusion of qualitative/mixed methods studies as they can provide rich data from patients' perspectives about their experience of ambulation in the community.\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": [
{
"c_id": "12260",
"date": "29 Aug 2024",
"name": "Kanika Bansal",
"role": "Author Response",
"response": "Author response to reviewer comments: Comment: Is there any reason for including only individuals who are at least 6 months post-stroke? There might be some eligible participants less than 6 months with experience of ambulation in the community after discharge from sub-acute care. Response: Thank you for this comment. We decided to include only individuals who are at least 6 months post-stroke because stroke is a life-altering medical condition, not only for the patient but also for their family members.1 During the first six months, patients typically undergo multiple rehabilitative and medical appointments as they adjust to their new normal.2 The factors impacting community ambulation during the acute to subacute stages may not be relevant for the rest of their lives as stroke survivors.3 Six months post-stroke is considered the chronic phase, and from this stage onward, the factors affecting community ambulation may be influenced by multiple physical, personal, and psychosocial aspects, rather than just the acute effects of the stroke.4 Therefore, we chose to examine the factors associated with community ambulation only in individuals who are at least 6 months post-stroke. Comment: The study cited below provides some perspectives on the topic. You might include it in your review if eligible or discuss factors affecting ambulation in the community in the discussion section. (https://www.tandfonline.com/doi/full/10.1080/09638288.2022.2028019#abstract) Response: Thank you for sharing this impressive research. We will certainly consider including it in our discussion of the full mapping review. I agree that self-management is key to long-term and sustainable improvement in mobility post-stroke. Comment: Consider inclusion of qualitative/mixed methods studies as they can provide rich data from patients' perspectives about their experience of ambulation in the community. Response: Thank you for bringing this point up. We agree that patients’ perspectives on their experiences with community ambulation can provide valuable information to clinicians and stakeholders. However, our aim was to present the factors examined in community ambulation post-stroke specifically in studies that measured community ambulation through clinical outcomes, daily steps, or questionnaires. As qualitative studies may or may not measure community ambulation, many would be excluded based on our criteria. Furthermore, we plan to present the most commonly examined factors affecting community ambulation in a ‘traffic light’ format that highlights the frequency of each factor. This will include the number of studies that examined the factor and the total number of individuals for whom the factor was or was not statistically associated with community ambulation, using a color scheme: green (frequently associated), orange (mixed evidence), and red (frequently not associated).5 Given the aims of this mapping review, including qualitative studies may not do justice to the data presented. Nonetheless, we will acknowledge the lack of inclusion of qualitative studies as a limitation in our full mapping review. We will also consider conducting a separate qualitative mapping review in the future to specifically address patient perspectives on community mobility post-stroke, which may complement our current quantitative mapping review. References used in the response: 1. Lutz BJ, Young ME, Cox KJ, Martz C, Creasy KR. The Crisis of Stroke: Experiences of Patients and Their Family Caregivers. Top Stroke Rehabil. 2011;18:10.1310/tsr1806-786. 2. Ances BM, D’esposito M. Review Article: Neuroimaging of Recovery of Function after Stroke: Implications for Rehabilitation. Neurorehabil Neural Repair. 2000;14:171-179. 3. Mahendran N, Kuys SS, Brauer SG. Recovery of ambulation activity across the first six months post-stroke. Gait Posture. 2016;49:271-276. 4. Grefkes C, Fink GR. Recovery from stroke: current concepts and future perspectives. Neurol Res Pract. 2020;2:17. 5. Novak I, Morgan C, Fahey M, et al. State of the Evidence Traffic Lights 2019: Systematic Review of Interventions for Preventing and Treating Children with Cerebral Palsy. Curr Neurol Neurosci Rep. 2020;20:3."
}
]
}
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https://f1000research.com/articles/13-166
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https://f1000research.com/articles/13-526/v1
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22 May 24
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{
"type": "Systematic Review",
"title": "Exploring the Potential for Tuition-Free Higher Education in South Africa: A Scoping Review",
"authors": [
"Tlotlo Ramasu",
"Grace Kanakana-Katumba",
"Grace Kanakana-Katumba"
],
"abstract": "The debate on tuition-free higher education has raged in South Africa since the #FeesMustFall protests at South African universities in 2015 and 2016. The government responded with a tuition-free education policy targeting students from households earning less than R350 000. However, the question remains can South Africa sustain a tuition-free education policy given its developing nation status and the levels of its GDP? This article sought to assess the feasibility of tuition-free higher education for all in South Africa. A scoping review was used, and fifteen articles about tuition-free higher education feasibility in South Africa were reviewed. The choice of the scoping review was due to the need for an understanding of the current state of play in research on the feasibility of tuition-free higher education in South Africa. The results suggest that tuition-free higher education for all is not feasible in South Africa. There seems to be a consensus that South Africa lacks the resources to finance tuition-free higher education for all. Tuition-free higher education is also viewed as a regressive tax on the poor given that the majority of students in higher education institutions come from middle and upper-income households. However, it is important to note that a distinction is drawn between tuition-free higher education for all and tuition-free higher education for the poor and academically deserving. The latter seems to receive support with some viewing it as a moral imperative in an unequal society such as South Africa’s. It is recommended that future studies approach the issue from an empirical standpoint whereby the GDP levels are assessed against higher education funding.",
"keywords": [
"Free education",
"Gross Domestic Product",
"Household Income",
"Higher Education",
"South Africa."
],
"content": "Introduction\n\nFor most students, the monetary costs of attending university, college and other higher education institutions are becoming prohibitive. In South Africa, the average cost of higher education is R55 900 per year (Mafilika, 2023), while the average annual gross salary in South Africa is R303 648 (Davis, 2023, Statistics South Africa (StasSA, 2023a, b). Housing and living costs add an extra burden on students. The result is that those from poor households and historically disadvantaged communities cannot afford to attend university (Chiramba & Ndofirepi, 2023). Some countries have resorted to offering loans to students to make it easier for them to afford education. However, this has resulted in students being saddled with high levels of debt, which tend to adversely impact other aspects of life, such as family formation and home ownership (Beal et al., 2019; Goldrick-Rab & Steinbaum, 2020; Velez et al., 2019).\n\nTo ensure access to education for all, some countries have instituted policies that ensure education is free for all citizens and in some cases for international students (de Gayardon, 2019). The majority of countries with free education systems up to higher education levels are in the developed world such as Austria, Belgium, Brazil, Cyprus, Czech Republic, Denmark, Egypt, Finland, France, Germany, Greece, Hungary, Iceland, Italy, Luxembourg, Malta, Norway, Panama, Poland, Saudi Arabia, Sweden, Spain, Slovenia, Switzerland, Slovakia, Turkey and Uruguay (Chang, 2020; Erudera, 2023). In these countries free education is publicly funded, meaning taxes are the main source of funding (Hügle, 2021).\n\nIn 2015, South Africa experienced mass protests by students under the banner of #FeesMustFall (Ntombana et al., 2023). The protests started after the University of the Witwatersrand proposed a fee increase for the 2016 academic year. This was followed by protests in all government-funded universities. These protests birthed the demand for free higher education. This was in recognition of the fact that the South African education system was failing to cater for the needs of the historically marginalized and oppressed. On 16 December 2017 President Jacob Zuma surprised the country by announcing the introduction of tuition-free education at the higher education level. The announcement indicated that those in households with a combined income of less than R350 000 would be funded by the government (Department of Higher Education and Training (DHET), 2018). While the announcement was greeted with jubilation among the poor and working class, some experts raised the issue of the capability of the government to fund the system (Hlaka & Sefoka, 2022; Mdepa, 2022). Scepticism of the success of the new policy also arose due to the failures experienced with the National Student Financial Aid Scheme (NSFAS) loan system. The NSFAS loan system was designed to provide assistance to impoverished students. However, the loan faced challenges with some deserving students failing to access the loan and with low repayment rates (Ntombana et al., 2023).\n\nEducation plays an important role in national development (Kioupi & Voulvoulis, 2019). As a developing nation, South Africa is in need of an educated workforce. South Africa is faced with high levels of income inequality with a Gini coefficient of 0.67 which is the highest in the world (Friderichs, 2021). Education can play a role in bridging the gap between the wealthy and the poor. South Africa also faces the challenge of a high unemployment rate with a recorded 31.9% unemployment rate (StatsSA, 2023b). With many of the unemployed lacking skills, education can play a role in improving their employability. The introduction of free higher education for the poor was done with the belief that education would bring about equality as those formally marginalized would be able to participate in higher education resulting in gainful employment that would improve their economic conditions (DHET, 2018). However, South Africa is still a developing country and faces a myriad of challenges which demand the attention and resources of the government thus free education might impact other government programs.\n\nSouth Africa’s GDP is currently recorded at US$405 billion dollars, or US$6766 per capita (World Bank, 2022a). In comparison to other countries in the developed world offering free education, South Africa has low levels of GDP per capita. For example, Denmark has a GDP of US$ 400 billion, US$67 790 per capita (World Bank, 2022b). The average GDP per capita in Europe, a significant proportion of European countries that offer free education, is above US$37 430 (World Bank, 2023). The different economic realities those in the developed world find themselves and those faced by South Africa raise the question of whether South Africa is suited and prepared for free education in the long term. The issue of tuition-free higher education has been emotive with both sides, proponents and opposers, coming up with arguments that seem legitimate. To get a clear understanding of the issue a review of literature is warranted. Thus the is a need for a scoping review to have a clear understanding of what research studies indicate on the subject. The article seeks to assess if South Africa is able to sustain free education funding in the long term given the level of its GDP.\n\n\nLiterature review\n\nHigher education as a public good?\n\nA major point of contention between those who are pro-free education and those against has been whether education is a private good or public good (Tilak, 2008; Williams, 2016). Those who argue that education is a private good point to the many benefits that accrue to individuals due to being educated, while those who argue it is a public good consider education as key to society’s betterment and thus serve the public interest (Marginson, 2007). In Nordic countries where an economic and social model has been developed towards the upliftment of society as a whole, education is considered a public good thus they have adopted tuition-free education (Antikainen, 2016). Public goods are described as non-rivalrous and non-excludable (Marginson, 2011; Samuelson, 1954). Consumption of non-rivalrous goods does not lead to their exhaustion while non-excludable goods have their benefits extending beyond the consumer (Williams, 2016). It has been argued that education does not fully meet the characteristics of non-rivalry and non-excludability (Marginson, 2018). Entry into top higher education can be rivalrous due to limited spaces and the benefits of education do accrue to individuals making them excludable (Nixon, 2017). However, education has been noted to have benefits for society as a whole thus investment in education can be for the “public good” (Marginson, 2018). South Africa’s cost-sharing model whereby the government contribute a share and individuals contribute a share as well is borne out of the idea that higher education generates both private good and public good (De Jager & Baard, 2019).\n\nHigher education is a right?\n\nProponents of tuition-free higher education argue that education is a right thus the state has a role in ensuring that those who wish to be educated are accommodated (Burke, 2013; Gilchrist, 2018). This points to the state working towards removing all obstacles for those who want to participate in higher education. For some students, tuition fees can be an obstacle. Education can be viewed as a social right that should be afforded to every citizen for the betterment of society as a whole (Lee, 2013).\n\nPromotion of equality\n\nIn a world increasingly marked by inequality, with the rich increasingly becoming richer while the poor become poorer, education is regarded as a promoter of equality (Li et al., 2022). Proponents of free education call for equality in access to higher education as a cure to economic, and social inequality (Dias, 2015; Sá & Serpa, 2022). Thus the call for all students to have equal opportunities in accessing education despite their social and economic background, religion, gender, race, and other differentiating factors. Education is considered to be human capital and studies have indicated that improving the human capital of a nation can lead to economic growth (Gyimah-Brempong et al., 2006). Improvements in a nation’s human capital can lead to improved productivity and better technologies (Abel et al., 2012; Baharin et al., 2020). Education also has other benefits for the public such as better health, improved workforce flexibility, increased government tax revenues and higher consumption (Bloom et al., 2006; de Gayardon, 2019; Vossensteyn, 2009).\n\nHigher education in South Africa\n\nIt would not be proper to discuss South Africa’s education systems without mentioning the Apartheid Era. It can be argued that some of the inequalities in the current education system are a result of Apartheid-era policies that discriminated against large sections of the population (Mekoa, 2018). The advent of democracy in 1994 brought about a new government which focused on making education accessible for the population as a whole (Mzangwa, 2018).\n\nFunding for public higher education institutions in South Africa flows from three main sources; government grants, student tuition and other fees, and other private income which can be in the form of donations (Steyn & De Villiers, 2007; Wangenge-Ouma & Cloete, 2008). According to Khuluvhe and Netshifhefhe (2021), government grants constitute 42% of the source of funds for public higher education, while student tuition and other fees contribute 33%, and other private income contributes 25% each. This indicates the massive role the government has in the funding of public higher education institutions.\n\nIn comparison to other developing countries South Africa’s spending on education is not particularly remarkable; the government spends around 0.9% of GDP (Yende and Mthombeni, 2023), while other developing countries such as Brazil spend 1.1% of GDP and Chile spends 1.26% of GDP (DHET, 2018). In recent years the South African higher education sector has seen a decrease in government subsidies thus the burden on students has increased (De Jager & Baard, 2019). The portion of higher education institutions’ income coming from students rose from 24% in 2000 to 35% in 2015 (DHET, 2018). It is important to note that the student portion of money spent on higher education has some of it originating from government coffers, for example in 2015 about 40% of the fees paid by students were from NSFAS (DHET, 2018).\n\nNSFAS has been one of the main vehicles to directly fund individual students who lack the funds to attend University. NSFAS funding has seen a more than fivefold increase from R5.9 billion in 2014 to R34.7 billion in 2020 (BusinessTech, 2021). On 16, December 2017 President Jacob Zuma announced the introduction of tuition-free education at higher education level for some students. The announcement indicated that those in households with a combined income of less R350 000 would be funded by the government (Department of Higher Education and Training (DHET), 2018). The announcement indicated that NSFAS would now be granting bursaries rather than loans (Mavunga, 2019). This gave rise to the question; is South Africa ready for tuition-free higher education? This article sought to assess the feasibility of tuition-free higher education for all in South Africa given its level of GDP based on literature.\n\nPolicy initiatives and government actions under the Apartheid government resulted in 19 racially and ethnically composed education departments (Bunting, 2006). Under the National Party apartheid government, higher education institutions had to have clear designations of which race group they were serving (Beale, 1998). Universities designated for whites received the bulk of funding and were more resourced than universities for other racial groups (Beale, 1992; Bunting, 2006). The participation rates in higher education reflected the inequality of the apartheid policies with whites having a 70% participation rate while they had only 10% of the population, blacks it was 9% while they constituted 80% of the population, coloureds it was 13% and for Indians it was 40% (Sehoole & Adeyemo, 2016).\n\nThe post-Apartheid administrations of South Africa have worked to reverse the policies of the Apartheid State (Wangenge-Ouma, 2012). Several policies have been promulgated to this effect (Mzangwa, 2019). These policies have been designed to ensure equal access to higher education and to ensure the affordability of higher education for the formally marginalized and the poor (Akala, 2023). Among them are Education White Paper 3, the National Student Financial Aid Scheme Act, 1999 (Act No. 56 of 1999, and The National Plan for Higher Education (Akala, 2023; Sehoole & Adeyemo, 2016).\n\nEducation White Paper 3 was promulgated in 1997 with one of its main goals being the broadening of access and participation in higher education irrespective of race, gender, ability or age (Boughey & McKenna, 2021). The policy also sought to redress the effects of Apartheid policies and to eradicate discrimination (Dreyer et al., 2020). With increased participation of historically marginalised groups, the policy is viewed as having been successful to a certain extent (Akala, 2023). However, groups such as students with disabilities are still facing challenges in participating in higher education (McKinney & Swartz, 2022).\n\nThe NSFAS Act (Act No. 56 of 1999) provided for the creation of a loan and bursary scheme that catered for eligible students coming from low-income households (Ede et al., 2022; Pillay et al., 2021). The loan and bursary scheme loan as NSFAS has played a critical role in facilitating the participation of formerly marginalised groups and of those from low-income households (de Villiers, 2023). As of 2017, the loan scheme has been transformed into a bursary scheme to cater for students from households earning less than R350 000 (DHET, 2018).\n\nThe National Plan for Higher Education was promulgated in 2001 with the goal of providing an implantation framework for policies such as Education White Paper 3 (Akala, 2023). The policy sought to ensure that the right to education for all became a reality in South Africa (Mouton, Louw & Strydom, 2013).\n\nFunding was one of the most important mechanisms used by the Apartheid government to ensure to achievement of set policy goals (Wangenge-Ouma, 2012). The post-Apartheid government of South Africa has recognised that to reverse the negative effects of Apartheid policies there is a need to make use of funding as a tool.\n\n\nMethod\n\nThe study used a scoping review to review literature on tuition-free higher education. A scoping review “is a preliminary assessment of the available literature to identify the nature and extent of the evidence (usually including ongoing research)” (Tulandi & Suarthana, 2021). To ensure scoping reviews are rigourous, methodological and transparent, the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Reviews checklist was designed (Tricco et al., 2018). The guidelines provided by the (PRISMA) Extension for Scoping Reviews statement were used to guide the review. The protocol for the review was registered and the details are on the ‘Data availability’ Extended data section.\n\nThe inclusion criteria called for articles published in English, articles that focused specifically on tuition-free education, higher education and South Africa. Articles which focused on tuition-free education at other levels of education such as primary and secondary education were excluded from the study. The articles considered also included grey literature that discussed tuition-free higher education in South Africa. Studies using quantitative, qualitative and mixed method methodologies were included to give a broad view of the subject.\n\nArticles were sourced from Google Scholar and Scopus. The search sought articles between the years 2015 and November 2023. However, articles outside of these dates were used when found through the snowball method and when considered relevant. The snowball method was also used to locate articles not identified through the search parameters.\n\nThe researcher screened and selected the articles on her own. Each report was screened through reading the title, abstract and conclusion. The search for articles yielded 125 articles. After removing duplicates, 120 articles were left. After reading through the selected articles, 3 articles were identified from the references of the articles. These articles were added to the final list of articles used in the study. Three articles seemed to meet the inclusion criteria but were found to be focused on tuition-free education in primary and secondary education and thus were excluded.\n\nThe result of screening the articles was 15 articles published between the years 2008 to 2022. One article looking at free education in other countries was included. This was done when the article were viewed to provide insights that might be helpful in a South African context. Identified articles were downloaded from the databases. Analysis of the articles entailed first examining the abstract, keywords, and methodology used in the study. This was followed by reading the whole article, in some cases reading several times to gain a deep insight into the conclusions reached.\n\nThe inclusion and exclusion criteria called for studies undertaken in South Africa, focused on tuition-free higher education and undertaken in the English language. Figure 1 shows the selection procedure for the articles.\n\nData charting was undertaken by one researcher. The data charting consisted of identifying the year of publication, the methodology used in the studies and information on tuition-free higher education. Focusing on the issue of tuition-free higher education the content of the studies was analysed. The focus was on the arguments for and against tuition-free higher education and the reasons offered in the studies (Figure 1).\n\n\nResults\n\nOf the 15 articles used in the study, one (7%) was published between the years 2005 and 2010, two (13%) between 2010 and 2015, 11 (73%) between 2016 and 2020, one (7%) between 2020 and 2023. The majority of the articles being published between 2016 and 2020 might be due to it being the period where the debate of tuition free education was at its peak due to the #feesmustfall protests that began in 2015. All but one (7%) articles were published in South Africa, the one which focused on other countries was included as it offered insights deemed useful to the South African context. Of the articles used in the study, six (40%) were grey literature and nine (60%) were academic articles. Of the nine academic articles, eight were based on qualitative designs, while one used quantitative designs. Table 1 and Table 2 provide a summary of the characteristics of the articles used in the scoping review.\n\n\nDiscussion\n\nThis scoping review sought to assess the ability of the South African government to meet the resource demands of free education. Wangenge-Ouma and Cloete (2008) contend that free education is too costly for South Africa and that difficult trade-offs need to be made to fund it as the government has finite resources which are needed in many sectors of the economy. Those arguing against free higher education in South Africa point to the fact that most of the students eligible for higher education come from high-income families thus funding free higher education will be essentially a tax on the poor (Cloete, 2015; Wangenge-Ouma & Cloete, 2008).\n\nIn January 2016, the South African government established the Commission of Inquiry into Higher Education and Training (also known as the Heher Commission) to investigate the feasibility of making higher education and training free (DHET, 2018). The interim report realised by the Heher Commission in November 2016 recommended that the government fully fund students from households with less than R122 000 annual income and also provide funding for the ‘missing middle’ students from households exceeding the upper limit (R122 000) but in need of funding. The final report deemed tuition-free education to be not feasible for South Africa and suggested a funding model whereby students are funded through income-contingent loans rather than the NSFAS loan. The income-contingent loans would be offered by banks and students would pay them back upon being employed. The Heher Commission viewed the NSFAS loan system to be plagued by numerous problems and inefficiencies hindering its success. The Heher Commission proposed that TVET colleges be free and that they be improved upon so they could be first-choice institutions for some students (DHET, 2018).\n\nCloete (2015) argues that free education in a developing country of the ilk of South Africa is “financially, empirically and morally wrong” (p.11). The author calls for the conversation to turn from free higher education for all to affordable higher education for all. This would mean students from different income groups would have to pay different costs. The author feels that it is morally indefensible to require the poor who earn amounts below a certain threshold to pay for higher education. In the same vein, the author points to it being morally indefensible for the rich not to pay anything for higher education. The author warns that if the government does not address issues related to the missing middle, that is the group which does not qualify for NSFAS yet finds it difficult to get loans, protests in the form of the Arab Springs will arise or a more scary revolution in the form of the French Revolution might occur.\n\nLanga, Wangenge-Ouma, Jungblut and Cloete (2017) point to past attempts at instituting free education in some African countries, among them Kenya, Mozambique and Uganda. The tuition-free higher education regime in these countries resulted in increased inequalities between the rich and the poor (Cloete, 2015). This was due to children of the political and business elites getting access to free higher education at the expense of the deserving and academically gifted poor. In addition, the attempts in these African countries to implement free higher education proved very costly in the long run resulting in poor public higher education institutions. Langa, Wangenge-Ouma, Jungblut and Cloete (2017) argue that free education in a highly unequal society, such as South Africa, can result in higher education benefits only accruing to the already privileged who already have the “economic, social and cultural capital necessary to participate and succeed in higher education”.\n\nde Gayardon (2019) assessed free higher education systems around the world. The author argues that free higher education does not naturally lead to increased access and success in higher education. The author points out that tuition-free higher education systems around the world are diverse economically and geographically. In countries with free education, philosophical and historical traditions drive the adoption of the free higher education policy. In some countries, free higher education is viewed as a right while some view it as a way to promote equal opportunities. The author points out that in some countries that offer free higher education, adjustments have had to be made to systems to ensure financial stability. In some cases this includes having a dual track system where some get free higher education while others pay, in some cases there has been an increased reliance on private institutions which require fees while public institutions remain free.\n\nBadat (2011) argues that the likely consequence of free education for all is that public higher education institutions will lose much-needed resources leading to poor outcomes, which may necessitate a movement of the wealthy to private institutions or overseas. Need for access to real opportunities for success. The author posits the idea of graduate tax whereby beneficiaries of government funding pay a tax, the revenue which is used to fund other students. Badat (2011) makes a distinction between free education for all and free education for those in need, advocating for the latter as important for social and economic mobility.\n\nYende and Mthombeni (2023) analysed the effect of tuition-free higher education. Their study used qualitative content analysis to analyse documents linked to tuition-free higher education. They looked at the issue through the lens of supply and demand as explained in economic theory. The authors pointed out that the current 0.9% of GDP spent on higher education was deemed insufficient and the South African government needed to double this amount to cover tuition-free education. They also posited that the government needs to increase GDP by at least R2.88 trillion to sustainably implement tuition-free higher education. The authors noted that money for tuition-free education was sourced from tax resources and that currently South African taxpayers were overburdened. The authors point out that one of the consequences of tuition-free higher education for the poor has been a shift from the economic burden from students and parents to higher education institutions. With increased enrolment due to tuition-free education, institutions face the burden of managing dwindling resources with a larger group of students. Dwindling resources means difficult decisions have had to be made regarding reducing the sizes of faculty and reducing support services. This has the effect of adversely impacting the quality of education offered by institutions. The dynamics of the job market have also been impacted by tuition-free higher education with an influx of graduates who are saturating the job market in some fields, with the result being higher competition in some fields.\n\nSefoka (2018) posits that free higher education should be merit-based rather than free for all. This would ensure that the quality of higher education is not compromised and maintain academic excellence. The author argues that it is difficult for a developing nation such as South Africa to fund free education for all due to limited resources which are needed for a variety of critical needs. Hlaka and Sefoka (2022) point out that the South African government is not obligated by any legal instrument to offer free higher education for all. The authors further point to the lack of resources in South Africa as a significant obstacle to the delivery of free higher education.\n\nDe Jager and Baard (2019) found results which suggested free higher education in South Africa can lead to unsustainable demands on the fiscus. They point to South Africa lacking the key characteristics linked to countries that have been able to implement free higher education; these characteristics include a strong economy, a firm and wide tax base, low unemployment levels and limited access to higher education. The results of the study also point to the South African government needing to take care of more pressing demands such as those of basic education and health services thus reducing the portion of government resources that can be apportioned to free higher education. Other major issues highlighted in the study that hinder providing free education for all are corruption and wasteful expenditure by government departments. Dunga and Mncayi (2016) in a study conducted at a South African university found results suggesting that students did not believe the government should offer free education. The students felt it was not feasible while those who advocated for it felt it should be for the academically deserving only.\n\nMlambo, Hlongwa and Mubecua (2017) question the feasibility and sustainability of tuition-free education in South Africa. They point to the economic challenges faced by South Africa and the need to ensure that funds for free education are not supplanted by other departments. They offer several recommendations which can help the South African government maintain the current free higher education for low-income students regime. The first recommendation is that government should pursue private-public partnerships. With the private sector benefitting from graduates coming from Universities, it can participate in higher education through helping to fund students. The authors point to the need for new infrastructure in universities to accommodate the increase in students due to free education. The authors point to the need to increase funding in TVET colleges, TVET colleges provide vital education which is both practical and theoretical. The authors suggest that oversight over universities be increased to limit instances of wasteful expenditure and corruption.\n\nThe Public Service Association (2016) offered its perspective on South African higher education. The organisation pointed out that while the issue of fees had taken centre stage in debates about equity in higher education the focus should also be put on other structural matters. For instance, the organisation noted that one of the issues causing poor graduation rates in Universities was poor basic education thus there was a need for government to address the issue of basic education. The organisation felt free education for all would not be feasible given the competing demands on the government purse.\n\nUniversities South Africa (USAf) (2017) support a cost-sharing model between the state and the students, this is based on the idea that higher education is both a public good and a private good. The organisation points to a need for a mechanism designed for the poor and academically deserving but contends that tuition-free education is not feasible in South Africa. The main concerns of the organisation are the lack of clarity on how the government will fund free education in the long term and the apparent lack of capacity and competence shown in the past by the government through not honouring its commitment to avail subsidies to universities.\n\nMotala, Vally, and Maharajh (2018) argue that tuition-free higher education on its own is not adequate to solve the societal problems in South Africa. The authors suggest that students should receive funding for the full cost of study including food, books, accommodation, travel and registration fees. They suggest that funds for tuition-free education can be raised through taxation part of that taxation being increasing the tax paid by the top 10% of income earners in South Africa. The top 10% of earners in South Africa earn 60 to 65% of the income in South Africa, thus the authors argue this presents a large pool of tax revenue. The authors further suggest that there should be clear timelines set for plans to implement tuition-free higher education.\n\nFifteen articles were reviewed to assess their position on the feasibility of tuition-free education is feasible in South Africa. Several lessons were gathered from the articles. Authors on the subject of tuition-free higher education make a distinction between tuition-free higher education for all and tuition-free education for the poor and academically deserving (Cloete, 2015). This distinction is important in the context of South African higher education, as the latter seems to receive support from most stakeholders.\n\nA key consideration in the discussion of the feasibility of tuition-free higher education in South Africa is resource availability. The South African government operates within the confines of a limited budget (Wangenge-Ouma, 2008). Given the competing demands of the South African fiscus, there is an argument that the funding of tuition-free higher education results in the defunding or underfunding of other important government services such as healthcare and social security programs.\n\nThe calls for tuition-free higher education in South Africa are not novel calls on the African continent. Other countries tried tuition-free higher education policies post-independence. These policies were instated to reverse colonial inequalities and aggressively promote education (Langa et al., 2017). These well-meaning attempts at tuition-free higher education resulted in increased inequalities between the poor and, political and business elites. This is a cautionary tale for South Africa that the promotion of tuition-free higher education can have the unintended consequences of creating or furthering inequalities between elites and the poor. Another possible result of the migration of elites to foreign universities and private institutions was the result in the African countries that attempted to institute tuition-free higher education policies.\n\nIt is important to keep in mind that the quality of higher education offered by South African institutions needs to be maintained or improved upon. It is therefore for tuition-free higher education proponents to carefully consider the effect of the policy on the quality of higher education (Badat, 2011). In the event of access increasing while quality drops, this will possibly result in a brain drain with qualified and experienced lecturers and researchers leaving for better countries and will result in the rich choosing private institutions.\n\nCountries with free higher education systems have certain characteristics that South Africa seems to lack at the current moment. These characteristics include a strong economy, a firm and wide tax base, low unemployment levels and limited access to higher education (de Gayardon, 2019). These characteristics play a role in ensuring tuition-free higher education is sustainably funded in the long term. A strong economy ensures the government has adequate resources to meet its obligations. Low unemployment levels are essential to ensure the government has a wide tax base that provides revenue for tuition-free higher education. South Africa has high unemployment levels and a relatively small proportion of the population that pays taxes. When this is coupled with corruption and wasteful expenditure (De Jager and Baard,2019), the sustainability of tuition-free higher education in South Africa is not assured.\n\nThe government of South Africa should not forget to look at other structural issues that are essential for improving access and participation in higher education. One of the issues is the need for improving the basic education system which has been producing a significant portion of students that are ill-equipped to participate in higher education (The Public Service Association, 2016). The result is that even if some of the students are granted access a significant portion struggles to complete studies on time and others fail to complete their studies. It is important that in considering offering tuition-free higher education for all the government consider other issues that hinder student success. These include access to books, housing and transportation. A possible source of resources for the government to fund tuition-free higher education for all is through increasing taxes on the top 10% of income earners in South Africa who earn a combined 60 to 60% of income (Motala, Vally, and Maharajh, 2018). However, since the bulk of tax revenue already comes from this demography such a policy will simply serve to overburden an already-burdened taxpayer group\n\n\nConclusion\n\nThe scoping review was designed to assess the feasibility tuition-free education in South Africa. The study sought to assess the feasibility of free higher education in South Africa. Results from the scoping review indicate that free higher education for all is not deemed feasible in South Africa. There is a view that the government has finite resources and funding free higher education will mean other more deserving services are neglected (DHET, 2018). Funding free higher education for all is also viewed as a tax on the poor, as most students from middle and upper-income households get admitted for higher education studies (Cloete 2015, Wangenge-Ouma & Cloete, 2008).\n\nA moral argument is also offered, with the indication that in a highly unequal society such as South Africa offering free higher education to the rich is morally indefensible (Cloete, 2015). Thus the a need for a fee regime that looks at the ability of the household to pay. Learning from the history and experiences of developing countries can also help in understanding the feasibility of free higher education for all in South Africa. Langa, Wangenge-Ouma, Jungblut and Cloete (2017) point to the failure of several African countries to sustain tuition-free higher education for all, with the result being the entrenchment of inequalities as political and business elites reaped the benefits at the expense of the poor.\n\nThe current GDP levels in South Africa are insufficient to support higher education and the government needs to double the percentage of GDP earmarked for higher education (Yende and Mthombeni,2023). The current tuition-free education policy in South Africa is already leading to an increased burden on universities affecting the quality of teaching and support services. Structural issues need to be addressed for tuition-free education for all to be successful in South Africa, for instance, the government need to ensure the quality of basic education is improved (The Public Service Association, 2016). Poor basic education means the poor fail to meet admission requirements for higher education, thus the inequalities the government seek to address will persist. The South African government’s management of the NSFAS loan does not inspire confidence that it will be able to sustain tuition-free higher education in the long term. The concern is that poor management, corruption and wastage of resources will lead to failure of tuition-free higher education policy (USAf, 2017).\n\nIt seems there is a consensus that free higher education for all is not feasible in South Africa. There is an understanding that free higher education for all and free education for the poor mean two different things. Thus some support free education for the poor as a moral imperative, given the high level of inequality in South Africa. In contrast to the majority of articles reviewed Motala et al. (2018) indicated support for free higher education and believe it is feasible if the government increase tax revenue through increasing tax revenues on the top 10% earners. However, there are concerns that increasing taxes will put a further burden on already overburdened taxpayers.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nName of repository- Zenodo\n\n• Title- Exploring the Potential of tuition-free HE PRISMA-ScR-Fillable-Checklist 2024.docx\n\n• DOI- 10.5281/zenodo.11120736.\n\n• Full reference- Ramasu, T. K., & Kanakana - Katumba, M. G. (2024). Exploring the Potential of tuition-free HE PRISMA-ScR-Fillable-Checklist 2024.docx. Zenodo. https://doi.org/10.5281/zenodo.11120737.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAbel JR, Dey I, Gabe TM: Productivity and the density of human capital. Journal of Regional Science. 2012; 52(4): 562–586. Publisher Full Text\n\nAkala B: Policy initiative on the right to higher education: South Africa (Tracing good and emerging practices on the right to higher education around the world). UNESCO IESALC; 2023. 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Publisher Full Text\n\nWangenge-Ouma G, Cloete N: Financing higher education in South Africa: Public funding, non-government revenue and tuition fees. South African Journal of Higher Education. 2008; 22(4): 906–919.\n\nWangenge-Ouma G: Tuition fees and the challenge of making higher education a popular commodity in South Africa. Higher Education. 2012; 64:831–844. Publisher Full Text\n\nWilliams G: Higher Education: Public Good or Private Commodity? London Review of Education. 2016; 14(1): 131–142. Publisher Full Text\n\nWorld Bank: Data|South Africa.2022a. Reference Source\n\nWorld Bank: Data|Denmark.2022b. Reference Source\n\nWorld Bank: GDP per capita (current US$) - European Union|.2023. Reference Source\n\nYende SJ, Mthombeni ZM: The Cost of Equality: Analyzing the Unforeseen Financial Strains of Fee-Free Higher Education in South Africa. E-Journal of Humanities, Arts and Social Sciences (EHASS). 2023; 4(11): 1380–1390. Publisher Full Text"
}
|
[
{
"id": "291745",
"date": "17 Jul 2024",
"name": "Zayd Waghid",
"expertise": [
"Reviewer Expertise Social justice education"
],
"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 very important study and one that has, since the implementation of the South African government's policy around \"free higher education\", warranted rigorous empirical research.\n\nHowever, the article has several shortcomings. In this regard, the article is not suitable at this point for being indexed and would require major revisions.\nFirstly, there is the absence of a research question to assist with the direction and focus of the study. Although, the authors have included the aim of the study, which is generally much broader than a research question, particularly since aims outline the objectives or goals of one's research, a research question is needed from the onset.\nSecond, the results section is very poor. There needs to be a detailed description of the findings in relation to an RQ. It would also have made sense to have themes related to each finding and then to build on these in the discussion section.\nThird, the first section of the discussion section is rather poor in that it appears to be written like a literature review. One would have expected deeper discussions pertaining to the findings, particularly regarding its implications for policy and practice.\nFourth, the conclusion section needs to underscore the study's limitations and offer recommendations for further inquiry.\n\nOther comments:\nAs far as I know, Egypt and Saudi Arabia are still considered developing nations. Please check your reference.\n\nThe article would benefit from being language edited to ensure that it enhances the overall flow of ideas and arguments throughout 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? Yes\n\nIs the statistical analysis and its interpretation appropriate? No\n\nAre the conclusions drawn adequately supported by the results presented in the review? No\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/13-526
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https://f1000research.com/articles/13-669/v1
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21 Jun 24
|
{
"type": "Case Report",
"title": "Case Report: Acute large bowel obstruction with actinomycosis of the sigmoid colon mimicking neoplasm",
"authors": [
"Mohamed Hajri",
"Rami Zouari",
"Ines Mallek",
"Dhouha Bacha",
"Rached Bayar",
"Sana ben slama",
"Rami Zouari",
"Ines Mallek",
"Dhouha Bacha",
"Rached Bayar",
"Sana ben slama"
],
"abstract": "Introduction Actinomycosis is an uncommon inflammatory bacterial disease caused by Actinomyces species, especially Actinomyces Israeli. Abdominopelvic forms are relatively rare and may involve the colon as a solid mass, mimicking a malignant tumor.\n\nCase presentation A 68-year-old Tunisian man, with a history of diabetes, hypertension, penicillin allergy, and renal failure, presented to the emergency department with abdominal pain, vomiting, and bowel obstruction. CT scan showed an acute intestinal obstruction upstream with obstructive tissular mass at the sigmoid colon. Emergency surgery revealed a sigmoid mass and a pre-perforative cecum. Subtotal colectomy was performed, with ileostomy and distal end closure. Histological examination confirmed Actinomyces infection. The patient was then placed on long-term doxycycline and Bactrim, with no recurrence over a 9-month follow-up period.\n\nConclusion Abdominal actinomycosis, though rare, presents diagnostic challenges. It can be mistaken for malignancy, leading to unnecessary surgery in non-complicated cases, since it is effectively treated by antibiotics. In complicated cases, a combined approach involving both surgery and antibiotic therapy is necessary until the infection is completely eradicated.",
"keywords": [
"Abdominal actinomycosis",
"actinomyces",
"acute intestinal obstruction",
"antibiotic therapy",
"surgery."
],
"content": "Introduction\n\nActinomycosis is an uncommon inflammatory bacterial disease caused by Actinomyces Israeli, a Gram-positive anaerobic bacterium typically found in the digestive and genital tracts. This condition is often mistaken for a tumor or presents as an inflammatory mass. It can also lead to the formation of abscesses.1 The progression is slow and insidious, with local inflammation extending across different organs without confinement to a single one.2 Actinomyces typically colonizes the oral cavity, bronchi, gastrointestinal and female genital tracts. In the gut, it preferentially involves the stagnated zones, notably the caecum, the appendix, and the sigmoid colon. Clinical manifestations and radiological findings are nonspecific.3 Since acute and complicated forms require early treatment, most forms are diagnosed postoperatively. In this case report, we present a rare occurrence of colonic actinomycosis mimicking neoplasm and causing acute large bowel obstruction.\n\n\nCase presentation\n\nA 68-year-old Tunisian man, with a history of diabetes, hypertension, penicillin allergy, and renal failure, with no prior surgical history, presented to the emergency department with abdominal pain, vomiting, and bowel obstruction. The patient reported a similar symptomatology over the last two months, which resolved spontaneously. He also complained of chronic abdominal discomfort. On examination, he was hemodynamically stable. There was no fever. The abdominal examination revealed a distended and resonant abdomen, tender throughout, with a palpable mass in the left iliac fossa. The laboratory tests were normal, except for a previously known renal failure. We followed up with an abdominal CT scan without contrast, which revealed an acute intestinal obstruction upstream of a suspected obstructive tissue process at the sigmoid colon, with associated satellite lymph nodes and a dilated cecum measuring 12 cm (Figure 1). Emergency surgery was decided after a brief resuscitation. Exploration of the abdomen by midline laparotomy revealed a mass in the sigmoid loop, measuring 7 cm along its major axis, adherent to the omentum, the parietal peritoneum, and the posterior wall, with dilation of the entire upstream colonic frame. The cecum was dilated to 13 cm with a weakened, pre-perforative wall. We underwent a total colectomy with ileostomy and distal end closure (Figure 2). The postoperative recovery was uneventful. Gross pathologic examination of the surgical specimen revealed a stenosing lesion of the sigmoid colon with ulcerated surface mucosa. Histological examination showed acute inflammatory reaction and abscess formations surrounding clumps of short branching basophilic filaments stained with PAS (Periodic Acid Schiff). Dense fibrosis was associated. There was no granulomatous inflammation (Figures 3, 4). Actinomyces infection was confirmed. The patient was then placed on long-term doxycycline and Bactrim. Upon follow-up, he was seen regularly for 9 months. No recurrence has been diagnosed. The restoration of bowel continuity was postponed until completing a full year of antibiotic therapy.\n\n\nDiscussion\n\nActinomycosis is a rare granulomatous inflammation caused by Actinomyces species, especially Actinomyces Israeli, gram-positive anaerobic bacteria that are part of the normal human flora, colonizing the oral, digestive, and urogenital tracts.4,5\n\nActinomyces species have low virulence potential and require mucosal barrier disruption. This can occur after surgery, trauma, or in the presence of a foreign body, or in immunosuppression situations.6\n\nAll tissues may be infected, and we can distinguish four types of pre-ponderant infections, cervicofacial 50 to 60%, thoracic 15%, abdominopelvic 20%, and rarely disseminated disease.7\n\nActinomycosis commonly occurs between the ages of 20 and 60 years old and affects men three times more than women.8 Nevertheless, its incidence in women is increasing, associated with the rising use of intrauterine devices, reaching 75% of patients with pelvic actinomycosis in some studies.8\n\nAbdominopelvic forms can mimic malignant tumors due to their chronic evolution. They have no specific clinical presentation and patients can consult for various symptoms such as chronic abdominal pain, abdominal mass, nausea, vomiting, anorexia, weight loss, and bleeding.9\n\nThis explains that it can evolve insidiously and manifest as a voluminous mass at the time of diagnosis.\n\nOur case described an unusual presentation of abdominopelvic actinomycosis characterized by large bowel obstruction occurring in a 75-year-old patient with none of the risk factors cited above. It was due to a pseudotumoral sigmoid mass with a pre-perforative cecum.\n\nDifferential diagnoses in patients presenting with abdominal forms include appendicitis, diverticulitis, inflammatory bowel disease, tuberculosis, and bowel malignancies.10\n\nBeing a chronic suppuration, abdominal actinomycosis leads to the formation of multiple adjacent abscesses and to a large inflammatory reaction that can potentially invade neighboring tissues, appearing as a locally advanced tumor.6,10\n\nIn addition, being able to spread through hematogenous ways, actinomycosis may cause distant infections, mimicking distant metastasis.10\n\nThe management of abdominopelvic actinomycosis depends on its presentation.\n\nThe diagnosis can be suspected on CT scan findings, and confirmed after undergoing CT-guided puncture where Actinomyces species can be identified.\n\nIn such cases, the patient will undergo long-term antibiotherapy, such as parenteral penicillin G, followed by oral penicillin V or amoxicillin for up to 12 months. Alternative antibiotics like Tetracycline, Erythromycin or Clindamycin can be given in patients with penicillin allergy.\n\nGenerally, the prognosis is favorable and treatment efficacy is verified through ultrasonography or computer tomography.8,11,12\n\nHowever, in most cases, actinomycosis is only diagnosed postoperatively. Indeed, confusion with a malignant mass, or manifestation in complicated forms, as in our observation, often leads to primary surgery.\n\nAccording to the literature, actinomycosis involving the colon and presenting as acute abdomen or acute large bowel obstruction is rarely reported.\n\nA review of the literature was conducted using the PubMed Database. We used “actinomycosis”, “colon”, “intestinal obstruction”, and “acute abdomen” as keywords. We excluded articles that reported extrinsic invasion of the colon, non-complicated colonic actinomycosis treated with antibiotics, and manuscripts not written in English.\n\nA total of 15 articles were found between 1980 and 2024.\n\nThe most commonly affected colonic segments were the ascending colon and the transverse colon. In almost all reported cases, emergency surgery was performed and the diagnosis was made postoperatively. All patients received prolonged antibiotic therapy after surgery, with no reported recurrence.\n\nIn only one case, as detailed by Lin et al.,13 the diagnosis was made through endoscopic biopsy conducted during an episode of acute infectious colitis, suspected to be caused by actinomycosis infection. The patient was successfully treated with antibiotics and did not require surgery.\n\nThe details are summarized in Table 1.\n\nIn our particular case, emergency surgery was inevitable given the obstructive character of the sigmoid colon lesion. We underwent a total colectomy due to the pre-perforative lesions appearing on the cecum. Due to anatomopathological findings, he was prescribed long-term antibiotherapy based on doxycycline and Bactrim regarding his penicillin allergy.\n\nDespite appropriate treatment, abdominal actinomycosis may recur and patients should be followed up. Currently, there is no standardized protocol for this monitoring. However, patients should at least undergo ultrasonography or computed tomography after treatment.12\n\n\nConclusion\n\nAbdominal actinomycosis, though rare, presents diagnostic challenges. It can be mistaken for malignancy, leading to unnecessary surgery in non-complicated cases. The diagnosis should be considered when there is an abdominal mass with local invasion signs, whether or not an infectious syndrome is present. As a result, all efforts should be made to confirm the diagnosis. Once the diagnosis is certain through microbiological or pathological examinations, antibiotic treatment with penicillin should be started, lasting for six to 12 months, depending on the extent of the infection. This extended treatment duration helps reduce the risk of recurrence and often completely resolves the lesions. In complicated cases, a combined approach involving surgery and antibiotic therapy is necessary until the infection is completely eradicated.\n\nWritten informed consent was obtained from the patient for the publication of this case report and the accompanying images.",
"appendix": "Data availabilty statement\n\nNo data are associated with this article.\n\n\nReferences\n\nValour F, Sénéchal A, Dupieux C, et al.: Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect. Drug Resist. 2014 Jul 5; 7: 183–197.\n\nCaplan E, Deputy M, Arul D, et al.: Actinomycosis of the omentum with invasion of the abdominal wall, small bowel and transverse colon mimicking malignancy. BMJ Case Rep. 2019 Jan 28; 12(1): bcr-2018-227728.\n\nBoyanova L, Kolarov R, Mateva L, et al.: Actinomycosis: a frequently forgotten disease. Future Microbiol. 2015 [cited 2024 Feb 8]; 10(4): 613–628.Publisher Full Text\n\nTârcoveanu E, Vasilescu A, Andronic D, et al.: Abdominal Actinomycosis Mimicking Colon Cancer. Chir. Buchar. Rom. 2019; 114(2): 251–258.\n\nHajri M, Omrani S, Ferjaoui W, et al.: Actinomycosis mimicking a pancreatic head neoplasm: A case report. Int. J. Surg. Case Rep. 2022 Feb 1; 91: 106794.\n\nPamathy G, Jayarajah U, Gamlaksha DS, et al.: Abdominal actinomycosis mimicking a transverse colon malignancy: a case report and review of the literature. J. Med. Case Rep. 2021 May 3; 15(1): 224.\n\nValko P, Busolini E, Donati N, et al.: Severe large bowel obstruction secondary to infection with Actinomyces israelii. Scand. J. Infect. Dis. 2006; 38(3): 231–234.\n\nKetata S, Ben Mabrouk M, Derbel F, et al.: Tumoral form of abdominal actinomycosis: a retrospective case series of seven patients. Rev. Med. Interne. 2010 Nov; 31(11): 735–741.\n\nZamani F, Sohrabi M: Clinical, endoscopic, and histopathological aspects of sigmoid actinomycosis; a case report and literature review. Middle East J. Dig. Dis. 2015 Jan; 7(1): 41–44.\n\nYang SS, Im YC: Severe abdominopelvic actinomycosis with colon perforation and hepatic involvement mimicking advanced sigmoid colon cancer with hepatic metastasis: a case study. BMC Surg. 2018 Aug 2; 18(1): 51.\n\nVasilescu AM, Târcoveanu E, Lupascu C, et al.: Abdominopelvic Actinomycosis-The Diagnostic and Therapeutic Challenge of the Most Misdiagnosed Disease. Life Basel Switz. 2022 Mar 17; 12(3): 447.\n\nManterola C, Grande L, Riffo-Campos ÁL, et al.: Clinical aspects of abdominal actinomycosis: a systematic review. ANZ J. Surg. 2020 Jul; 90(7–8): 1465–1468.\n\nLin C, Hsu CW, Tseng JH, et al.: Colonic Actinomycosis Presenting as Diffuse Colitis and Protein-Losing Enteropathy: A Case Report. Gastrointest. Endosc. 2003 Sep 1; 58(3): 448–451.\n\nLyew MA, Morris C, Smith K, et al.: Case report: Colonic actinomycosis–A rare cause of a locally advanced colonic tumour. Int. J. Surg. Case Rep. 2023; 105: 107957.\n\nMorais-Kansaon MJ, Antonacci-Condessa V, Andrade-Ribeiro RM, et al.: Colonic pseudotumor caused by abdominal actinomycosis: A case report. Cir. Cir. 2020; 88(S1): 102–105.\n\nJabi R, Ramdani H, Elmir S, et al.: Pseudotumoral Actinomycosis Mimicking Malignant Colic Disease: A Case Report and Literature Review. Visc. Med. 2019 Oct 14; 36(4): 333–337.\n\nHui K, Chan B, Yuen K: Colonic actinomycosis: a pseudo-tumour that mimics colonic neoplasm. Hong Kong Med. J. 2019; 25(4): 334–336.\n\nGarcía-Zúñiga B, Jiménez-Pastrana MT: Acute abdomen with actinomycosis of the colon: a case report. Cir. Cir. Engl. Ed. 2016; 84(3): 240–244.\n\nValko P, Busolini E, Donati N, et al.: Severe large bowel obstruction secondary to infection with Actinomyces israelii. Scand. J. Infect. Dis. 2006 Jan 1; 38(3): 231–234.\n\nSaha S, Mukherjee AJ, Agarwal N, et al.: Colonic actinomycosis masquerading as perforated colonic carcinoma. Trop. Gastroenterol. 2007 Apr 1; 28(2): 74–75.\n\nJung EY, Choi SN, Park DJ, et al.: Abdominal actinomycosis associated with a sigmoid colon perforation in a patient with a ventriculoperitoneal shunt. Yonsei Med. J. 2006; 47(4): 583–586.\n\nFilippou D, Psimitis I, Zizi D, et al.: A rare case of ascending colon actinomycosis mimicking cancer. BMC Gastroenterol. 2005; 5: 1–5.\n\nIşık B, Aydın E, Söğütlü G, et al.: Abdominal actinomycosis simulating malignancy of the right colon.2005 [cited 2024 Feb 18]. Reference Source\n\nBittencourt JAF, Andreis EL, Lima EL, et al.: Actinomycosis simulating malignant large bowel obstruction. Braz. J. Infect. Dis. 2004; 8: 186–189.\n\nFerrari TC, Couto CA, Murta-Oliveira C, et al.: Actinomycosis of the Colon: A Rare Form of Presentation. Scand. J. Gastroenterol. 2000 Jan 1; 35(1): 108–109."
}
|
[
{
"id": "299051",
"date": "22 Jul 2024",
"name": "Mhasisielie Zumu",
"expertise": [
"Reviewer Expertise Gastric actinomycosis"
],
"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) Details on blood sugar controlled, alcohol used, smoking, oral hygiene and history of prolonged used of PPI may be mentioned, if present.\n\n2) Serum HbA1c level at admission may be mentioned 3) No risk factor of immunosuppression? - diabetes mellitus is present. 4) Is the Actinomyces infection only in sigmoid colon or in caecum as well causing weakened, pre-perforative wall ?- what was the histopathology report ? 5) \"We underwent a total colectomy with ileostomy and distal end closure\" - grammar check\n\n6) The surgery done has been stated as subtotal colectomy in the abstract. However, subsequently it has been mentioned as total colectomy. please correct it 7) Was sulphur granules looked for /found in histopathology? 8) pre-preforative wall- terminology to be check\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": [
{
"c_id": "12229",
"date": "29 Aug 2024",
"name": "Mohamed Hajri",
"role": "Author Response",
"response": "I am grateful for the time and effort you and the reviewers have invested in offering valuable feedback on my manuscript. I sincerely appreciate the reviewers' insightful comments on our paper. I have made revisions to incorporate most of the suggestions provided by the reviewers. Regarding comment number 7, the germ was only found on one slide HE, so PAS staining was done and showed aspects of actinomycosis with “spherical elements” most certainly sulfur granules. But as they were few in number and paraffin block almost insufficient we designated them only by “spherical cluster” (in Figure 3). And for comment number 8, we have checked the term \"pre-perforative\", which has been used in several scientific documents and articles. However, we remain open to any alternative terminology that may be proposed. Thank you, sincerely."
}
]
},
{
"id": "311560",
"date": "21 Aug 2024",
"name": "Prajwal Dahal",
"expertise": [
"Reviewer Expertise 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\nI would like to congratulate the author for writing a comprehensive case report in a entity that is less encountered in clinical practice. The manuscript adds on our current knowledge of actinomycosis infection of bowel and stimulates clinicians and radiologists to consider it as a differential of bowel mass. I suggest minor revision for betterment.\n1) Please provide values of vitals, blood parameters and serum urea/ creatnine at presentation\n2) In a case report, it is advised to limit number of reference to below 10. Kindly consider that.\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": "12332",
"date": "30 Aug 2024",
"name": "Mohamed Hajri",
"role": "Author Response",
"response": "Thank you very much for your positive feedback and constructive suggestions. I appreciate your time and effort in reviewing my manuscript. I will include the values of vitals, blood parameters, and serum urea/creatinine at the time of presentation in the revised version. I understand the recommendation to limit the number of references to below 10. However, many of the references have been used in the summary table to cite the different cases from the literature. Would it be feasible to keep them included? If you still recommend reducing the number of references, I would be willing to do so. Thank you again for your valuable input."
}
]
}
] | 1
|
https://f1000research.com/articles/13-669
|
https://f1000research.com/articles/13-976/v1
|
28 Aug 24
|
{
"type": "Systematic Review",
"title": "The Association between Early-Onset Pancreatic Ductal Adenocarcinoma and Patients Survival: A Systematic Review and Meta-Analysis",
"authors": [
"Kaka Renaldi",
"Andy William",
"Andy William"
],
"abstract": "Background In recent years, the incidence of early-onset pancreatic cancer (EOPC) has increased. Several studies comparing the survival of patients with EOPC to those with average-onset pancreatic cancer (AOPC) have reported mixed results. We aimed, therefore, to perform a meta-analysis summarizing the current evidence.\n\nMethods We searched the MEDLINE and EMBASE databases for relevant articles published through March 2024. Articles comparing the survival of patients with EOPC – defined as pancreatic ductal adenocarcinoma (PDAC) diagnosed at ≤ 50 years of age – and AOPC were included in the present meta-analysis. The primary outcome was the pooled adjusted hazard ratio (aHR), and the risk of bias analysis was performed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using a random-effects model.\n\nResults A total of 17 studies were eligible for the primary analysis, the results of which indicated that patients with EOPC had a longer overall survival than those with AOPC (aHR = 0.80; 95% confidence interval [CI], 0.74–0.86; P < 0.001). The rate of distant metastasis was higher in EOPC than AOPC; however, patients with EOPC also received more treatments than those with AOPC.\n\nConclusions Patients with EOPC had a better prognosis than those with AOPC. Clinicians must ensure that patients with PDAC receive early and appropriate treatment to improve their survival.",
"keywords": [
"Meta-analysis",
"Pancreatic neoplasms",
"Survival",
"Young adult"
],
"content": "Introduction\n\nAs of 2022, pancreatic cancer is the 12th most common type of cancer and the 6th largest contributor of cancer-related mortality worldwide, with a relative 5-year survival rate of 12.5%.1 According to the Surveillance, Epidemiology, and End Results (SEER) database, the median age of patients diagnosed with pancreatic cancer is 70 years old2; however, the number of younger patients diagnosed with pancreatic cancer, termed early-onset pancreatic cancer (EOPC), is increasing.3\n\nThere is no consensus regarding the definition of EOPC as it pertains to age; however, it is largely used to describe patients who are ≤ 50 years of age when diagnosed with pancreatic cancer.4–7 Additionally, pancreatic cancer that is diagnosed at age < 45 years old is occasionally defined as very early-onset pancreatic cancer (VEOPC).8 EOPC accounts for 0.87–11.50% of pancreatic cancers, depending on the study population.9,10 Although EOPC occurs more often in males, the age-adjusted incidence rate increased significantly more in young females than their male counterparts.11 Several risk factors have been associated with EOPC, including heavy alcohol consumption, smoking, family history of pancreatic cancer, diabetes mellitus, obesity, and pancreatitis.12 Some studies also showed unique molecular profiles in patients with EOPC, such as a higher frequency of wild-type KRAS and higher mutation rates of CDKN2A, SMAD4, and FOXC2.13 Although the effects of these genomic alterations on tumor behavior are still unclear, some studies have shown that patients with EOPC often present with higher rates of distant metastasis.14\n\nStudies investigating differences in survival times between patients with early-onset PDAC and those with average-onset PDAC (AOPC) have shown conflicting results. Several studies have shown that patients with EOPC have a better prognosis than those with AOPC4,15; however, some studies have shown that patients with EOPC have a worse survival than those with AOPC.9,14 Additionally, some studies did not find any significant difference in survival between patients with EOPC and those with AOPC.5,7 To the best of the authors’ knowledge, however, a meta-analysis on this topic has not yet been performed. In the present study, therefore, we conducted a meta-analysis of studies that compared the survival rates of patients with EOPC to those with AOPC, specifically focusing on pancreatic ductal adenocarcinoma (PDAC), which is the most common type of pancreatic cancer (approximately 90%).16\n\n\nMethods\n\nThe present systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist.17\n\nWe used the PICOTS framework18 to define the review questions, as follows: Population = patients with PDAC; Index Prognostic Factor = EOPC; Comparator Prognostic Factor = adjusted for cancer stage/resectability status/tumor size; Outcome = Survival; Timing = age at diagnosis; Setting = all care settings. Based on the review question, the inclusion criteria were as follows: 1) studies that compared the overall survival between patients with EOPC and those with AOPC, although to maximize the number of studies included, if only cancer-specific survival were available, studies were still accepted; 2) studies that defined EOPC as patients who were diagnosed with PDAC at ≤ 50 years of age (although various definitions of EOPC are used in the relevant literature, we chose this cut-off because it was the most frequently used definition in the literature4–7,9,14,19–24; by this definition, studies that used a cut-off of 45 or 40 years of age were also included, and the comparator group in each study was categorized as the AOPC group); and 3) survival analysis must be adjusted to the tumor stage (either by regression analysis or matching) – if the American Joint Committee on Cancer (AJCC) cancer stage25 was unavailable, we also accepted survival analysis, which was adjusted for tumor resectability or tumor size to maximize the number of studies included. The exclusion criteria were as follows: 1) studies with only abstracts available; 2) studies that did not present a hazard ratio and were inestimable from other values by the methods described by Tierney et al.26 and Hebert et al.27; and 3) studies that were not available in English.\n\nTwo independent reviewers searched the MEDLINE and EMBASE databases for articles published through March 2024. For MEDLINE, the following search terms were used: (early-onset pancreatic cancer [Title/Abstract]) OR ((young [Title/Abstract] AND pancreatic cancer [Title/Abstract])). For EMBASE, the following terms were used: ‘early-onset pancreatic cancer’:ab,ti OR (young:ab,ti AND ‘pancreatic cancer’:ab,ti). We also reviewed the reference lists of related papers to identify additional studies.\n\nTwo independent reviewers extracted the data from included studies using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prognostic Factor Studies (CHARMS-PF).18 The following data were extracted: authors; year of study; study design; definition of EOPC and AOPC; number of subjects; period of recruitment; evaluation of survival; median follow-up; adjustment to other variables; hazard ratio; rate of distant metastasis; and proportion of subjects who received surgery, chemotherapy, or radiotherapy. Additionally, the risk of bias for each study was analyzed using the Quality in Prognostic Factor Studies (QUIPS) tool,28 which evaluates the following aspects: adequate study participation; study attrition; prognostic factor measurement; outcome measurement; adjustment for other prognostic factors; and statistical analysis and reporting. Permission has been obtained from the creator to use the QUIPS tool.\n\nThe Review Manager (RevMan) 5.3 program (The Nordic Cochrane Center, Copenhagen, Denmark)29 and R 4.3.2 program (R Core Team, Vienna, Austria)30 were used to perform the meta-analysis. The primary outcome was overall survival. The adjusted hazard ratio (aHR) for each study was used in the pooled analysis and presented as forest plots. If there was a study in which survival analysis was stratified based on cancer stage or resectability, multiple hazard ratios were first pooled into one value. If the aHR was not stated, it was estimated using the methods described by Tierney et al.26 and Hebert et al.27 If there was substantial heterogeneity between the studies, we used a random effects analysis to calculate the pooled aHR, otherwise, a fixed-effects analysis was used. Additionally, we performed a pooled hazard ratio analysis for cancer-specific survival (CSS), disease-free survival (DFS), progression-free survival (PFS), and recurrence-free survival (RFS).\n\nWe also performed sensitivity analyses, based on the type of survival analysis, age cutoff, presence of matching, regression analysis, published hazard ratio only, and adjustment for several covariates, as well as a subgroup analysis of the patients who underwent surgery. Publication bias was assessed using funnel plots, and Egger’s test was performed using ProMeta 3 (Internovi, Cesena, Italy).31 Additionally, we calculated the pooled risk ratios for the rates of distant metastasis (stage IV cancer) and treatment (surgery, chemotherapy, and radiotherapy).\n\n\nResults\n\nThe PRISMA study flow diagram is shown in Figure 1. A total of 522 records were initially obtained from MEDLINE, EMBASE, and the reference lists of the eligible studies, after the removal of duplicates, of which 46 were assessed for eligibility. Articles that only included patients with EOPC or used different age cutoffs for EOPC (e.g., age < 55, < 60, or < 70 years) were excluded. Table S1 shows a list of the excluded studies and the reasons for their exclusion. In total, 17 studies were included in the final analysis.\n\nTable 1 shows the characteristics of the 17 studies included in the present meta-analysis. The total number of patients with EOPC was 33,274 subjects, while that of those with AOPC was 563,198.\n\n\n\n- 34 (total, before PSM)\n\n- 34 (after PSM)\n\n\n\n- 665 (total, before PSM)\n\n- 68 (after PSM)\n\n\n\n- Median OS: 17 months vs. 32 months; P = 0.970\n\n- 5-year OS: 5.4% vs. 18.0%\n\n\n\n- 3172 (after PSM)\n\n\n\n- 3172 (after PSM)\n\n\n\n- Median survival: Not stated\n\n- 5-year OS: 6.1% vs 8.6%, p = 0.003\n\n- 5-year CSS: 6.7% vs 9.7%, p < 0.001\n\n\n\n- Median survival: Not stated\n\n- 1-year OS for stage 0-2 disease: 72.4% (95%CI: 71.2%–73.7%) vs. 53.3% (95%CI: 52.9%–53.7%)\n\n- 1-year OS for stage 3 disease: 47.6 (95%CI: 45.1%–50.0%) vs 37.8% (95%CI: 37.1%–38.4%)\n\n- 1-year OS for stage 4 disease: 24.8% (95%CI: 23.8%–25.8%) vs 14.8% (95%CI: 14.5%–14.9%)\n\n\n\n- aHR age < 45 y.o. vs. 45–59 y.o. = 0.93 (95% CI 0.88–0.98; P = 0.010)\n\n- aHR age < 45 y.o. vs. 60–69 y.o. = 0.91 (95% CI 0.85–0.96; P = < 0.001)\n\n- aHR age < 45 y.o. vs. 70–79 y.o. = 0.86 (95% CI 0.81–0.92; P = < 0.001)\n\n- aHR age < 45 y.o. vs. >79 y.o. = 0.85 (95% CI 0.81–0.91; P = < 0.001)\n\n\n\n- Median OS = 11 months vs. 9 months; P = 0.28\n\n\n\n- Median OS: 5.67 months vs. 8.00 months; P = 0.12\n\n- 5-year OS: 3.3% vs. 0%\n\n\n\n- Median OS: 19 months vs. 16 months; P = 0.007\n\n- 5-year OS = 24% vs. 11%; P = 0.005\n\n- 10-year OS = 17% vs. 3%, P < 0.001\n\n\n\n- Median OS: 9.2 months vs. 6.0 months; P < 0.001\n\n\n\n- - Median OS: 9.36 months vs. 8.04 months; P = 0.403\n\n\n\n- Median OS: 5.9 months vs. 4.5 months; P < 0.001\n\n- 1-year OS: 28.4% vs. 22.6%; P < 0.001\n\n- 2-year OS: 15.3% vs. 10.1%; P < 0.001\n\n- 3-year OS: 11.4% vs. 6.6%; P < 0.001\n\n- 5-year OS: 8.2% vs. 4.0%; P < 0.001\n\n\n\n- Median OS: 18.7 months vs. 17.6 months; P = 0.75\n\n\n\n- Median OS: 30.6 months vs. 31.0 months\n\n- 1-year OS: 73.3% vs. 79.5%\n\n- 3-year OS: 43.9% vs. 43.9%\n\n- 5-year OS: 33.0% vs. 31.0%\n\n\n\n- Median OS: 16.9 months vs. 17.1 months; P = 0.565\n\n\n\n- Median OS: 9 months vs. 8 months; P = 0.002\n\n- 1-year OS: 38.4% vs. 36.8%\n\n- 3-year OS: 11.1% vs. 10.1%\n\n- 5-year OS: 6.9% vs. 5.8%\n\n\n\n- Median OS: 7.0 months vs. 6.0 months; P < 0.001\n\n\n\n- aHR age 20–40 vs. 40–60 = 0.54 (95% CI 0.50–0.58; P < 0.001)\n\n- aHR age 20–40 vs. 60–80 = 0.45 (95% CI 0.42–0.49; P < 0.001)\n\n- aHR age 20–40 vs. >80 = 0.30 (95% CI 0.28–0.33; P < 0.001)\n\n\n\n- Median CSS age 20–40 vs. age 40–60 vs. age 60–80 vs. age >80 = 36.0 months vs. 10.0 months vs. 8.0 months vs. 4.0 months\n\n- 5-year CSS age 20–40 vs. age 40–60 vs. age 60–80 vs. age >80: 44.7% vs. 16.9% vs. 13.8% vs. 8.7%\n\n\n\n- aHR locally advanced = 0.47 (95% Cl 0.32–0.69; P = 0.005)\n\n- aHR metastatic = 0.66 (95% Cl 0.48–0.89; P =0.025)\n\n\n\n- Median OS: 23.4 months vs 10.3 months\n\n- P < 0.001\n\nTable 2 shows the risk of bias for the 17 studies included in the present meta-analysis.\n\nOverall survival (OS)\n\nFigure 2 shows the forest plot of the OS analysis of the studies included in the present meta-analysis. The patients with EOPC had a better OS than those with AOPC (aHR = 0.80; 95% confidence interval [CI], 0.74–0.86; P < 0.001). The range of median survival for EOPC subjects was 5.7─36.0 months, while the range of median survival for AOPC patients was 4.0─32.0 months.\n\nThe sensitivity analysis is shown in Table 3.\n\nThe funnel plot for OS analysis is shown in Figure S1. Egger’s test showed no significant publication bias (P = 0.227).\n\nWe also performed a pooled analysis of studies that included other types of survival analyses. Pooled CSS analysis (n = 4), as seen in Figure S2, showed that patients with EOPC had a better CSS than those with AOPC (HR = 0.85; 95% CI, 0.72–1.00; P = 0.05). Pooled RFS analysis (n = 4), as seen in Figure S3, showed that patients with EOPC had a similar RFS to those with AOPC (HR = 1.10; 95% CI, 0.78–1.54; P = 0.60). The pooled PFS (n = 3), as seen in Figure S4, also showed that patients with EOPC had a similar PFS to those with AOPC (HR = 0.84; 95% CI, 0.61–1.17; P = 0.30). Only one study reported DFS, which showed that patients with EOPC had a worse DFS than those with AOPC (HR = 2.40; 95% CI, 1.13–5.10; P = 0.02).32\n\nOverall survival in patients undergoing surgery\n\nFigure 3 shows the forest plot for studies that performed subgroup OS analyses in patients undergoing surgery (n = 9), the result of which showed that patients with EOPC who underwent surgery had a similar OS to those with AOPC who underwent surgery (aHR = 0.95; 95% CI, 0.84–1.08; P = 0.44).\n\nFigure S5 shows the pooled analysis of the risk ratio (RR) of distant metastasis between patients with EOPC and those with AOPC. Twelve studies were included in the pooled analysis, the results of which showed that patients with EOPC had an increased risk of distant metastasis (stage IV) than those with AOPC (RR = 1.08; 95% CI, 1.03–1.13; P = 0.001).\n\nSurgery\n\nFigure S6 shows the pooled analysis of the RR of the rate of surgery between patients with EOPC and those with AOPC, the results of which showed that patients with EOPC underwent more surgeries than those with AOPC (RR = 1.22; 95% CI, 1.13–1.32; P < 0.001).\n\nChemotherapy\n\nFigure S7 shows the pooled analysis of the RR of the rate of chemotherapy between patients with EOPC and those with AOPC, the results of which showed that patients with EOPC received more chemotherapy than those with AOPC (RR = 1.31; 95% CI, 1.25–1.37; P < 0.001).\n\nRadiotherapy\n\nFigure S8 shows a pooled analysis of the RR of the rate of radiotherapy between patients with EOPC and those with AOPC, the results of which showed that patients with EOPC underwent more radiotherapy than those with AOPC (RR = 1.35; 95% CI, 1.32–1.38; P < 0.001).\n\n\nDiscussion\n\nThe relationship between age at diagnosis and the survival of patients with cancer is complex. Some studies have shown that early-onset breast, lung, central nervous system, and soft tissue cancers are associated with poor prognosis.33,34 Other studies, however, have shown that patients with early-onset cancer had a better OS than those with late-onset cancer, such as colorectal cancer.35 The results of our meta-analysis fall in line with the latter, showing that EOPC patients had better prognosis than AOPC patients. Our findings are in line with the results of most previous studies. For example, Beeghly-Fadiel et al.9 showed that patients with EOPC had a better OS than those with AOPC, independent of other factors. They also showed that the mortality rate increased significantly after the age of 60 years in patients with EOPC. A study by Ordonez et al.14 showed similar results. Although patients with EOPC presented with several risk factors that are typically associated with worse survival (e.g., more advanced stage, male sex, and non-caput tumor), they still had a better OS than patients with AOPC.\n\nSeveral other studies, however, have reported contradictory results. Ansari et al.4 analyzed 72,906 patients with PDAC from the SEER registry, and after propensity score matching, found that patients with EOPC had a shorter CSS than those with AOPC. This result was true even after controlling for other factors, such as cancer stage and treatment received by the patients. They also found that patients with EOPC were also more often diagnosed at more advanced AJCC stages and received more treatments (surgery, radiotherapy, and chemotherapy) than patients with AOPC. Another registry-based study in Japan also found that younger patients had worse survival rates than older patients. Similarly, the aforementioned study showed that younger patients were often diagnosed at more advanced stages than older patients; however, they found that younger patients underwent fewer surgeries and achieved fewer R0 resections than older patients. When subgroup analysis of resected patients was performed, there was no difference in the survival rates between younger and older patients.15 The aforementioned study was not included in the pooled analysis, however, because the survival analysis was not adjusted for cancer stage.\n\nThe pooled analysis in the present study also showed that patients with EOPC had a higher rate of distant metastasis than those with AOPC, a phenomenon which was also observed in previous studies. For example, Tingstedt et al.7 found a higher proportion of distant metastasis in patients with EOPC than in those with AOPC. Eguchi et al.15 found that patients with EOPC had a larger tumor size, liver metastasis, and peritonitis carcinomatosa than those with AOPC. It is still unclear why patients with EOPC are more often diagnosed at an advanced cancer stage compared to patients with AOPC. One potential explanation for this might be the underdiagnosis of cancer in younger patients, as clinicians may be less likely to diagnose rare pathologies in younger patients, particularly in the early stages of the disease. Additionally, younger patients are more likely to present to the hospital at a later stage of the disease, due to a reluctance to seek care early.36 Some studies have hypothesized that patients with EOPC may have a more aggressive tumor phenotype than patients with AOPC due to differences in their molecular profiles.37,38\n\nSeveral studies have compared the molecular profiles of EOPC and AOPC, with mixed results. Bergmann et al.37 investigated the molecular characteristics of 7 patients with PDAC aged ≤ 40 years old, and found that all of the patients exhibited SMAD4 inactivation, which was associated with more aggressive tumors. Surprisingly, they also found that most patients had wild-type KRAS, which is unusual, as KRAS mutations are commonly found in patients with PDAC (90%).16 Wild-type KRAS was also associated with other targetable alterations, such as mismatch repair deficiency.38 In a recent preprint, Ogobuiro et al.39 showed that patients with EOPC with wild-type KRAS tumors had fewer TP53 mutations. Instead, carcinogenesis in EOPC is more likely driven by NRG1 and MET fusions. BRAF fusion was observed only in patients with AOPC with wild-type KRAS. In a subgroup analysis of patients with wild-type KRAS, the patients with EOPC had a better prognosis than those with AOPC; however, there was no difference in the survival of any patients with mutant KRAS. These molecular characteristics might explain the different results of prognostic studies comparing patients with EOPC and those with AOPC. Other studies have also shown a higher rate of mutations in several genes in patients with EOPC compared to patients with AOPC, such as CDKN2A, FOXC2, and PI3KCA.40,41\n\nWhether younger patients had a higher prevalence of pathogenic germline variants (PGVs) than older patients remains unclear. Bannon et al.42 found that patients with EOPC had a higher prevalence of PGVs (most commonly BRCA1/2 and MMR) than patients with AOPC, which was especially true for patients < 42 years old (OR = 4.17; 95% CI, 1.42–11.84; P= 0.011). Castet et al.19 found that 22% of patients from the EOPC group and 13% from the AOPC group had PGVs, the most common of which was BRCA2. However, TP53, PMS2, and MSH6 PGVs were only found in the EOPC group. Additionally, patients with PGVs had a better OS than those without PGVs, independent of other factors. In contrast, Raffene et al.43 found no significant molecular profile differences between the EOPC and AOPC. It is possible that only a certain subset of EOPC patients have distinct molecular profiles than AOPC patients. Intra-tumoral (variability across individual cell populations within a biopsy site) and inter-tumoral heterogeneity (variability across individual cell populations between the primary and the metastatic site) may also be present, which are important confounders in genomic studies.41\n\nDespite showing that patients with EOPC had a higher rate of distant metastasis, the results of the present meta-analysis also showed that patients with EOPC received more treatments than those with AOPC, which might explain why patients with EOPC had longer survival times than those with AOPC, even though they were more often diagnosed at a more advanced stage. This hypothesis was corroborated by a subgroup analysis of patients who underwent surgery, the results of which showed no significant difference in survival between the two groups. This phenomenon has been universally observed in other studies. Saadat et al.6 studied the differences in treatment utilization patterns between patients with EOPC and those with AOPC in the United States. They found that overall, patients with EOPC received more multimodal treatment regimens than those with AOPC, regardless of the cancer stage; therefore, they hypothesized that younger patients would be more willing to seek care, more likely to have private health insurance, have better access to tertiary healthcare centers, and be more fit to undergo treatment. Clinicians were also more willing to prescribe intensive treatments to younger patients because of their longer life expectancies compared to older patients; however, a high percentage of patients with EOPC and AOPC (19% and 39%, respectively) did not receive any treatment. Those who received no treatment tended to be non-White females with no private health insurance, less income, and lower levels of education, suggesting the vital role of the social determinants in the health of patients with PDAC. It is also important to note that most of these studies were conducted in developed countries, whereas patients with EOPC in developing countries may face more barriers to treatment, primarily due to financial hurdles. Younger patients with cancer may have no or inadequate health insurance coverage, limited financial assets, and significant work interruptions, leading to high financial strain.44 Therefore, patients with EOPC in developing countries may have different treatment utilization patterns than those in developed countries.\n\nThe present study has several limitations. First, we only included studies written in English, which may have increased publication bias. Second, there was also substantial heterogeneity between the included studies, possibly due to differences in the age cutoffs for EOPC, study time frames that might have lead to different treatment protocols, and the inclusion of covariates in the survival analysis. Therefore, we performed several sensitivity analyses that yielded similar conclusions. Third, the retrospective design of the included studies also means that some data, such as the specific chemotherapeutic agents used and genetic data, may be difficult to obtain. The present study does, however, have several strengths. First, to the best of the authors’ knowledge, this is the first meta-analysis to compare the survival of patients with EOPC to those with AOPC. Finally, we used multiple statistical methods21,27 to estimate the aHR of several studies to maximize study inclusion and minimize publication bias.\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nNo data associated with this article.\n\nFigshare: Supplementary Tables and Figures. https://doi.org/10.6084/m9.figshare.26130982 45\n\nData is available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: PRISMA checklist and flowchart for ‘The Association between Early-Onset Pancreatic Ductal Adenocarcinoma and Patient’s Survival: A Systematic Review and Meta-Analysis’. https://doi.org/10.6084/m9.figshare.26548492 46\n\nData is available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nFerlay JEM, Lam F, Laversanne M, et al.: Global cancer observatory: Cancer today.2024 [cited 2024 26 Feb]. Reference Source\n\nNIH national cancer institute SEER program: Cancer stat facts: Pancreatic cancer.26 Feb 2024. Reference Source\n\nSung H, Siegel RL, Rosenberg PS, et al.: Emerging cancer trends among young adults in the USA: Analysis of a population-based cancer registry. Lancet Public Health. 2019; 4(3): e137–e147. PubMed Abstract | Publisher Full Text\n\nAnsari D, Althini C, Ohlsson H, et al.: Early-onset pancreatic cancer: A population-based study using the seer registry. Langenbeck’s Arch. Surg. 2019; 404(5): 565–571. PubMed Abstract | Publisher Full Text\n\nPiciucchi M, Capurso G, Valente R, et al.: Early onset pancreatic cancer: Risk factors, presentation and outcome. Pancreatology. 2015; 15(2): 151–155. PubMed Abstract | Publisher Full Text\n\nSaadat LV, Chou JF, Gonen M, et al.: Treatment patterns and survival in patients with early-onset pancreatic cancer. Cancer. 2021; 127(19): 3566–3578. PubMed Abstract | Publisher Full Text\n\nTingstedt B, Weitkämper C, Andersson R: Early onset pancreatic cancer: A controlled trial. Ann. Gastroenterol. 2011; 24(3): 206–212. PubMed Abstract\n\nDai D, Wang Y, Hu X, et al.: Prognostic analysis of very early onset pancreatic cancer: A population-based analysis. PeerJ. 2020; 2020(2).\n\nBeeghly-Fadiel A, Luu HN, Du L, et al.: Early onset pancreatic malignancies: Clinical characteristics and survival associations. Int. J. Cancer. 2016; 139(10): 2169–2177. PubMed Abstract | Publisher Full Text\n\nRamai D, Lanke G, Lai J, et al.: Early- and late-onset pancreatic adenocarcinoma: A population-based comparative study. Pancreatology. 2021; 21(1): 124–129. PubMed Abstract | Publisher Full Text\n\nAbboud Y, Samaan JS, Oh J, et al.: Increasing pancreatic cancer incidence in young women in the united states: A population-based time-trend analysis, 2001-2018. Gastroenterology. 2023; 164(6): 978–89 e6.\n\nMcWilliams RR, Maisonneuve P, Bamlet WR, et al.: Risk factors for early-onset and very-early-onset pancreatic adenocarcinoma: A pancreatic cancer case-control consortium (panc4) analysis. Pancreas. 2016; 45(2): 311–316. PubMed Abstract | Publisher Full Text\n\nUlanja MB, Moody AE, Beutler BD, et al.: Early-onset pancreatic cancer: A review of molecular mechanisms, management, and survival. Oncotarget. 2022; 13: 828–841. PubMed Abstract | Publisher Full Text\n\nOrdonez JE, Hester CA, Zhu H, et al.: Clinicopathologic features and outcomes of early-onset pancreatic adenocarcinoma in the united states. Ann. Surg. Oncol. 2020; 27(6): 1997–2006. PubMed Abstract | Publisher Full Text\n\nEguchi H, Yamaue H, Unno M, et al.: Clinicopathological characteristics of young patients with pancreatic cancer: An analysis of data from pancreatic cancer registry of japan pancreas society. Pancreas. 2016; 45(10): 1411–1417. PubMed Abstract\n\nPark W, Chawla A, O’Reilly EM: Pancreatic cancer: A review. JAMA. 2021; 326(9): 851–862. PubMed Abstract | Publisher Full Text\n\nMoher D, Liberati A, Tetzlaff J, et al.: Preferred reporting items for systematic reviews and meta-analyses: The prisma statement. PLoS Med. 2009; 6(7): e1000097.\n\nRiley RD, Moons KGM, Snell KIE, et al.: A guide to systematic review and meta-analysis of prognostic factor studies. BMJ. 2019; 364: k4597.\n\nCastet F, Fabregat-Franco C, Castillo G, et al.: Clinical and genomic characterisation of early-onset pancreatic cancer. Eur. J. Cancer. 2023; 194.\n\nRen S, Sadula A, Ye C, et al.: Clinical characteristics, treatment patterns and survival outcomes of early-onset pancreatic adenocarcinoma: A population-based study. Am. J. Transl. Res. 2023; 15(1): 407–421. PubMed Abstract\n\nTakeda T, Sasaki T, Inoue Y, et al.: Early-onset pancreatic cancer: Clinical characteristics and survival outcomes: Early-onset pancreatic cancer. Pancreatology. 2022; 22(4): 507–515. PubMed Abstract | Publisher Full Text\n\nWhitley A, Kocián P, Nikov A, et al.: Early-onset pancreatic cancer: A national cancer registry study from the czech republic and review of the literature. J. Hepatobiliary Pancreat. Sci. 2023.\n\nZironda A, Zhang C, Day C, et al.: Early vs conventional onset pancreatic ductal adenocarcinoma: Analysis of surgical and oncologic outcomes in patients undergoing curative intent resection. HPB. 2023.\n\nMendis S, Lipton L, To YH, et al.: Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data. Br. J. Cancer. 2024.\n\nAmin MB: AJCC cancer staging manual. 8th ed.Switzerland: Springer; 2017.\n\nTierney JF, Stewart LA, Ghersi D, et al.: Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007; 8: 16. PubMed Abstract\n\nHebert AE, Kreaden US, Yankovsky A, et al.: Methodology to standardize heterogeneous statistical data presentations for combining time-to-event oncologic outcomes. PLoS One. 2022; 17(2): e0263661. PubMed Abstract | Publisher Full Text\n\nAltman DG, McShane LM, Sauerbrei W, et al.: Reporting recommendations for tumor marker prognostic studies (remark): Explanation and elaboration. BMC Med. 2012; 10: 51.\n\nReview Manager (RevMan): [Computer software] 5.3 ed. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2014. Reference Source\n\nR Core Team: R: A Language and Environment for Statistical Computing. [Computer Software]. Vienna, Austria: 2023. Reference Source\n\nPrometa 3: [Computer software] 3.0 ed. Cesena, Italy: Internovi; 2016. Reference Source\n\nKang JS, Jang JY, Kwon W, et al.: Clinicopathologic and survival differences in younger patients with pancreatic ductal adenocarcinoma—a propensity score-matched comparative analysis. Pancreatology. 2017; 17(5): 827–832. PubMed Abstract | Publisher Full Text\n\nChen HL, Zhou MQ, Tian W, et al.: Effect of age on breast cancer patient prognoses: A population-based study using the seer 18 database. PLoS One. 2016; 11(10): e0165409. PubMed Abstract | Publisher Full Text\n\nHamilton AC, Donnelly DW, Fitzpatrick D, et al.: Early-onset cancers in adults: A review of epidemiology, supportive care needs and future research priorities. Cancers (Basel). 2022; 14(16).\n\nCheng E, Blackburn HN, Ng K, et al.: Analysis of survival among adults with early-onset colorectal cancer in the national cancer database. JAMA Netw. Open. 2021; 4(6): e2112539. PubMed Abstract | Publisher Full Text\n\nMiksad RA, Calip GS: Early-onset pancreatic cancer research: Making sense of confounding and bias. Cancer. 2021; 127(19): 3505–3507. PubMed Abstract | Publisher Full Text\n\nBergmann F, Aulmann S, Wente MN, et al.: Molecular characterisation of pancreatic ductal adenocarcinoma in patients under 40. J. Clin. Pathol. 2006; 59(6): 580–584. PubMed Abstract\n\nVarghese AM, Singh I, Singh R, et al.: Early-onset pancreas cancer: Clinical descriptors, genomics, and outcomes. J. Natl. Cancer Inst. 2021; 113(9): 1194–1202. PubMed Abstract | Publisher Full Text\n\nOgobuiro I, Baca Y, Ribeiro JR, et al.: Multi-omic characterization reveals a distinct molecular landscape in young-onset pancreatic cancer. medRxiv. 2023.\n\nBen-Aharon I, Elkabets M, Pelossof R, et al.: Genomic landscape of pancreatic adenocarcinoma in younger versus older patients: Does age matter? Clin. Cancer Res. 2019; 25(7): 2185–2193. PubMed Abstract | Publisher Full Text\n\nTsang ES, Topham JT, Karasinska JM, et al.: Delving into early-onset pancreatic ductal adenocarcinoma: How does age fit in? Clin. Cancer Res. 2021; 27(1): 246–254. PubMed Abstract | Publisher Full Text\n\nBannon SA, Montiel MF, Goldstein JB, et al.: High prevalence of hereditary cancer syndromes and outcomes in adults with early-onset pancreatic cancer. Cancer Prev. Res. (Phila.). 2018; 11(11): 679–686. PubMed Abstract | Publisher Full Text\n\nRaffenne J, Martin FA, Nicolle R, et al.: Pancreatic ductal adenocarcinoma arising in young and old patients displays similar molecular features. Cancers (Basel). 2021; 13(6).\n\nSalsman JM, Bingen K, Barr RD, et al.: Understanding, measuring, and addressing the financial impact of cancer on adolescents and young adults. Pediatr. Blood Cancer. 2019; 66(7): e27660. PubMed Abstract | Publisher Full Text\n\nRenaldi K, William A: Supplementary tables and figures. [Data File]. Jakarta: Universitas Indonesia; 2024. [cited 10 August 2024]. Publisher Full Text\n\nRenaldi K, William A: Prisma checklist and flowchart for ‘the association between early-onset pancreatic ductal adenocarcinoma and patient’s survival: A systematic review and meta-analysis’. [Data File]. Jakarta: Universitas Indonesia; 2024. [cited 10 August 2024]. Publisher Full Text"
}
|
[
{
"id": "318420",
"date": "11 Sep 2024",
"name": "Yan Wisnu Prajoko",
"expertise": [
"Reviewer Expertise surgical oncology"
],
"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\n1. The topic of this article is quite interesting and updated. because reviewing the prevalence of early onset pancreatic cancer which has increased quite a bit recently, both in developing countries and especially in developed countries.\n\n2. The literature review is also quite complete, but the author himself realizes that there are shortcomings, because it only includes articles written in English.\n\n3. The review method has also been carried out well and systematically\n4. The results are well written and in fairly good English\n5. Even though the results obtained do not provide much clarity, this study can provide additional knowledge about this scientific field or disease.\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": [
{
"c_id": "12419",
"date": "13 Sep 2024",
"name": "Kaka Renaldi",
"role": "Author Response",
"response": "Thank you for the kind comment and for taking time to review our paper."
}
]
},
{
"id": "322276",
"date": "30 Sep 2024",
"name": "Stefania Bunduc",
"expertise": [
"Reviewer Expertise gastroenterology",
"pancreatology",
"pancreatic cancer",
"liquid biopsy",
"meta-analysis"
],
"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 have performed a systematic review and meta analysis evaluating the prognosis differences between early (<= 50 years of age) and average (> 50 years old) onset pancreatic cancer patients.\nThe methodology is sound, reporting is appropriate the idea is new and the findings are relevant while the manuscript is well balanced and very well written. The authors may consider the following minor comments:\nMethods section: The revised PRISMA statement was published in 2020 - although changes are not major the authors may consider reporting based on it PRISMA 2020 statement — PRISMA statement (prisma-statement.org) - was the protocol previously published on PROSPERO? - if yes, please provide CRD - the statistical analysis subsection should be dedicated to explaining how the calculations were performed while the evaluated outcomes - primary and secondary should be reported in a separate subsection\n\nResults: - tables and figures should stand alone abbreviations should be defined in footnotes\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? I cannot comment. A qualified statistician is required.\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/13-976
|
https://f1000research.com/articles/13-973/v1
|
28 Aug 24
|
{
"type": "Study Protocol",
"title": "Sexual side effects of antipsychotic drugs in schizophrenia: Protocol for a systematic review with single-arm, pairwise and network meta-analysis of randomized controlled trials and non-randomized studies",
"authors": [
"Johannes Schneider-Thoma",
"Shimeng Dong",
"Orestis Efthimiou",
"Spyridon Siafis",
"Wulf Peter Hansen",
"Elfriede Scheuring",
"Karl Heinz Möhrmann",
"Stefan Leucht",
"Shimeng Dong",
"Orestis Efthimiou",
"Spyridon Siafis",
"Wulf Peter Hansen",
"Elfriede Scheuring",
"Karl Heinz Möhrmann",
"Stefan Leucht"
],
"abstract": "Introduction Sexual dysfunctions are common yet underreported side effects of antipsychotics for schizophrenia, affecting 30-80% of treated individuals. These side effects can severely impact social interactions and treatment adherence for individuals with schizophrenia, but comprehensive comparative evidence assessing the risk profiles of different antipsychotics is lacking. This study aims to address this gap using network meta-analysis that integrates data from both randomized-controlled trials (RCTs) and non-randomized studies (NRS). Protocol This systematic review will include both RCTs and NRS focusing on participants with schizophrenia or schizophrenia-like psychoses, without restrictions on symptoms, gender, ethnicity, age, or setting. For interventions, all second-generation antipsychotics will be included. The primary outcome will be the occurrence of at least one sexual adverse event of any kind. Secondary outcomes will be the occurrence of any sexual adverse event evaluated in men and women separately, and any adverse event related to the three phases of sexual response cycle separately: desire (e.g. libido, sexual thoughts), arousal (e.g. erection, lubrication) and orgasm (e.g. ejaculation, anorgasmia), and any adverse effect related to breast dysfunction and menstruation irregularities. Study selection and data extraction will be performed independently by two reviewers. The Cochrane Risk of Bias tool 1 and ROBINS-I will be employed to evaluate the risk of bias for RCTs and NRS, respectively. Single-arm meta-analysis of proportions will synthesize the average frequency of sexual adverse events in treated participants. Pairwise and network meta-analysis of RCTs and NRS will be used to evaluate comparative tolerability. Subgroup and sensitivity analyses will explore possible heterogeneity in results and validate the findings’ robustness. The quality of the evidence will be evaluated using GRADE.\n\nDiscussion This study will provide vital insights into the sexual side effects of antipsychotics by combining evidence from clinical trials and real-world practice, facilitating better decision-making in choosing the optimal antipsychotic for individuals.",
"keywords": [
"Sexual side effects",
"antipsychotics",
"schizophrenia",
"meta-analysis"
],
"content": "Introduction\n\nSchizophrenia is a prevalent severe mental illness with worldwide distribution, affecting approximately 1% of the population during their lifetime due to its start during early adulthood (McGrath et al. 2008). Antipsychotics, which are critical for both acute management and prevention of relapse in schizophrenia (DGPPN e.V. for the Guideline Group 2019), are often prescribed over long periods, potentially lifelong. These medications, however, are associated with various side effects, including sexual dysfunctions.\n\nSexual dysfunctions induced by antipsychotics can manifest as disturbances in sexual desire, erection and ejaculation, vaginal lubrication, and orgasmic dysfunctions as well as partly related disorders of the menstruation cycle and the breast (such as gynecomastia and galactorrhea) (Kelly and Conley 2004; La Torre et al. 2013; Montejo et al. 2018). These dysfunctions are not only common —mostly reported in 30-80% of treated individuals with prevalence rates varying from 0 to over 90% (La Torre et al. 2013) —but also highly distressing and a frequent cause of non-adherence to treatment (Perkins 2002; Lambert et al. 2004). Non-adherence significantly elevates the risk of relapse of psychotic symptoms. Moreover, sexual side effects critically interfere with normal participation in social life in terms of having close and satisfying personal relations in a romantic partnership, which is one of the most important unmet needs of individuals with schizophrenia (Jager and McCann 2017). Therefore, sexual side effects severely diminish the quality of life for those affected (Bebbington et al. 2009; Olfson et al. 2005).\n\nDespite the significant clinical impact of sexual side effects induced by antipsychotics, there is a lack of comprehensive meta-analyses addressing this critical issue, particularly no network meta-analyses presenting differences between antipsychotics in this regard. Existing reviews include several narrative reviews and some pairwise meta-analyses (mainly Cochrane reviews) that only focused on specific antipsychotics and invested sexual side effects as secondary outcomes (risperidone (Hunter et al. 2003; Jayaram and Hosalli 2005; Komossa et al. 2011), sertindole (Komossa et al. 2009; Lewis et al. 2005), paliperidone (Harrington and English 2010), or amisulpride (Men et al. 2018)). Moreover, some meta-analyses only included observational studies (Zhao et al. 2020; Korchia et al. 2023) or had a small number of studies (Trinchieri et al. 2021). One single-arm meta-analysis combined both randomized and observational data and calculated overall percentages of sexual dysfunctions with each antipsychotic across 34 studies (Serretti and Chiesa 2011). However, as the authors report themselves, this approach is not suitable to make statements for differences between antipsychotics in propensity to cause sexual side effects. In summary, the existing evidence leaves us with an incomplete and only impressionistic picture which is limited in terms of available trials, number of events and use of inappropriate methods.\n\nThis study aims to fill this knowledge gap by providing evidence-based insights on sexual adverse events associated with antipsychotic to guide the selection of the optimal drug for individual needs. Therefore, to summarize according to the PICO(S) scheme, we will conduct a comprehensive network meta-analysis combining data from randomized-controlled trials and real-world observational studies (Study design) to compare all second-generation antipsychotics (Intervention) with each other (Comparator) on their propensity to cause sexual side effects (Outcome) in patients with schizophrenia (Population).\n\n\nMethods\n\nWe report this systematic review and network meta-analysis protocol according to the Preferred Reporting Items for Systematic review and Meta-analysis Protocols (PRISMA-P) checklist, and the PRISMA extension for network meta-analysis (Hutton et al. 2015). The PRISMA-P Checklist can be found in the extended data. This protocol has been registered with PROSPERO (registration number: CRD42024510190) and will be updated with any necessary amendments.\n\nStudy designs\n\nWe will include randomized controlled trials (RCTs) and non-randomized studies (NRS). RCTs identified with high risk of bias in sequence generation will be considered as quasi-randomized studies and grouped with NRS. The inclusion of NRS is not limited to specific study designs because as stressed by the Cochrane handbook (Reeves et al. 2022), design labels are used very inconsistently and the risk of bias of a certain NRS can be only assessed when the specific study features are known. Accordingly, studies will first be classified by design, followed by a careful assessment of bias risk for each study and studies with critical risk of bias will be excluded from the analysis. We will also exclude studies from mainland China that are not conducted by international pharmaceutical companies or published in international scientific journals due to significant concerns regarding methodological and reporting quality (Leucht et al. 2022). Both open-label and blinded studies will be included; however, open-label and single-blind studies will be excluded in a sensitivity analysis to address potential bias in expectations of sexual side effects. The minimum study duration will be 3 weeks because shorter studies usually do not focus on clinical efficacy and tolerability of antipsychotics but on more experimental research questions. For cross-over studies, only data from the first phase will be used to avoid carry-over effects, which are common in schizophrenia.\n\nParticipants\n\nWe will include trials in which at least 80% of the participants are diagnosed with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) without restrictions in terms of symptoms (acute episode or maintenance phase), gender, ethnicity, age, or setting. These inclusion criteria are adopted because occurrence of side effects can be considered largely independent of psychopathology and they will increase the data availability for these typically underreported outcomes (Zorzela et al. 2016). Of note, we will record potentially important population characteristics for each trial and consider them in the assessments of heterogeneity and transitivity ae well as in subgroup and sensitivity analyses.\n\nInterventions\n\nAll second-generation antipsychotics (SGAs), which are predominantly prescribed for schizophrenia in Europe, Japan and the USA, will be included in this study, namely amisulpride, aripiprazole, asenapine, blonanserine, brexpiprazole, cariprazine, clozapine, iloperidone, lumateperone, lurasidone, olanzapine, olanzapine-samidorphan, paliperidone, perospirone, quetiapine, risperidone, sertindole, ziprasidone, zotepine. Only SGAs are included because those were investigated in recent clinical research adhering to standardized procedures. These standards include systematic documentation of adverse events according to protocols like the Good-Clinical-Practice guideline and use of standardized nomenclatures of adverse events such as MedDRA (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 2022). Furthermore, reporting of studies involving SGAs typically comply with guidelines like CONSORT for RCTs (Schulz et al. 2010) and STROBE for NRS (Vandenbroucke et al. 2007), ensuring detailed information on study design and outcomes. Moreover, study authors and pharmaceutical companies of these trials are very likely to keep electronic records and are contactable to provide necessary additional information, which is very important for this review. However, we will include first-generation antipsychotics (FGAs), placebo and no treatment when they were used as comparators in RCTs and NRS of SGAs.\n\nWe will include all these compounds, when used in monotherapy, in any form of administration (e.g. oral or intramuscular depot). Primarily, different applications of the same drug will be combined because side effects predominantly follow the pharmacodynamic profile of the specific compounds and not its pharmacokinetics, as observed in previous reviews (Huhn et al. 2019; Schneider-Thoma et al. 2022), but considered separate interventions in sensitivity analysis. For RCTs, we will only include fixed-dose studies within the target to maximum range according to a recent consensus reached after a two-step Delphi survey among international experts in the treatment of schizophrenia (McAdam et al. 2023); all flexible-dose treatment regimens (as long as they overlap with the target to maximum range) will be included as these allow investigators to titrate doses to optimal levels for individual participants. Similarly, NRS that rely on observed clinical data will be treated as having flexible dose. In sensitivity analyses, we will exclude flexible dose RCTs and NRS in which the applied doses were outside the target to maximum range for some participants, to control for potential effects of extremely low or high doses.\n\nComparators\n\nIn network meta-analysis there is no formal comparator as all interventions will be compared with each other.\n\nOutcome measures\n\nPrimary outcome\n\nThe primary outcome will be “Any sexual side effect”. We will use the occurrence of at least one sexual adverse event of any kind provided by the original authors, for example from specific questionnaires for sexual side effects. In case the occurrence of any sexual side effect is not explicitly reported, we will use the highest number of participants reported for any specific sexual adverse event, in line with methodologies used in previous reviews (Serretti and Chiesa 2011; Huhn et al. 2019; Schneider-Thoma et al. 2022).\n\nSecondary outcomes\n\n1. Any sexual adverse event in men and women separately.\n\n2. Any adverse events related to the “desire” phase of sexual response cycle, such as libido decrease, loss of sexual thoughts.\n\n3. Any adverse events related to the “arousal” phase of sexual response cycle, such as erectile dysfunction, vaginal lubrication decrease.\n\n4. Any adverse events related to the “orgasm” phase of sexual response cycle, such as ejaculation dysfunction, anorgasmia.\n\n5. Any adverse related to breast dysfunction, such as gynecomastia, galactorrhea.\n\n6. Any adverse related to menstruation irregularities, such as amenorrhea.\n\nOf note, there is discussion whether breast dysfunction and menstruation irregularities should be considered as sexual side effects because they are not part of the sexual function per se. However, they are frequently mentioned in parallel to dysfunctions of the sexual response cycle, included in some scales for sexual side effects (Serretti and Chiesa 2011; Boer et al. 2014) and very bothersome for participants, and therefore we decided to address them as secondary outcomes.\n\nTiming\n\nTiming of outcome measurement will be at study endpoint.\n\nElectronic searches\n\nAs recommended by the PRISMA harms checklist (Zorzela et al. 2016) and the Cochrane handbook (Reeves et al. 2022), we search for any study that might have reported adverse events in general and not only for studies mentioning specific sexual adverse events in title/abstract because it is impossible to report all adverse events in searchable/indexable parts of publications. For RCTs, we search the Cochrane Schizophrenia Group’s Study-Based Register of trials (Shokraneh and Adams 2020) for published and unpublished reports. Following the methods from Cochrane (Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA 2022) the Information Specialist compiles this register from systematic searches in MEDLINE, Embase, Allied and Complementary Medicine (AMED), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, PubMed, US National Institute of Health Ongoing Trials Register ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ProQuest Dissertations and Theses A&I. The register also includes hand searches and conference proceedings and does not place any limitations on language, date, document type or publication status. For NRS, we search multiple electronic databases including ClinicalTrials.gov, Embase, MEDLINE, PsycINFO, Science Citation Index-Expanded, and WHO International Clinical Trials Registry Platform (ICTRP) with no date/time, language, document type, and publication status limitations. The search string contains terms for schizophrenia and the included antipsychotics. The detailed search strategies can be found in the extended data.\n\nReference lists and other sources\n\nAs additional hand searches, we will check the included studies in previously published relevant systematic reviews. Moreover, because adverse events are often underreported, we will contact the corresponding authors of each included study for unpublished information about adverse events.\n\nUsing Rayyan (Ouzzani et al. 2016), title and abstracts of identified references are screened in duplicate by two reviewers with regard to the eligibility criteria above. Any disagreements between the two reviewers are solved by discussion. Then, again in duplicate, two reviewers will inspect the full articles of references selected in title/abstract screening for eligibility and for availability of sexual side effects. Any disagreements will be solved by discussion among the two reviewers or with a third, experienced reviewer (JST, SL). If a decision cannot be made, the study authors will be contacted for clarification.\n\nTwo reviewers will independently conduct data extraction in an established server-based Microsoft Access database designed for the specific needs of blind data entry by two reviewers and automatic double check of extracted data. Data extraction will be piloted on a random sample of ten RCTs and ten NRS. In case of disagreement, a decision will be reached by discussing with a third reviewer (JST, SL) or by contacting the study authors. Data on the following points will be collected:\n\n− General information, such as author name, year of publication, treatment arms and sample size.\n\n− Methodology, such as study design, blinding, duration of study, diagnostic criteria used, study population (Intention-to-treat, observed cases) for which adverse events are reported.\n\n− Participant characteristics, such as age, weight, number of men/women, diagnosis details, plasma prolactin level.\n\n− Intervention characteristics, such as doses, form of application, percent co-medication with antidepressants.\n\n− Outcome measures.\n\nRisk of bias will be assessed for each included study by two reviewers in duplicate referring to the Cochrane Collaboration’s risk of bias tools for randomized controlled studies (RoB tool 1) and non-randomized studies (Risk Of Bias In Non-randomized Studies – of Interventions, ROBINS-I). Disagreements in the assessment will be discussed among the two reviewers and, if needed with a third, experienced reviewer (JST, SL). We will exclude NRS judged as carrying an overall critical risk of bias from the primary analysis. RCTs judged at high risk of bias RCTs and NRS judged at serious risk of bias, we will exclude in a sensitivity analysis.\n\nOverview of the step-wise process for data synthesis of randomized and non-randomized data\n\nFirst, we will conduct frequentist random effects single-arm and pairwise meta-analyses with RCTs and NRS as subgroups to synthesize estimates of overall prevalence and comparative tolerability and to assess heterogeneity. In the next step, we will conduct network meta-analysis of RCTs (including assessment of transitivity and evaluation of consistency). If the network meta-analysis of RCTs is internally consistent, we proceed with comparing the different estimates from RCTs (direct, indirect, mixed evidence) to the estimates of NRS. If there are no indications for systematic differences between RCT and NRS estimates, we proceed with combined network meta-analysis (again including assessment of transitivity and inconsistency).\n\nOf note, if the requirements for network meta-analysis of RCTs or joint network meta-analysis of RCTs and NRS are not met, we will not proceed to the next step and use pairwise meta-analysis or network meta-analysis of RCTs for data synthesis.\n\nDetails of synthesis\n\nEstimation procedures\n\nFor estimating the proportion of patients experiencing side effects in antipsychotics, we will use the number of participants experiencing sexual adverse events and non-events among pa exposed to antipsychotics or placebo/no treatment. We will meta-analyze the data using generalized linear mixed models (Schwarzer et al. 2019).\n\nFor comparative pairwise and network meta-analysis, the number of participants experiencing sexual adverse events will be synthesized using odds ratios (OR) because ORs have better mathematical properties for meta-analysis, particularly in the case of studies with varying prevalence rates (Doi et al. 2022) and because it is the only measure available in case-control studies. If available in the original publication, we will use reported ORs that are adjusted for possible confounders, such as differences in age and sex between the compared groups. If not available, we will calculate ORs based on the number of participants with events and the number of participants assessed (considering that some sexual adverse events only occur in men or women).\n\nFor the pairwise meta-analysis we aim to use a random effects meta-analysis model. However, if the data are sparse, i.e. if there are many studies with few or zero events in one or more of their arms, the usual inverse variance model for meta-analysis has limitations. In that case we will use models that can better handle rare events, such as the Mantel-Haenszel model and Bayesian approaches, as per methodological recommendations (Efthimiou 2018).\n\nNetwork meta-analysis of RCTs will be performed in a frequentist framework using a random effects model. We will assume a common heterogeneity parameter across the various treatment comparisons. For combined network meta-analysis of RCTs and NRS, different several statistical models are available. The selection of the most suitable model will be decided after careful consideration of the actual data, the distribution of studies by designs and the risk of bias assessment (Efthimiou et al. 2017). In case of sparse data, we will explore the use of a Bayesian model or a frequentist model based on the Mantel-Haenszel approach (Efthimiou et al. 2019).\n\nAssessment of heterogeneity\n\nHeterogeneity (variability in relative treatment effects within the same treatment comparison) will be assessed within and across study designs by visual inspection of forest plots and estimating the statistical heterogeneity τ, i.e. the standard deviation of random effects, and I2. We will employ empirical distributions to characterize the amount of heterogeneity as low, moderate or high (Turner et al. 2012). Substantial heterogeneity indicates important differences in clinical and methodological characteristics of the studies which warrant further investigation, such as checking for mistakes in data entry and for potential effect modifiers and bias factors. Moreover, to assess how much heterogeneity affects the clinical interpretation of the relative treatment effects with respect to the extra uncertainty anticipated in a future study, we will produce prediction intervals.\n\nAssessment of the transitivity assumption in network meta-analysis\n\nJoint analysis of treatments can be misleading if the network is substantially intransitive. Intransitivity can arise when design, population or treatment characteristics that may modify the relative effects between interventions are distributed differently between comparisons. For the case of relative treatment effects in terms of sexual side effects, there is no clear a-priori-evidence, but several characteristics, may play a role (e.g. study design, blinding, gender, age, dose, antidepressant co-medication). Therefore, we will investigate if relevant characteristics are similarly distributed across studies grouped by comparison.\n\nAssessment of inconsistency\n\nConsistency, i.e. the agreement between direct evidence and indirect evidence of a network meta-analysis, will be statistically evaluated globally, by using the design-by-treatment test (Higgins et al. 2012) and locally, via the back-calculation method (König et al. 2013). In case of evidence of inconsistency, we will investigate possible sources of it (mistakes in data entry, clear differences in study characteristics).\n\nInvestigation of heterogeneity and inconsistency\n\nSubstantial heterogeneity, intransitivity or inconsistency will prevent network meta-analysis. Small or moderate amounts will be further explored by subgroup, network meta-regression, and sensitivity analyses.\n\nWe a priori plan to investigate the impact of following potential effect modifiers via Bayesian network meta-regression analyses of the primary outcome: percentage women, mean age, prolactin level, percent co-medication with antidepressants (which also cause sexual side effects), and duration of study. Additionally, we will perform separate network meta-analyses for sexual adverse events occurring in men and women (see secondary outcome).\n\nMoreover, we will explore the robustness of results (with regard to the inclusion of studies with differences in study design, population and intervention characteristics in the primary analysis) by sensitivity analyses. The following sensitivity analyses of the primary outcomes are predefined: exclusion of (1) non-double-blind studies, (2) studies that report only observed-case analyses, (3) RCTs with high risk/NRS with serious risk of bias, (4) flexible-dose studies in which the range of applied doses exceeded the recommended (target to maximum) dose range (McAdam et al. 2023), (5) studies that did not use specific questionnaires to assess sexual side effects, (6) studies in acutely ill patients (because acute psychosis might interfere with sexual functioning). Moreover, we will perform network meta-analysis with oral and depot applications of the same compound as separate interventions.\n\nSmall study effects and publication bias\n\nFor assessment of small study effects and publication bias, we will employ a comparison-adjusted funnel plot method to explore the association between study size and effect size (Chaimani and Salanti 2012). Moreover, comparisons with 10 or more studies will be plotted in a contour-enhanced funnel plot (Peters et al. 2008). Similarly, we will plot a contour enhanced funnel plot of all SGAs combined versus placebo.\n\nAssessment of the confidence in estimates\n\nThe quality of the evidence of the primary outcome will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework extended to NMA (Puhan et al. 2014).\n\nStatistical software\n\nAnalyses will be performed in R using the packages “meta” for single-arm and pairwise meta-analysis (Balduzzi et al. 2019), “netmeta” for network meta-analyses (Rücker et al. 2020), “crossnma” for combined network meta-analyses of RCTs and NRS (Hamza and Salanti 2022). Bayesian analyses will be performed using self-programmed routines in “rjags” (Plummer et al. 2023). R software and the mentioned packages are freely available https://cran.r-project.org/bin/windows/base/\n\nStudy status: search and the selection process are ongoing currently.\n\n\nDiscussion\n\nDespite its significant clinical relevance, there is a lack of scientific comparison between different antipsychotics regarding their sexual side effects. This project will address this gap by providing a comprehensive synthesis of evidence from clinical trials and real-world clinical practice. This information is relevant for clinicians and guideline developers in selecting the most appropriate medication for individuals. Additionally, this review is of high importance for future clinical research, regarding both RCTs and NRS, as it will report the current state of evidence concerning sexual side effects of antipsychotics and identify existing limitations. Finally, this review will be among the first to integrate randomized and non-randomized evidence in a network meta-analysis, thereby advancing methodological approaches in evidence-based medicine.\n\n\nPatients and public involvement\n\nWe collaborate with members of the patient organization “BASTA - Bündnis für psychisch erkrankte Menschen” and the relatives’ organization “Landesverband Bayern der Angehörigen psychisch erkrankter Menschen e.V.” in this project. They contributed in identifying the research idea and developing this review protocol from their perspective as people with lived experience with the disease schizophrenia and the treatment with antipsychotics. They will be updated regularly about the state of the project and help with any upcoming questions. Moreover, they will be involved in interpreting the results and in preparing a lay summary of the results so that other patients and relatives of patients can be directly informed about the scientific results with a text that can be understood, e.g. using the BASTA-newsblog (http://www.bastagegenstigma.de/).\n\nThis review does not require ethical approval.\n\nSL is the principal investigator, obtained funding, and supervises the study. JST, SD, SS and SL designed the study and provided clinical and methodological advice. JST and SD drafted the manuscript and registered the protocol with PROSPERO before. OE provided substantial methodological and statistical advice. WPH, ES and KHM provided the patient perspective when designing the study. All authors critically reviewed the manuscript for important intellectual content and approved its final version.",
"appendix": "Data availability\n\nNo data associated with this article.\n\nFigshare: Sexual side effects of antipsychotic drugs in schizophrenia: Protocol for a systematic review with single-arm, pairwise and network meta-analysis of randomized controlled trials and non-randomized studies, https://doi.org/10.6084/m9.figshare.26396275.v2 (Dong, 2024).\n\nThe project contains following data:\n\n• PRISMA-p checklist\n\n• Search strategy\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 Dr Farhad Shokraneh, Systematic Review Consultants LTD, for designing the searches and AR, who wants to stay anonymous, for providing the patient perspective in the design of this review.\n\n\nReferences\n\nBalduzzi S, Rücker G, Schwarzer G: How to perform a meta-analysis with R: a practical tutorial. Evid. Based Ment. Health. 2019; 22(4): 153–160. 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Publisher Full Text\n\nOuzzani M, Hammady H, Fedorowicz Z, et al.: Rayyan-a web and mobile app for systematic reviews. Syst. Rev. 2016; 5(1): 210. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPerkins DO: Predictors of noncompliance in patients with schizophrenia. J. Clin. Psychiatry. 2002; 63(12): 1121–1128. Publisher Full Text\n\nPeters JL, Sutton AJ, Jones DR, et al.: Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J. Clin. Epidemiol. 2008; 61(10): 991–996. PubMed Abstract | Publisher Full Text\n\nPlummer M, Stukalov A, Denwood M: rjags: Bayesian Graphical Models using MCMC.2023. Publisher Full Text\n\nPuhan MA, Schünemann HJ, Murad MH, et al.: A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ (Clinical Research ed.). 2014; 349: g5630. Publisher Full Text\n\nReeves BC, Deeks JJ, Higgins JPT, et al.: Chapter 24: Including non-randomized studies on intervention effects.Higgins JPT, Thomas J, Chandler J, et al., editor. Cochrane Handbook for Systematic Reviews of Interventions. version 6.3. 2022.\n\nRücker G, Krahn U, König J, et al.: netmeta: Network Meta-Analysis using Frequentist Methods. R package version 1.2-1.2020. Reference Source\n\nSchneider-Thoma J, Chalkou K, Dörries C, et al.: Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysis. Lancet. 2022; 399(10327): 824–836. PubMed Abstract | Publisher Full Text\n\nSchulz KF, Altman DG, Moher D: CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann. Intern. Med. 2010; 152(11): 726–732. 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}
|
[
{
"id": "319278",
"date": "20 Sep 2024",
"name": "Sofia Brissos",
"expertise": [
"Reviewer Expertise Schizophrenia",
"psychosis",
"forensic psychiatry"
],
"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 focus on an important aspect of schizophrenia patients' treatment, but again, they will focus on data that has been previously collected, which may not be sufficient. For instance, the majority of these clinical trials have a small number of female patients, and many real-life patients have been excluded due to the \"rigorous\" inclusion criteria. Nevertheless, I am happy to see that the authors will conduct independent analysis in men and women separately. In that sense, although the authors plan to include real-world observational studies, we will have access to the reported side-effects of those studies only. Finally, I myself do not find of great interest a manuscript on what will be done; I think what is of interest to the reader is the result of what the authors are planning to analyze, and not just their intentions.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Partly\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": []
},
{
"id": "332301",
"date": "12 Nov 2024",
"name": "Angel L Montejo",
"expertise": [
"Reviewer Expertise Sexuality and Mental Health",
"Psychotropic-related sexual dysfunction",
"Pharmacology"
],
"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 a protocol devised by an expert team with extensive experience in this field. This is a clinical problem of great relevance in psychiatric practice and its strength lies in the fact that there is no comparative study among all the antipsychotics marketed. The results will undoubtedly be of great interest and will provide new information on the meta-analyses already carried out in this field. However, there are still important difficulties to avoid challenges in obtaining reliable information excluding some important confounding factors. The first is that clinical trials of antipsychotics almost never include validated questionnaires to measure sexual dysfunction and rely on spontaneous patient communications, which tends to underestimate the frequency of sexual dysfunction. The second is that many studies on the subject do not consider only those patients who have previous sexual function versus those who are sexually inactive, which may contribute to underestimating the frequency of sexual dysfunction as well. The third is that the high frequency of comorbidity and the use of concomitant treatments seriously bias the results, especially with the use of serotonergic and euthymizing compounds such as lithium, carbamazepine and valproate, which are related to high frequencies of sexual dysfunction. It would be important for the authors to take these limitations into account to find the differences in actual clinical practice between antipsychotics. Finally, because gynecomastia, galactorrhea and amenorrhea are not in themselves part of sexual function but are adverse effects that require adequate attention, I think the title should be changed to another such as: Sexual and endocrinological side effects of antipsychotic drugs in schizophrenia.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Partly\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/13-973
|
https://f1000research.com/articles/12-280/v1
|
14 Mar 23
|
{
"type": "Research Article",
"title": "Improving genomic prediction of rhizomania resistance in sugar beet (Beta vulgaris L.) by implementing epistatic effects and feature selection",
"authors": [
"Thomas Martin Lange",
"Felix Heinrich",
"Friedrich Kopisch-Obuch",
"Harald Keunecke",
"Mehmet Gültas",
"Armin O. Schmitt",
"Thomas Martin Lange",
"Felix Heinrich",
"Friedrich Kopisch-Obuch",
"Harald Keunecke"
],
"abstract": "Background: Rhizomania counts as the most important disease in sugar beet Beta vulgaris L. for which no plant protection is available, leaving plant breeding as the only defence strategy at the moment. Five resistance genes have been detected on the same chromosome and further studies suggested that these might be different alleles at two resistance clusters. Nevertheless, it was postulated that rhizomania resistance might be a quantitative trait with multiple unknown minor resistance genes. Here, we present a first attempt at genomic prediction of rhizomania resistance in a population that was genotyped using single nucleotide polymorphism (SNP) markers. Methods: First, genomic prediction was performed using all SNPs. Next, we calculated the variable importance for each SNP using machine learning and performed genomic prediction by including the SNPs incrementally in the prediction model based on their variable importance. Using this method, we selected the optimal number of SNPs that maximised the prediction accuracy. Furthermore, we performed genomic prediction with SNP pairs. We also performed feature selection with SNP pairs using the information about the variable importance of the single SNPs. Results: From the four methods under investigation, the latter led to the highest prediction accuracy. These results lead to the following conclusions: (I) The genotypes that were resistant at all known resistance genes, provided the highest possible variation of virus concentrations that the machine can measure. Thus, it can be assumed that more genes must be involved in the resistance towards rhizomania. (II) We show that prediction models that include SNP interactions increased the prediction accuracy. Conclusions: Altogether, our findings suggest that rhizomania resistance is a complex quantitative trait that is affected by multiple genes as well as their interaction.",
"keywords": [
"Epistasis",
"genomic prediction",
"machine learning",
"rhizomania",
"resistance breeding",
"Beet necrotic yellow vein virus",
"variable importance"
],
"content": "Introduction\n\nSugar beet (Beta vulgaris L.) is an important crop to secure production of white sugar, especially in industrialised countries.1 In general, sugar beet makes up 20% of the sugar production in the world.2 Next to high sugar yield, resistance to diseases, of which rhizomania is the most significant, is the main goal of sugar beet breeding.3\n\nRhizomania is caused by the Beet necrotic yellow vein virus (BNYVV)4 and is transmitted via the fungus Polymyxa betae Keskin.5,6 Severe infection with rhizomania can cause a reduced sugar yield of up to 90%.7 Moreover, Abe and Tamada (1986) have shown that rhizomania can persist in resting spores of P. betae for over fifteen years, making a decontamination through an enlarged crop rotation nearly impossible.8 Furthermore, there is no pesticide available for plant protection,9 leaving resistance breeding as the only defence strategy at the moment.10\n\nSince the first observation of rhizomania in 1951 in northern Italy, the disease has spread globally and occurs nowadays in all major sugar beet growing regions in the world.11 While strain groups of BNYVV with four ribonucleic acid (RNA) strands are spread globally,12 BNYVV strains with five RNA strands have been found in certain regions in France,13 Japan,14 the UK,15 Kazakhstan,16 and Turkey.7 Comparisons between their pathogenicities revealed that pathotypes of BNYVV with five RNA strands showed significantly higher levels of infection in partially resistant sugar beet varieties than pathotypes with four RNA strands.17\n\nThe first breeding projects against rhizomania started in 197018 and resulted in the publication of three resistance genes in 1987 called “Rizor”,19 “Holly”,20 and “WB42”.20 Nevertheless, further analyses of the resistance genes “Rizor” and “Holly” indicated that these are probably the same gene, henceforth called “Rz1”.21 The resistance gene “WB42” which is also often referred to as “Rz2”, however, was assumed to be a further resistance gene independent from Rz1 with an approximate distance of 20 cM between Rz1 and Rz2.22 Recent studies could not only prove the existence of the Rz2 resistance gene in wild relatives of sugar beet but also found a stop codon in Rz2 in susceptible genotypes which was not present in resistant genotypes.23 In the following years, three further resistance genes were published called “Rz3”,24 “Rz4”,25 and “Rz5”.26\n\nAlthough five resistance genes against rhizomania have been published, doubts have been raised on whether all resistance genes are in fact separate genes or rather alleles of the same genes. All five resistance genes were located on chromosome three18,25,26 where mainly two clusters emerged.27 McGrann et al. (2009) assumed that the resistance against rhizomania may be mainly explained by two loci, with the first locus being represented by Rz1, Rz4, and Rz5, and the second locus being represented by Rz2 and Rz3.12 Although only two resistance clusters against rhizomania are known, it is assumed that rhizomania resistance is a quantitative trait caused by multiple loci with different effects, which have not yet been identified.18\n\nIn general, it has also been postulated that asymmetric variation in quantitative traits can be caused by epistasis.28 Epistasis can be defined as non-additive interaction between genes.29 Theoretically, this interaction can be formed by more than two genes but the analysis of an interaction between more than two genes is challenging due to the computational complexity and the requirement to have large enough samples for each subgroup.30 Although it has been demanded to analyse epistasis in complex trait studies31,32 and epistasis has been analysed for a multitude of traits in sugar beet,33 such a study has not yet been conducted for rhizomania resistance to the best of our knowledge.\n\nIt is generally assumed that a plant’s resistance towards diseases is quantitative and caused by a complex network of multiple loci.34,35 In such cases, genomic prediction is a useful tool to predict an individual’s resistance towards the disease. Such studies have been performed, for example, in soy bean,36 barley,37 rapeseed,38 rice,39 wheat,40 and maize.41,42 Although rhizomania resistance is believed to be a complex trait caused by multiple loci, genomic prediction of rhizomania resistance has not yet been published. Here, we present the first study of genomic prediction of rhizomania resistance with 9,127 single nucleotide polymorphism (SNP) markers in a sugar beet population that is assumed to carry the known resistance genes (Rz1 and Rz2).\n\nOur aim is to maximise the accuracy of genomic prediction of rhizomania resistance in sugar beet. Therefore, we performed genomic prediction using random forest with all available SNP markers. Moreover, we estimated the variable importance of each SNP and, subsequently, performed incremental feature selection to optimise the prediction model by only including an optimal set of SNPs. Furthermore, we used the SNP markers to create SNP pairs and performed genomic prediction with the SNP pairs instead of the single SNPs. Finally, we used the information about the variable importance of each single SNP to create SNP pairs with only the best SNP markers and selected the optimal set of SNPs for genomic prediction with SNP pairs. We provide an R script as well as the data from this trial to encourage researchers to perform feature selection with SNP pairs in their studies. The R script as well as the data from this trial have been published in version v1.0 at https://github.com/tmlange/IFS\\_SNPpairs.git.43\n\n\nMethods\n\nThe greenhouse test was performed with 156 genotypes. For each genotype, 15 plants were grown. Therefore, sugar beet lines were used which were created by crossing two sugar beet lines and self-pollinating the resulting hybrids two times. From the resulting seeds, 15 were chosen from each of the S2 plants as seeds for this trial and the genotype of the parent was assumed as the genotype of each of the seedlings. Thus, the parent was analysed using a SNP chip and the genomic data were used for the descendants. From the 156 genotypes that were used in this trial, 155 genotypes carried the resistance at the two known genes in homozygous form. Thus, it can be assumed that the descendants from these plants must carry the resistance in a homozygous form as well. One genotype, however, was susceptible at Rz2. Also here, it can be assumed that the descendants from this plant must be susceptible in a homozygous form.\n\nPlants were grown for ten weeks in the greenhouse in soil infested with BNYVV, pathotype P. This variant of BNYVV contains five RNA strands44 and is, thus, assumed to be more aggressive than the variants with four RNA strands.17 After ten weeks, plants were removed from the soil and plant sap from lateral roots was extracted. Afterwards, the optical density (OD) value of each sample was measured using the double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). The OD values were measured after 60 minutes, 90 minutes, and 120 minutes using the Infinite F50® (Tecan Group AG, Männedorf, Switzerland) at a wavelength of 405 nm. Harvest, sample preparation and conduction of the DAS-ELISA test followed the protocol described in.45\n\nAlthough DAS-ELISA is an often used tool to measure the concentration of BNYVV in samples from sugar beet,7,10,23 it does not directly measure the virus concentration in form of the OD values.46 To estimate the virus concentrations from the raw OD values as well as to reduce measurement errors for each 96-well plate, we transformed the non-normally distributed raw data to normally distributed data with an inverse logistic regression model.47 Therefore, a logistic regression model was derived using a serial dilution with 12 samples on each 96-well plate. The transformation followed the protocol in Ref. 47 with one adjustment: The ODs were not only measured after 90 minutes but also after 60 and 120 minutes. Thus, each sample had three OD measurements and three transformed measurements. As described in Ref. 47, it can be assumed that the transformed data are normally distributed. Thus, the mean of the transformed data has been calculated and used as response variable to reduce technical errors during measurement at each time point. A statistical model was fit to the data points in the serial dilution and, subsequently, OD values were transformed according to equation 1:\n\nAfter the data set was transformed, the mean of the transformed data was calculated for all plants which were descendants of the same parent. Thus, if no plants died during the trial, the mean from 15 plants was calculated as the phenotypic data point for the corresponding genotype.\n\nAfter transformation and calculating the mean of the transformed values, the SNPs were prepared. For this, SNPs with missing values were removed from the data set. Moreover, redundant SNPs were removed through linkage disequilibrium pruning. In this step, one of two SNPs that were correlated with more than an r2 of 0.95 was removed. This step should ensure that epistasis results were not confounded by linkage disequilibrium.32,48 Furthermore, SNPs with a major allele frequency of 0.95 or higher were removed. After the final step of SNP filtering, 9,127 SNPs were kept in the data set. Furthermore, since only one of the 155 genotypes was susceptible at Rz2, it can be assumed that the SNPs in high linkage disequilibrium with Rz2 must have been removed in the last step of filtering.\n\nFinally, the remaining SNPs were recoded as 0 (homozygous major allele), 2 (homozygous minor allele), and 1 (heterozygous). This kind of coding was recommended for analysing genotypic and additive genetic models.49 All filtering steps and the recoding of the SNPs were performed using PLINK v1.90b6.10.50\n\nAfter data were prepared, genomic prediction was performed using single SNPs. Therefore, the data set was divided randomly into 80% training data (125 data points) and 20% test data (31 data points). Following the experimental design in other studies that used feature selection,51 this process was repeated 10 times. Subsequently, genomic prediction was performed using random forest. To do so, the R package ranger, version 0.14.1 was used with default settings.52\n\nPrediction accuracy was evaluated by prediction of the test data set with a prediction model that was derived using the training data set. Subsequently, the coefficient of determination (R2) was used to compare the predicted values to the observed values in the test data set. The coefficient of determination is defined as the proportion of the explained variability of the total variability53 and was used in previous studies as measure for the prediction accuracy.54,55\n\nTo perform feature selection, the variable importance of each SNP was estimated using random forest in a first step. Therefore, the R package Boruta, version 7.0.0 was used.56 The R function Boruta from this package performs multiple random forest runs with the given input data and calculates multiple quantities as the resulting variable importance per input variable. This function was used in previous studies to assess the variable importance of SNPs.54,57,58 We chose the mean variable importance as estimate of the variable importance per SNP. We used a confidence level of 10−10, 2,000 trees and 200 as the maximum number of runs.\n\nAfter the variable importance per SNP was estimated, feature selection was performed by carrying out genomic prediction with a random forest model that contained only the two SNPs with the highest variable importance. Subsequently, genomic prediction was performed using the three best SNPs, and so on. For each number of SNPs in the prediction model, the prediction accuracy as explained above was calculated. Since random forest can lead to different results in prediction accuracy even if the same data were used as training and test data set, prediction accuracy was estimated as the median prediction accuracy from ten repetitions. To prevent over-optimistic values for the prediction accuracy, variable importance was only estimated using the training data set.59 In this way, genomic prediction using feature selection can be compared to genomic prediction using all available SNPs.51,60\n\nPerforming the feature selection method as described above led to a variable importance per SNP as well as a prediction accuracy for each prediction model containing the i best SNPs for each of the ten random splits of the data set. In a next step, the prediction accuracy for each number of SNPs was defined as the median from these ten repetitions. Subsequently, the optimal number of SNPs was defined as the number of SNPs that maximised the median prediction accuracy from the ten repetitions.\n\nBesides genomic prediction with single SNPs, genomic prediction was also performed using SNP pairs. Since the genomic data set contained 9,127 SNPs after the data preparation and filtering, theoretically more than 41 million SNP pairs could be created out of these single SNPs. To reduce the resulting data set to a size that a computer can handle, PLINK’s epistasis test was performed using default settings. In this way, the interaction term of each two SNPs is tested for significance at a significance threshold of α=0.0001.61 The selection of SNP pairs was performed with each training data set individually to prevent bias during the selection process.\n\nAfter the SNP pairs were selected using PLINK’s epistasis test, the genotype of each SNP pair was defined using an additive-additive interaction model. In this way, the genotype of each SNP pair was defined as the product of both single SNPs.49 Thus, if any of the single SNPs was homozygous for the major allele (coded as 0 in the single SNPs), the genotype of the SNP pair was defined as 0. This was the case for five of the nine possible genotypes of a SNP pair. The combination of two heterozygous single SNPs would lead to a 1 for the SNP pair, the combination of a heterozygous SNP with a SNP that provides a homozygous minor allele would be 2, and the combination of two SNPs that provide homozygous minor alleles would be 4. The recoding of single SNPs as well as the resulting genotype of the SNP pair is summarised in Table 1.\n\nA and B represent major alleles and a and b represent minor alleles for SNP A and SNP B, respectively. The resulting SNP pair corresponds to the product of the single SNPs in an additive-additive SNP-interaction model.\n\nAfter the SNP pairs were recoded, genomic prediction was performed with all SNP pairs that were selected from each training data set. Therefore, a prediction model was derived using random forest with each training data set (as described above with the ranger function with default settings), the phenotypic values of the corresponding test data set were predicted with the prediction model, and prediction accuracy was estimated as R2 between the predicted and the observed values.\n\nHowever, since PLINK’s epistasis test is based on linear regression and random forest is a method from machine learning, we developed an alternative for selecting SNP pairs from single SNPs based on machine learning methods. Therefore, we used the information about the variable importance of each single SNP as it was provided by the Boruta function and combined the single SNPs with the highest variable importance to all possible SNP pairs. Subsequently, genomic prediction was performed using all SNP pairs created with the best single SNPs and the resulting prediction accuracy was stored. This process was repeated for the three to 200 single SNPs with the highest variable importance. Finally, the number of single SNPs was determined where the resulting SNP pairs maximised the prediction accuracy. As with the other methods, this method was repeated with each training data set individually to avoid bias and afterwards the median from the ten repetitions was calculated for each number of analysed SNPs. An R script as well as the data from this trial are provided at https://github.com/tmlange/IFS\\_SNPpairs.git43 to give researchers the possibility to perform feature selection with SNP pairs based on the variable importance of single SNPs.\n\n\nResults\n\nThe 155 genotypes which carry both known resistances provided raw OD values measured after 90 minutes in the range from 0.1107 to 4 which is the technical limit of the machine. The transformed data were in the range from -7.06 to 12.33. These results show the highest possible variation of virus concentrations that the machine can measure. Thus, although these genotypes were assumed to be resistant at the two known resistance clusters, the resulting data set provides sufficient variance of the resistance levels to perform genomic prediction.\n\nFirst, genomic prediction was performed using all 9,127 single SNPs that were left after filtering. Performing genomic prediction with the single SNPs with the ten random splits of the data set resulted in a median prediction accuracy of R2=0.146. The median prediction accuracies resulting from genomic prediction using any of the methods described can be seen in Table 2.\n\nNext to genomic prediction with all SNPs that were left after filtering, incremental feature selection was performed to optimise prediction accuracy by selecting a subset of optimal SNPs for genomic prediction. Therefore, Boruta was performed to estimate the variable importance of each SNP. To prevent bias in the data analysis, this analysis was performed in each training data set individually. Subsequently, genomic prediction was performed using random forest.\n\nAfter performing this analysis, each number of SNPs and the corresponding prediction accuracy was retrieved for each of the ten splits between training and test data set. Figure 1 shows the number of SNPs in the prediction model on the X axis and the corresponding prediction accuracy as the median of the prediction accuracy from the ten repetitions on the Y axis. One can see that the prediction accuracy increases steeply when the first SNPs are included in the prediction model. However, slightly above R2=0.25, the prediction accuracy forms a peak and decreases from there on with the decrease being less steep than the increase at the beginning of the curve.\n\nIn this way, the optimal set of SNPs for genomic prediction was determined. Thus, the number of SNPs was selected that maximised the median of the prediction accuracy from the ten repetitions. Here, the prediction accuracy maximised if 29 SNPs were included in the prediction model. This resulted in a median prediction accuracy of R2=0.267. However, we found that within the ten training data sets, not all 29 SNPs were the same.\n\nBesides genomic prediction and feature selection with single SNPs, similar approaches have been performed using SNP pairs. To perform genomic prediction with SNP pairs, PLINK’s epistasis test was performed with default settings for each training data set individually. After filtering via PLINK’s epistasis test, only SNP pairs were kept in the data set whose interaction term in a linear regression model led to a p value below the default threshold of 0.0001. The resulting sample sizes resulted in 46,556 to 87,529 SNP pairs. Taking the 41 million theoretically possible SNP pairs into consideration, this is a reduction to 0.1% to 0.2%. When genomic prediction was performed with all SNP pairs that were left after filtering using PLINK’s epistasis test with each training set, the median prediction accuracy was R2=0.191.\n\nBesides genomic prediction with all SNP pairs that were left after filtering with PLINK’s epistasis test, feature selection was performed to analyse an optimal subset of SNP pairs for genomic prediction. Therefore, the best single SNPs judged by their variable importance were selected and used to create SNP pairs as described in Table 1. Subsequently, genomic prediction was performed using random forest with the SNP pairs that resulted from the 3, …, 200 best single SNPs. Figure 2 displays the median prediction accuracy from the ten repetitions on the Y axis and the corresponding number of single SNPs that make up the SNP pairs on the X axis.\n\nOne can see that the prediction accuracy increases steeply when a small number of SNP pairs are included in the prediction model. Similar to Figure 1 that displays the prediction accuracy with the single SNPs, the prediction accuracy with the SNP pairs also forms a peak and decreases from there on. One can see that the peak height is slightly above R2=0.3 when SNP pairs are created using the 16 best SNPs.\n\nConsidering Figure 2, one can assume that the number of SNP pairs has an effect on the resulting prediction accuracy. Thus, one could assume that the prediction accuracy could be affected by the number of SNP pairs that is selected via PLINK’s epistasis test. Therefore, we have analysed how many SNP pairs were selected via PLINK if the significance threshold was modified. Naturally, the number of selected SNP pairs was reduced if the threshold was decreased and conversely, more SNP pairs were left after filtering if the threshold was increased. However, if subsequently all selected SNP pairs were used for genomic prediction, the resulting prediction accuracy did not seem to be affected (tested for thresholds 10−2, …, 10−8, data not shown). Thus, we conclude that although the number of selected SNP pairs can be easily adjusted in PLINK’s epistasis test, this selection did not affect the resulting prediction accuracy for this data set.\n\n\nDiscussion\n\nAlthough rhizomania resistance was assumed to be a quantitative trait caused by major and minor resistance genes,18 to date no attempt of genomic prediction of rhizomania resistance has been performed. We provide a first attempt at predicting the resistance of sugar beet genotypes against rhizomania. To do so, we used a sugar beet population where each genotpye can be assumed to be resistant at Rz1. Furthermore, 155 of the 156 genotypes can be assumed to be resistant at Rz2. Thus, all SNPs in high linkage disequilibrium with either Rz1 or Rz2 should have been removed during SNP pruning. However, the results show that genomic prediction of rhizomania resistance was still possible. In this way, we provide evidence that the genomic architecture of rhizomania resistance is most probably caused by more than two resistance clusters.\n\nTo perform genomic prediction, we split the data set ten times randomly into subsets of 80% training data and 20% test data. Performing genomic prediction with all available SNP markers led to a median prediction accuracy of R2=0.146. Moreover, we performed feature selection using methods from machine learning to reduce the number of SNPs in the prediction model to an optimal subset. This method led to a median prediction accuracy of R2=0.267 when only the 29 best SNPs were included in the prediction model.\n\nPrevious studies of variable importance in genomic prediction have concluded that although SNP interactions can be detected in random forest algorithms, such interactions can be masked by other variables when working with high-dimensional data.62,63 Thus, it could be assumed that SNP interactions are masked when genomic prediction was performed with all single SNPs. Consequently, when the number of SNPs was reduced, SNP interactions were not masked and could be included in the prediction model more efficiently.\n\nBesides genomic prediction using single SNPs, we also present results from genomic prediction using SNP pairs. For this, single SNPs were combined to pairs and the theoretical number of resulting SNP pairs was reduced using PLINK’s epistasis test. Performing genomic prediction with all SNP pairs that were left after filtering resulted in a median prediction accuracy of R2=0.191.\n\nFinally, we used the information about variable importance of each SNP to perform feature selection also with the SNP pairs. Therefore, SNP pairs were created using only the 3, …, 200 single SNPs with the highest variable importance and the corresponding prediction accuracy was estimated. This new approach allowed us to perform incremental feature selection using machine learning with SNP pairs. Similar to feature selection with single SNPs, the prediction accuracy for the SNP pairs was maximised if only a certain number of SNP pairs was included in the prediction model. Here, the prediction accuracy was maximised if the prediction model contained SNP pairs from the 16 best single SNPs. This method led to a median prediction accuracy of R2=0.306 which was the highest prediction accuracy from all four methods under investigation. These results might indicate that rhizomania is affected by interactions between SNP pairs which are also masked if all SNP pairs are included in the prediction model. Consequently, it might be assumed that not only epistatic effects caused by two genes but also by multiple genes could play a role in rhizomania resistance.\n\nFeature selection was used in recent studies to increase the prediction accuracy of genomic prediction models in man59 and crops.51,54 However, these studies led to heterogeneous results such that no general recommendation can be given regarding feature selection. Here, we show that in case of rhizomania resistance, prediction accuracy could be increased using feature selection. We postulate that the success of implementing feature selection to improve prediction accuracy might be related to epistatic effects that are masked if a large number of SNPs are included in a prediction model. However, we assume the present study alone is not sufficient to underpin this hypothesis. Thus, further research is necessary to study the role of SNP interactions in rhizomania resistance as well as the possibility to improve genomic prediction via feature selection.\n\nBesides improving prediction accuracy of genomic prediction models, other studies used results from feature selection via genomic prediction to determine the association between certain SNPs and the phenotype.54,64 Following this approach, it could be interesting to use the method presented here to select the 29 single SNPs or the 16 SNP pairs, respectively, as being associated with rhizomania resistance. However, we found that the estimation of variable importance did not lead to the same results in each training data set. Consequently, the SNP pairs differed for each training data set as well. Thus, we conclude that the present method can be useful to increase the prediction accuracy of prediction models but is not useful to select certain SNPs or SNP pairs as being associated with the phenotype.\n\n\nConclusions\n\nHere, we present a first attempt at genomic prediction of rhizomania resistance in sugar beet. Therefore, we used a sugar beet population with 156 genotypes of which all genotypes can be assumed to be resistant at Rz1 and 155 genotypes can be assumed to be resistant at Rz2. The 155 genotypes that were resistant at Rz2, provided the highest possible variation of virus concentrations that the machine can measure. Moreover, although SNPs in high linkage disequilibrium with Rz1 and Rz2 were removed during SNP pruning, genomic prediction was possible with the genomic data. If rhizomania resistance was caused only by the two known resistance clusters, this should not be the case.\n\nTo perform genomic prediction, we have used single SNPs as well as SNP pairs. In the provided data set, the genomic prediction using SNP pairs led to higher prediction accuracy than the genomic prediction using single SNPs. These results lead to the conclusion that epistatic effects might affect rhizomania resistance and that the usage of SNP pairs can include these effects more efficiently in the prediction model.\n\nMoreover, we have shown that a selection of the “best” SNPs increased prediction accuracy even further. It was concluded in former studies that although random forest can detect SNP interactions, such interactions can be masked by other variables in high-dimensional data.62,63 In this way, our results fit to the conclusions from these studies since the prediction accuracy was increased if only a subset of all available SNPs was used for genomic prediction. Moreover, our results indicate that the variable importance that was estimated using Boruta, hence, random forest, also included information about SNP interactions. Thus, we conclude that a reduction of the SNP number via the variable importance enables the random forest algorithm to incorporate SNP interactions better into the prediction model.\n\nFurthermore, we have also performed feature selection with the SNP pairs to reduce the data set to a certain subset of optimal SNP pairs. The inclusion of a subset of SNP pairs in the prediction model increased the prediction accuracy compared to the prediction model that included all SNP pairs that were left after filtering via PLINK’s epistasis test. Following the conclusion with the single SNPs, this might indicate that rhizomania resistance is caused by interactions of more than two genes and that the interaction of SNP pairs might be similarly masked if a large number of SNP pairs is included in the prediction model.\n\nAll in all, the optimisation of the prediction model increased the median prediction accuracy with the ten repetitions that are provided here. These results make us assume that rhizomania resistance could be caused by a multitude of genes which interact and that the implementation of such interactions in a prediction model can increase prediction accuracy. However, further research in this regard is necessary. To encourage researchers to perform feature selection with SNP pairs in their own studies, we have published an R script as well as the data from this trial at https://github.com/tmlange/IFS_SNPpairs.git.43",
"appendix": "Data availability\n\nZenodo: IFS_SNPpairs v1.0, https://doi.org/10.5281/zenodo.7624425. 43\n\nThis project contains the following underlying data:\n\n• TestData.csv\n\n• TrainingData.csv\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nAnalysis code\n\nAnalysis code available from: https://github.com/tmlange/IFS_SNPpairs.git\n\nArchived analysis code at time of publication: https://doi.org/10.5281/zenodo.7624425. 43\n\nLicense: MIT\n\n\nAcknowledgements\n\nWe acknowledge support by the Open Access Publication Funds of the Göttingen University. Furthermore, we would like to thank the Phytopathology group of KWS SAAT SE & Co. KGaA for performing the greenhouse trial and laboratory work.\n\n\nReferences\n\nŘezbová H, Belová A, Škubna O: Sugar beet production in the European Union and their future trends. 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Secretariat General. 1987.\n\nStevanato P, De Biaggi M, Broccanello C, et al.: Molecular genotyping of “rizor” and “holly” rhizomania resistances in sugar beet. Euphytica. 2015; 206(2): 427–431. Publisher Full Text\n\nScholten OE, De Bock TSM, Klein-Lankhorst RM, et al.: Inheritance of resistance to beet necrotic yellow vein virus in Beta vulgaris conferred by a second gene for resistance. Theor. Appl. Genet. 1999; 99(3-4): 740–746. PubMed Abstract | Publisher Full Text\n\nCapistrano-Gossmann GG, Ries D, Holtgräwe D, et al.: Crop wild relative populations of Beta vulgaris allow direct mapping of agronomically important genes. Nat. Commun. 2017; 8(1): 1–8.\n\nGidner S, Lennefors B-L, Nilsson N-O, et al.: QTL mapping of BNYVV resistance from the WB41 source in sugar beet. Genome. 2005; 48(2): 279–285. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nCordell HJ: Epistasis: what it means, what it doesn’t mean, and statistical methods to detect it in humans. Hum. Mol. Genet. 2002; 11(20): 2463–2468. PubMed Abstract | Publisher Full Text\n\nMathew B, Léon J, Sannemann W, et al.: Detection of epistasis for flowering time using bayesian multilocus estimation in a barley MAGIC population. Genetics. 2018; 208(2): 525–536. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCarlborg Ö, Haley CS: Epistasis: too often neglected in complex trait studies?. Nat. Rev. Genet. 2004; 5(8): 618–625. PubMed Abstract | Publisher Full Text\n\nHeinrich F, Ramzan F, Rajavel A, et al.: MIDESP: Mutual Information-Based Detection of Epistatic SNP Pairs for Qualitative and Quantitative Phenotypes. Biology. 2021; 10(9): 921. 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Breed. 2018; 38(5): 1–16. Publisher Full Text\n\nRoy J, Shaikh TM, del Río Mendoza L , et al.: Genome-wide association mapping and genomic prediction for adult stage sclerotinia stem rot resistance in brassica napus (l) under field environments. Sci. Rep. 2021; 11(1): 1–18. Publisher Full Text\n\nHuang M, Balimponya EG, Mgonja EM, et al.: Use of genomic selection in breeding rice (Oryza sativa L.) for resistance to rice blast (magnaporthe oryzae). Mol. Breed. 2019; 39(8): 1–16. Publisher Full Text\n\nTomar V, Singh Dhillon G, Singh D, et al.: Evaluations of genomic prediction and identification of new loci for resistance to stripe rust disease in wheat (Triticum aestivum L.). Front. Genet. 2021; 12. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOrnella L, Pérez P, Tapia E, et al.: Genomic-enabled prediction with classification algorithms. Heredity. 2014; 112(6): 616–626. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGonzález-Camacho JM, Ornella L, Pérez-Rodríguez P, et al.: Applications of machine learning methods to genomic selection in breeding wheat for rust resistance. Plant Genome. 2018; 11(2): 170104. PubMed Abstract | Publisher Full Text\n\nLange TM: IFS_SNPpairs.Feb 2023. Reference Source\n\nSchirmer A, Link D, Cognat V, et al.: Phylogenetic analysis of isolates of Beet necrotic yellow vein virus collected worldwide. J. Gen. Virol. 2005; 86(10): 2897–2911. PubMed Abstract | Publisher Full Text\n\nLange TM, Wutke M, Bertram L, et al.: Decision Strategies for Absorbance Readings from an Enzyme-Linked Immunosorbent Assay—A Case Study about Testing Genotypes of Sugar Beet (Beta vulgaris L.) for Resistance against Beet necrotic yellow vein virus (BNYVV). Agriculture. 2021; 11(10): 956. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nAzodi CB, Bolger E, McCarren A, et al.: Benchmarking parametric and machine learning models for genomic prediction of complex traits. G3: Genes, Genomes, Genetics. 2019; 9(11): 3691–3702. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWright MN, Ziegler A: ranger: A fast implementation of random forests for high dimensional data in C++ and R. J. Stat. Softw. 2017; 77(1): 1–17. Publisher Full Text\n\nRenaud O, Victoria-Feser M-P: A robust coefficient of determination for regression. J. Stat. Plan. Inference. 2010; 140(7): 1852–1862. Publisher Full Text\n\nHaleem A, Klees S, Schmitt AO, et al.: Deciphering pleiotropic signatures of regulatory SNPs in Zea mays L. using multi-omics data and machine learning algorithms. Int. J. Mol. Sci. 2022; 23(9): 5121. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSegelke D, Chen J, Liu Z, et al.: Reliability of genomic prediction for German Holsteins using imputed genotypes from low-density chips. J. Dairy Sci. 2012; 95(9): 5403–5411. PubMed Abstract | Publisher Full Text\n\nKursa MB, Rudnicki WR: Feature selection with the Boruta package. J. Stat. Softw. 2010; 36: 1–13. Publisher Full Text\n\nRamzan F, Klees S, Schmitt AO, et al.: Identification of Age-Specific and Common Key Regulatory Mechanisms Governing Eggshell Strength in Chicken using Random Forests. Gen. 2020; 11(4): 464. Publisher Full Text\n\nKlees S, Lange TM, Bertram H, et al.: In silico identification of the complex interplay between regulatory snps, transcription factors, and their related genes in brassica napus l. using multi-omics data. Int. J. Mol. Sci. 2021; 22(2): 789. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBermingham ML, Pong-Wong R, Spiliopoulou A, et al.: Application of high-dimensional feature selection: evaluation for genomic prediction in man. Sci. Rep. 2015; 5(1): 1–12.\n\nSirsat MS, Oblessuc PR, Ramiro RS: Genomic prediction of wheat grain yield using machine learning. Agriculture. 2022; 12(9): 1406. Publisher Full Text\n\nChang C: Epistasis test - plink 1.9. Retrieved March 01, 2022, 2022. Reference Source\n\nWinham SJ, Colby CL, Freimuth RR, et al.: SNP interaction detection with random forests in high-dimensional genetic data. BMC bioinformatics. 2012; 13(1): 1–13. Publisher Full Text\n\nWright MN, Ziegler A, König IR: Do little interactions get lost in dark random forests? BMC bioinformatics. 2016; 17(1): 1–10. Publisher Full Text\n\nShikha M, Kanika A, Rao AR, et al.: Genomic selection for drought tolerance using genome-wide snps in maize. Front. Plant Sci. 2017; 8: 550. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "181537",
"date": "28 Jul 2023",
"name": "J Mitchell McGrath",
"expertise": [
"Reviewer Expertise Genetics",
"genomics",
"and germplasm enhancement of sugar beet"
],
"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\nFirst review of draft of \"Improving genomic prediction of rhizomania resistance in sugar beet (Beta vulgaris L.) by implementing epistatic effects and feature selection.\" by Lange et al. (doi.org/10.12688/f1000research.131134.1) for potential indexing.\nThis manuscript details computational investigations using genomic prediction methods to evaluate rhizomania resistance in sugar beet. The topic is very important and results would be useful for sugar beet breeders, and other scientists interested in genomic prediction for their traits of interest. The approach taken is valid, and the authors are highly regarded with good facilities and means to accomplish their task. The authors appear to have generated some evidence suggesting additional factors beyond the traditional single gene rhizomania resistances may be available for breeding enhancement for rhizomania resistance, however, the manuscript needs revision to make this clearer and marginally useful.\nIt seems that a study to dissect additional components of rhizomania resistance would include analysis of the rhizomania resistance genes. The authors state that the germplasm used were 'assumed' to carry the relevant genes Rz1 and Rz2 (in all but one of 156 entries) (gene symbols need to be italicized in publication). It is entirely unclear what material was used (presumably material initiating from KWS), with one statement suggesting 156 lines and, conversely, a following statement that two lines were crossed and selfed for two generations. Which of these are the population(s) for which the analyses were done? And if both, it needs to be made clearer in the text, as well as for what question each of the populations was used. A list of germplasm used should be included.\nAnalyses proceeded without using SNPs for the two named resistance genes, and I think this is a flaw in the logic of the paper. Evidence for the assumption that the germplasm is resistant is essential. Assuming the author's assumption is valid, the logic for excluding SNPs for Rz1 and Rz2 should be presented. I suspect there may have been a concern that the known genes with major effect may have overwhelmed the signal from discovered modifiers (the point of the manuscript), however this needs to be demonstrated. If this is the case, what are the implications for the 'strength' or 'effectiveness' of the discovered modifiers? Since the manuscript deals strictly with in silico investigations, it seems a relatively small matter to test the effect of named resistance genes on the results, and then exclude for cause if that is indeed the case.\nThe author's writing suggests many assumptions were used in their analyses. It is difficult to interpret what is indeed a true assumption from a postulate they wish to have tested, so purging the manuscript for words relating to 'assume' would create better credibility for the work, unless it is absolutely essential (and even then with clear implication for their results if the assumption does not hold). (For many assumptions presented, relatively simple procedures can validate them, which may have been done in the course of the work.) Excluding SNPs with a major allele frequency of >0.95 seems arbitrary as well, although as above, it is difficult to ascertain the author's intent given the questions of the population(s) evaluated. So, in that respect, the manuscript can not be properly vetted yet.\nAs suggestions for revision, clarity of writing for an audience is essential. Right now, this seems to be a draft that organizes the authors' thoughts into a manuscript format. Jargon should be avoided. Assumptions should be justified. Where available, actual numbers should be presented (rather than qualitative statements such as 'many', 'the remaining', etc.) to allow the reader to properly account for the process obtaining results. Concepts used should be defined (e.g. 'variable importance', 'technical limit', etc.). I would also like to see what genomic regions the author's have discovered and how the different methods/ algorithms differed with respect to the types of genes and elements discovered. Specifically, one needs evidence that this approach is likely to be successful. Or, if this is a manuscript describing negative results, that should be stated as well.\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? 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": "12252",
"date": "28 Aug 2024",
"name": "Thomas Martin Lange",
"role": "Author Response",
"response": "Reviewer Comment: (1) It seems that a study to dissect additional components of rhizomania resistance would include analysis of the rhizomania resistance genes. The authors state that the germplasm used were 'assumed' to carry the relevant genes Rz1 and Rz2 (in all but one of 156 entries) (gene symbols need to be italicized in publication). It is entirely unclear what material was used (presumably material initiating from KWS), with one statement suggesting 156 lines and, conversely, a following statement that two lines were crossed and selfed for two generations. Which of these are the population(s) for which the analyses were done? And if both, it needs to be made clearer in the text, as well as for what question each of the populations was used. A list of germplasm used should be included. Author Response: After revising the addressed paragraph, we agree with the reviewer's assessment. The paragraph describing the experimental design and, notably, the composition of the analysed population was overly complex and did not clearly articulate how the population was established. We have revised the paragraph to provide a clearer explanation of the population's creation and genotyping process. Additionally, the reviewer raised concerns regarding the lack of naming for the initial two sugar beet lines used to create this population. We acknowledge that the rights to the germplasm utilised in this trial are held by KWS Saat SE & Co. KGaA, and as such, we are unable to disclose this information. However, in response to the reviewer's criticism, we have included a data availability statement in the manuscript and italicised the gene names. Reviewer Comment: (2) Analyses proceeded without using SNPs for the two named resistance genes, and I think this is a flaw in the logic of the paper. Evidence for the assumption that the germplasm is resistant is essential. Assuming the author's assumption is valid, the logic for excluding SNPs for Rz1 and Rz2 should be presented. I suspect there may have been a concern that the known genes with major effect may have overwhelmed the signal from discovered modifiers (the point of the manuscript), however this needs to be demonstrated. If this is the case, what are the implications for the 'strength' or 'effectiveness' of the discovered modifiers? Since the manuscript deals strictly with in silico investigations, it seems a relatively small matter to test the effect of named resistance genes on the results, and then exclude for cause if that is indeed the case. Author Response: We appreciate the reviewer's point regarding the importance of providing evidence for the assumption of germplasm resistance. Indeed, we have conducted an analysis of the resistance of the population at Rz1 and Rz2 using SNP markers. However, it is crucial to note that the SNPs in high linkage disequilibrium (LD) with Rz1 and Rz2 exhibit minimal genetic variance because all plants in the population are resistant at the two known resistance genes. Consequently, these SNPs do not contribute any meaningful information and are unsuitable for genomic prediction. Consequently, these SNPs were removed due to minor allele frequency filtering (MAF smaller than or equal to 0.05). We recognise that the omission of this information about the removal of SNPs in high LD with the resistance genes may has caused confusion, and we have thoroughly adjusted the Materials and Methods section of the manuscript to clarify this aspect. Reviewer Comment: (3) The author's writing suggests many assumptions were used in their analyses. It is difficult to interpret what is indeed a true assumption from a postulate they wish to have tested, so purging the manuscript for words relating to 'assume' would create better credibility for the work, unless it is absolutely essential (and even then with clear implication for their results if the assumption does not hold). (For many assumptions presented, relatively simple procedures can validate them, which may have been done in the course of the work.) Excluding SNPs with a major allele frequency of >0.95 seems arbitrary as well, although as above, it is difficult to ascertain the author's intent given the questions of the population(s) evaluated. So, in that respect, the manuscript can not be properly vetted yet. Author Response: We acknowledge the reviewer's feedback and have revised the manuscript accordingly. We acknowledge that the term \"to assume\" was overused, particularly when describing the \"assumption\" that the plants are resistant at Rz1 and Rz2. As detailed in the manuscript, the plants were analysed using SNP markers. All genotypes were homozygous for the resistance gene at SNPs in high LD with Rz1, and 155 out of 156 genotypes were homozygous for the resistance gene at SNPs in high LD with Rz2. However, we use the term \"to assume\" because LD does not provide absolute certainty that an individual carries the specified gene when the corresponding SNP marker shows a particular allele. Nonetheless, the reviewer's point is well taken, and we have adjusted the relevant sections to enhance the manuscript's readability. Furthermore, the reviewer criticised the removal of SNPs with a major allele frequency of 0.95 or higher from the data set. This practice is common to ensure that each SNP contributes sufficient genetic variance in both the training and test populations. Therefore, we do not intend to alter this aspect of the method or the corresponding section of the manuscript. Reviewer Comment: (4) As suggestions for revision, clarity of writing for an audience is essential. Right now, this seems to be a draft that organizes the authors' thoughts into a manuscript format. Jargon should be avoided. Assumptions should be justified. Where available, actual numbers should be presented (rather than qualitative statements such as 'many', 'the remaining', etc.) to allow the reader to properly account for the process obtaining results. Concepts used should be defined (e.g. 'variable importance', 'technical limit', etc.). I would also like to see what genomic regions the author's have discovered and how the different methods/ algorithms differed with respect to the types of genes and elements discovered. Specifically, one needs evidence that this approach is likely to be successful. Or, if this is a manuscript describing negative results, that should be stated as well. Author Response: We appreciate the reviewer's feedback and agree that the writing style of the manuscript required improvement. We have revised the manuscript accordingly. Definitions of technical terms, such as variable importance and the technical limit of the machine, have been added for clarity. Additionally, we have included more information on the overlap in methods regarding the detection of important SNPs. In response to the reviewer's criticism, KWS Saat SE & Co. KGaA agreed to publish the chromosomes on which SNPs are located that were detected using our method. We have also added a data availability statement to the manuscript stating that the exact position on the chromosome as well as the genomic positions of the other SNPs in this data set are available upon reasonable request."
}
]
},
{
"id": "201121",
"date": "12 Sep 2023",
"name": "Muhammad Massub Tehseen",
"expertise": [
"Reviewer Expertise Sugarbeet genetics",
"genomics and breeding."
],
"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 paper aimed at comparing several four methods to investigate genomic prediction models to predict rhizomnia resistance in sugar beet. The topic is of general interest and the findings could be used in sugar beet breeding programs targeting rhizomnia resistance. However, there were certain limitations in the manuscript like insufficient description of Materials and methods, phenoytpic data not reliable, lacking novelty. The manuscript needs to be substantially revised to be able to be indexed.\nFirst of all there is no clear description of the population panel used in the current study, the authors reported a panel of 156 genotypes followed by a cross and the progenies were advanced for two generations. It is very unclear as for what is happening, whether the 156 initial were used or the progenies derived from the cross? Why the crosses were made? The choice of parents and the reason or basis of selection? The authors assume the presence/absence of resistance which is not backed up by the variance in the phenotypic data generated. There should be detail description of the panel used, the experimental design, replications and phenotypic data generation.\nThe genomic prediction (GP) for any trait relies heavily on the traits heritability values, here the authors have claimed the maximum GP estimates of .030 which is fairly below moderate however it is hard to conclude its reliability without judging the quality and heritability values of the traits under study. Therefore, authors’ are suggested to estimate heritability before reporting any conclusions.\nThe analysis was conducted without including SNP in LD with the two resistance genes which seems to be strange and requires clarification from authors as why it was done? If the presence of highly associated SNPs would skew the prediction results then they should be mentioned and in fact presented side by side for comparison. Furthermore, to avoid the prediction ability influence by the low number of cross-validation i.e. 5-fold in the current study, each method should have run at least 100 CVs. If not 50 instead of just 10. The 10 times iteration generally just gives a rough idea of the prediction accuracy for more reliable estimates there should be at least 50 iterations.\nAs for the revision of the manuscript, the authors should avoid the lots of repetition and use of assumptions in the text. In many instances the assumed statements could be verified easily. The authors are requested to re-submit the revised manuscript to be considered for indexing.\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? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12253",
"date": "28 Aug 2024",
"name": "Thomas Martin Lange",
"role": "Author Response",
"response": "Reviewer Comments: (1) First of all there is no clear description of the population panel used in the current study, the authors reported a panel of 156 genotypes followed by a cross and the progenies were advanced for two generations. It is very unclear as for what is happening, whether the 156 initial were used or the progenies derived from the cross? Why the crosses were made? The choice of parents and the reason or basis of selection? The authors assume the presence/absence of resistance which is not backed up by the variance in the phenotypic data generated. There should be detail description of the panel used, the experimental design, replications and phenotypic data generation. Author Response: We agree with the reviewer that the manuscript did not provide sufficient detail on how the sugar beet population in this trial was created. We have revised the corresponding paragraph to improve the clarity of the study. Reviewer Comments: (2) The genomic prediction (GP) for any trait relies heavily on the traits heritability values, here the authors have claimed the maximum GP estimates of .030 which is fairly below moderate however it is hard to conclude its reliability without judging the quality and heritability values of the traits under study. Therefore, authors’ are suggested to estimate heritability before reporting any conclusions. Author Response: It is important to clarify that our analysis focuses on the coefficient of determination (R2) rather than the correlation coefficient (r). R2 is generally lower than r and represents the proportion of the variance explained by the model. In this context, the GP estimate of 0.30 suggests that a significant portion of the trait's variance can be explained by genomic information, demonstrating the potential of genomic prediction for this particular trait. We agree that heritability estimates are crucial for assessing the reliability of GP and acknowledge the need to consider the quality and heritability values of the traits under study. Therefore, we concur with the reviewer's recommendation to include heritability estimates in future studies which would provide a more comprehensive understanding of the trait's predictability. In the current manuscript, our primary objective was to demonstrate the feasibility of genomic prediction for this trait, even with lower GP estimates. We believe that our results demonstrate potential in this area and we look forward to refining our analysis by incorporating heritability estimates in future research to strengthen our conclusions. Reviewer Comments: (3) The analysis was conducted without including SNP in LD with the two resistance genes which seems to be strange and requires clarification from authors as why it was done? If the presence of highly associated SNPs would skew the prediction results then they should be mentioned and in fact presented side by side for comparison. Furthermore, to avoid the prediction ability influence by the low number of cross-validation i.e. 5-fold in the current study, each method should have run at least 100 CVs. If not 50 instead of just 10. The 10 times iteration generally just gives a rough idea of the prediction accuracy for more reliable estimates there should be at least 50 iterations. Author Response: As thoroughly explained in the manuscript, each individual in the population is resistant at Rz1, with only one individual being susceptible at Rz2. The SNPs in high LD with the known resistance genes were not removed to skew prediction results. Instead, SNPs in high LD with Rz1 provide no variance and, thus, carry no useful information. The same applies to SNPs in high LD with Rz2, as they are identical for all but one individual in the population. Therefore, these SNPs were excluded in the minor allele frequency filtering step (MAF smaller than or equal to 0.05) which is standard practice to ensure minimum genetic variance in both the test and training data sets. Regarding the second part of the criticism, the methods we used are computationally intensive, making it impractical to repeat the analysis 100 times as suggested. We employed a ten-fold repetition, consistent with similar research methodologies. For instance, Azodi et al. (2019) utilised this number of repetitions in their study on benchmarking parametric and machine learning models for genomic prediction of complex traits. As stated in the manuscript, our R script and data are publicly available and we encourage the reviewer or any interested party to replicate the study with a higher number of repetitions if desired. Reviewer Comments: (4) As for the revision of the manuscript, the authors should avoid the lots of repetition and use of assumptions in the text. In many instances the assumed statements could be verified easily. The authors are requested to re-submit the revised manuscript to be considered for indexing. Author Response: We appreciate the reviewer's criticism and agree that the manuscript's writing style required enhancement. We have revised the manuscript to improve the writing style, addressing the reviewer's concerns by reducing repetitions and clarifying assumptions."
}
]
},
{
"id": "196899",
"date": "27 Sep 2023",
"name": "Daniela Holtgräwe",
"expertise": [
"Reviewer Expertise Plant genetics",
"crop genomics",
"computational biology",
"transcriptomics",
"genome assembly",
"gene annotation",
"RGAs",
"genetic mapping",
"genotyping"
],
"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 present manuscript deals with genomic prediction of the presumably quantitative trait 'Rhizomania resistance' in sugar beet using genome-wide SNP data. The paper presents bioinformatic and ML-based calculations using all SNPs individually, or in pairs and adding the SNP information step by step. The pyramiding of sugar beet resistance to rhizomania is of great interest from an agronomic and breeding perspective and is very challenging due to the concentration of the loci on a single chromosome (chr. 3). Medium and large SNP genotyping data sets, such as those used here, are generally well suited for improved prediction of a trait, especially if several genes or gene clusters are involved in the expression of the trait. Not only the aim of the investigations, but also the selection of the sugar beet population and the various bioinformatic methods are interesting and well designed. Nevertheless, the manuscript must be revised with regard to the transparency of the biological material, the data used and the limitations of the results. The revision should present the data in a way so that the results and experiences become more usable for those interested.\nMain points:\nIn the introduction, the individual genes identified to confer resistance to Rhizomania should be mentioned and the underlying resistance mechanism, if known, should be briefly described. At least Rz2 is well studied in this regard. Two clusters are believed to exist on chr. 3. Associated genomic markers are known for each Rz locus, so that the physical distance of these genes can be specified on a reference sequence in addition to genetic distance in cM. Furthermore, it is not clear why the authors assume epistasis rather than additive effects between the genes involved.\n\nThe description of the sugar beet population employed is incomplete. As a result, it is unclear which genetic material was used. A look at the authors list allows to speculate about the sugar beet genotype used for generating the population (Liebe et al., 2023; Wetzel et al., 2021). However, unequivocal specification of the material used is mandatory.\n\nFor the DAS-ELISA description the range of OD-values is missing. OD measurements were done 30, 60, and 90 minutes, but only data for the 90 min time point are provided. The authors should leave a comment, why they focused on the data obtained after 90 min of antibody exposure.\n\nFurther, it is unclear from which experimental approach the SNP data were derived. Do the authors really mean SNP or SNVs? Where do missing values come from? What is the overall SNP frequency? These questions are also points that need to be taken up in the discussion.\n\nThe programs on github look very useful, but the data from the trial are not easily accessible due to limited documentation. Therefore, the documentation needs to be improved significantly.\n\nIn the methods section, is one of 155 and not of 156 genotypes susceptible to Rz2? Is this a typo?\n\nIt would be easier to track the genotype, if the authors would provide a population name and a number or name for each individual in this population.\n\nFor the feature selection “125 data points” were chosen for training data. These section needs to be re-phrased in order to make clear that SNP data from 125 genotypes (80% of individuals in population) at a certain recoded position was used.\n\nThe authors should discuss why they use genome wide SNP data and don't just use SNPs from chromosome 3 and therefore could require less computing power.\n\nVery interesting is that a set of 29 SNPs each seems to have the highest predictive performance. The reader could certainly make more sense out of this observation if one or two of these different sets were shown as well as the overlap between all 1-10 sets.\n\nThe second section of the discussion has a duplicated part to the results section. The same is true for the conclusion and the discussion, please rephrase and remove redundancy.\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?\nYes\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": [
{
"c_id": "12254",
"date": "28 Aug 2024",
"name": "Thomas Martin Lange",
"role": "Author Response",
"response": "Reviewer Comment: (1) In the introduction, the individual genes identified to confer resistance to Rhizomania should be mentioned and the underlying resistance mechanism, if known, should be briefly described. At least Rz2 is well studied in this regard. Two clusters are believed to exist on chr. 3. Associated genomic markers are known for each Rz locus, so that the physical distance of these genes can be specified on a reference sequence in addition to genetic distance in cM. Furthermore, it is not clear why the authors assume epistasis rather than additive effects between the genes involved. Author Response: We agree with the reviewer and have adjusted the introduction based on the recommendations of the reviewer. Furthermore, we have adjusted the Discussion section of the manuscript by adding a short discussion about epistasis and additive effects affecting rhizomania resistance. Reviewer Comment: (2) The description of the sugar beet population employed is incomplete. As a result, it is unclear which genetic material was used. A look at the authors list allows to speculate about the sugar beet genotype used for generating the population (Liebe et al., 2023; Wetzel et al., 2021). However, unequivocal specification of the material used is mandatory. Author Response: Unfortunately, the rights to the germplasm used in this trial are held by KWS Saat SE & Co. KGaA. We are therefore not in the position to publish this information. However, we have added a data availability statement to the manuscript stating that this information can be shared upon reasonable request. Reviewer Comment: (3) For the DAS-ELISA description the range of OD-values is missing. OD measurements were done 30, 60, and 90 minutes, but only data for the 90 min time point are provided. The authors should leave a comment, why they focused on the data obtained after 90 min of antibody exposure. Author Response: For the analysis, we have focused on the transformed data that were produced by transforming and averaging the ELISA measurements at all three time points. At the beginning of the results section, however, we have briefly described the OD measurements to show the range of the resulting OD values. Nevertheless, we agree with the reviewer that it is not clear why we have described the range of the OD values measured after 90 minutes and not after 60 and 120 minutes. Thus, we have added the range of the ELISA measurements after 60 and 120 minutes in the manuscript. Reviewer Comment: (4) Further, it is unclear from which experimental approach the SNP data were derived. Do the authors really mean SNP or SNVs? Where do missing values come from? What is the overall SNP frequency? These questions are also points that need to be taken up in the discussion. Author Response: We appreciate the reviewer's criticism and agree that the current version of the manuscript lacked detailed information about the SNPs. Additionally, the reviewer correctly pointed out that, prior to MAF filtering, we are actually considering SNVs, not SNPs. However, we would like to keep referring to the SNVs as SNPs to improve readability of the manuscript since the data were collected using a SNP chip. Reviewer Comment: (5) The programs on Github look very useful, but the data from the trial are not easily accessible due to limited documentation. Therefore, the documentation needs to be improved significantly. Author Response: We acknowledge the reviewer’s valuable feedback regarding the accessibility of the data from the trial on GitHub. We agree with the criticism and have significantly improved the documentation as requested. This should ensure that the data are now easily accessible and usable. Reviewer Comment: (6) In the methods section, is one of 155 and not of 156 genotypes susceptible to Rz2? Is this a typo? Author Response: This was indeed a typo and we have corrected the corresponding part of the manuscript. Reviewer Comment: (7) It would be easier to track the genotype, if the authors would provide a population name and a number or name for each individual in this population. Author Response: We have added genotype names for each individual in the data set on GitHub. Furthermore, we have given a special name for the genotype that was susceptible at Rz2 (``Control_susceptibleRz2''). Reviewer Comment: (8) For the feature selection “125 data points” were chosen for training data. These section needs to be re-phrased in order to make clear that SNP data from 125 genotypes (80% of individuals in population) at a certain recoded position was used. Author Response: We thank the reviewer for this very attentive comment and have adjusted the corresponding part of the manuscript. Reviewer Comment: (9) Very interesting is that a set of 29 SNPs each seems to have the highest predictive performance. The reader could certainly make more sense out of this observation if one or two of these different sets were shown as well as the overlap between all 1-10 sets. Author Response: Following the suggestion, we conducted an analysis to assess the overlap of the selected SNPs. Our findings revealed that four SNPs were consistently identified through this approach. Subsequently, we have integrated this information into the manuscript, highlighting that these four detected SNPs account for a significant portion of the total variance in the phenotypic data. Reviewer Comment: (10) The authors should discuss why they use genome wide SNP data and don't just use SNPs from chromosome 3 and therefore could require less computing power. Author Response: Thanks to the advice of the reviewer to analyse the overlap of selected SNPs, we discovered four SNPs that carry information about rhizomania resistance. In consultation with KWS Saat SE & Co. KGaA, we were allowed to publish the chromosomes on which these four SNPs are located. We show that two of the identified SNPs are not located on chromosome 3 but on chromosomes 2 and 5. We have included this new information in the manuscript which shows the importance of including SNPs from various chromosomes when examining SNP interactions. Reviewer Comment: (11) The second section of the discussion has a duplicated part to the results section. The same is true for the conclusion and the discussion, please rephrase and remove redundancy. Author Response: We appreciate the reviewer's feedback and acknowledge that the manuscript's writing style required enhancement. In response to the reviewer's criticism, we have refined the writing style of the manuscript to reduce redundancy in both the discussion and conclusion sections."
}
]
}
] | 1
|
https://f1000research.com/articles/12-280
|
https://f1000research.com/articles/13-260/v1
|
12 Apr 24
|
{
"type": "Research Article",
"title": "Poweromin X Ten, a polyherbal formulation improves male sexual function: In vivo and network pharmacology study",
"authors": [
"Sree Lalitha Bojja",
"Kiran Kumar Kolathur",
"Bhim Bahadur Chaudhari",
"Gangadhar Hari",
"Bharath Harohalli Byregowda",
"Sai Teja Meka",
"Esekia Raja Selvan",
"Sudheer Moorkoth",
"Nitesh Kumar",
"Anoop Austin",
"C. Mallikarjuna Rao",
"Sree Lalitha Bojja",
"Kiran Kumar Kolathur",
"Bhim Bahadur Chaudhari",
"Gangadhar Hari",
"Bharath Harohalli Byregowda",
"Sai Teja Meka",
"Esekia Raja Selvan",
"Sudheer Moorkoth",
"Nitesh Kumar"
],
"abstract": "Introduction Poweromin X Ten (PXT) is a polyherbal formulation, traditionally used to enhance male sexual function. However, the safety and benefits of PXT have not been scientifically evaluated. Therefore, the present study investigated the toxicity and aphrodisiac potential of PXT in male rats and explored its principal mechanisms of action.\n\nMethods Male Wistar rats were orally administered PXT (50 or 100 mg/kg) for 28 days, and sexual activity parameters, including latency and frequency of mounting and intromissions, were studied. The reproductive toxicity and spermatogenic potential were also examined. Furthermore, dopamine and serotonin levels in brain regions associated with sexual activity were assessed. Network analysis was used to identify the key bioactive compounds and their core targets involved in their beneficial actions.\n\nResults Treatment with PXT improved sexual activity in male rats, as evidenced by reduced mounting and intromission latency and a significant increase in mount frequency. Moreover, PXT exhibited spermatogenic potential and did not induce reproductive toxicity. Notably, treatment with 50 mg/kg PXT elevated dopamine levels in median preoptic area and hypothalamus. Pathway analysis indicated that PXT primarily modulated the PI3K-Akt, calcium, and MAPK signalling pathways to enhance male sexual function. Network analysis identified macelignan, β-estradiol, testosterone, and paniculatine as key bioactive components of PXT, which likely act through core targets, such as androgen receptor (AR), Mitogen-activated protein kinase 3 (MAPK3), epidermal growth factor receptor (EGFR), estrogen receptor 1 (ESR1), and vascular endothelial growth factor (VEGF) to facilitate the improvement of male sexual function.\n\nConclusion Study results suggest that PXT is a safer alternative with aphrodisiac and spermatogenic potential. These effects are partly attributed to the enhanced dopamine levels in the brain. Furthermore, this study provides insights into the specific signalling pathways and bioactive compounds that underlie the improvements in male sexual function associated with PXT.",
"keywords": [
"LC-MS/MS",
"Network pharmacology",
"Polypharmacology",
"Reproductive toxicity",
"Sexual activity",
"Dopamine"
],
"content": "1. Introduction\n\nSexual activity is essential for various aspects of physical and psychological health, including cardiovascular1 and immune function.2 The sexual response cycle in men comprises sexual desire, arousal, erection, and sexual activity, which, when negatively affected, can result in sexual dysfunction.3 A variety of factors, such as psychological, neurological and vascular diseases, trauma, surgery, and drugs can lead to sexual dysfunction.4 Globally, 20–30% of adult men reported having at least one major sexual disorder, and its prevalence increases with age.5 With increasing stress and anxiety, unhealthy lifestyles, pollutants, and importantly comorbidities, the prevalence of sexual disorders has rapidly increased.4\n\nAs sexual disorders continue to increase at an alarming rate, there lies a huge dearth of effective treatments. Only a few drugs exist to improve sexual behavior, one of them is sildenafil citrate, which has gained popularity for treating erectile dysfunction and also as a libido booster. However, this drug causes a number of limiting side effects such as arrhythmias, headaches, facial flushing, blurred vision, and mental confusion.6 In such instances, traditional medicine offers several plant-based drugs, such as Safed Musli, Ashwagandha, Gokshur, etc. which have been safely used as aphrodisiacs for ages. These plants are reported to contain bioactive compounds, such as saponins, flavonoids, phenols, alkaloids, and volatile oils, which might improve sexual behavior and treat sexual disorders.7\n\nPoweromin X Ten (PXT) is a marketed polyherbal formulation used to improve male sexual function in healthy populations. It is composed of extracts from medicinal plants of aphrodisiac value, including Tribulus terrestris fruit,8 Withania somnifera root,9,10 Asparagus racemosus root,11,12 Punica granatum seed,13,14 Myristica fragrans mace,15 Chlorophytum arundinaceum root,6 Cuculigo orchoides rhizome,16 Celastrus paniculatus seed, Orchis mascula root, and Shilajit exudate,17 at a standard ratio. However, the safety and beneficial claims of PXT have not yet been scientifically evaluated. Furthermore, the principal phytoconstituents and mechanisms through which they improve male sexual function remain unknown. Therefore, the current study aimed to investigate the safety and efficacy of the PXT formulation in male Wistar rats. In addition, the mechanisms and key targets of PXT in male sexual function were identified using a network pharmacology approach.\n\n\n2. Methods\n\nThe study protocol was approved by the Institutional Animal Ethics Committee (IAEC/KMC/50/2022 dated 26.03.2022), Manipal Academy of Higher Education (MAHE), and the experiments were carried out at the Central Animal Research Facility (CARF), Manipal, Karnataka, India (CPCSEA Reg no. 94/Po/ReBi/S/1999/CPCSEA). Male Wistar rats (180–200 g) bred at the CARF, MAHE, Manipal, were procured for this study. Rats were housed two per cage in polypropylene cages and maintained under standard laboratory conditions, 22 ± 2° C, RH 55-70% with 12 h light and dark cycle as per CCSEA (Committee for Control and Supervision of Experiments on Animal) guidelines. Rats were fed a standard pellet diet and water ad libitum. The study was conducted according to ARRIVE guidelines 2.0, using the ARRIVE Essential 10 checklist for pre-clinical animal studies, and all efforts were made to ameliorate any suffering of animals during the experiments.18\n\nThe Ayurvedic formulation, PXT, was sampled by apex laboratories private limited (Green Milk Concepts), Kancheepuram, Tamil Nadu, India. Sildenafil Citrate (Penegra 50) and thiopental (100-150 mg/kg, i.p.) were procured from K. M. C. Pharmacy, Manipal. PXT was dissolved in 0.25% (w/v) carboxymethyl cellulose and administered orally.\n\nDopamine hydrochloride (655651-10 mg), serotonin hydrochloride (14927-25 mg) and isoprenaline (PHR2722, 250 mg) were purchased from Sigma-Aldrich (St. Louis, MO). Mass-grade formic acid, acetonitrile, and ammonium acetate were purchased from Merck (Germany). Milli-Q water was used for all reagent preparations.\n\nHydroalcoholic dry powder extracts processed from W. somnifera root, A. racemosus root, P. granatum seed, M. fragrans mace, C. arundinaceum root, O. mascula root, C. orchoides rhizome, T. terrestris fruit, C. paniculatus seed, and Shilajit exudate were obtained from Amsar Private Limited, India, and the details of their individual specifications and quality standards are provided in the repository.19 The powders along with pharmaceutical excipients were combined at specified ratios into a filing-coated tablet of 800 ± 25 mg for Code No. HTB020, which was used. The tablets were evaluated for a disintegration time of approximately 30 min, water solubility of 40%, and loss on drying of 10%. The HPTLC Chromatogram was screened and standardized for the formulation. The tablets were pulverized and used in this study. Batch number HTB020/014 was used in this study. The HPTLC chromatogram of the methanolic extract of the formulation and the respective individual plants are provided in the extended data.19\n\nA single-dose toxicity study was carried out according to the Organization for Economic Co-operation and Development (OECD) guideline 425.20 The maximum dose chosen for the limit test was 2000 mg/kg. Ten male rats were divided into two groups (n=5 each): vehicle (CMC) and treatment (PXT). One rat was dosed at a given time. Following overnight fasting (only food was withheld), PXT (2000 mg/kg) was administered orally. An equal volume of vehicle was administered to the vehicle group. After treatment, the animals were observed continuously for 14 days for any gross behavioral changes or death. Rats were sacrificed (using high-dose thiopental anaesthesia) and the weights of the brain, heart, liver, spleen, lung, kidney, and testes were noted to calculate the organ indices. Relative organ weight was calculated as follows: (organ weight (g)/body weight of the animal on the day of sacrifice (g)) × 100.21\n\n2.5.1 Grouping and treatment schedule\n\n24 healthy male Wistar rats (age~100 days) were randomly divided into four groups (n=6): vehicle control (0.25% CMC), standard control (Sildenafil Citrate 5 mg/kg), and treatment groups (PXT 50 mg/kg and 100 mg/kg). The resource equation method of sample size calculation was used to calculate the sample size. Simple randomization was performed using Microsoft Excel to allocate the animals to various groups. The maximum recommended human dose of PXT is 1 g/day.22 Sildenafil dose was selected based on previous reports.8 After an initial acclimatization period of 7 days, all rats were orally administered their respective treatments for 8 weeks. During the first 10 days of treatment, the rats were trained twice for sexual activity in the presence of an observer blinded to the treatment allocation. Sexual behavior and reproductive toxicity were assessed on 28th and 56th day, respectively.\n\n2.5.2 Screening of female rats\n\nYoung female rats (3-4 months old) were screened for regular estrous cycle.23 Briefly, vaginal rinses were collected after washing the vagina with 10 μl of normal saline using a plastic pipette. Rinses were smeared over a glass slide and observed under 10× and 40× of a light microscope. Three types of cells can be observed: round and nucleated epithelial cells, which indicate the proestrus phase, enucleated irregular cornified epithelial cells, which indicate the estrous phase, and dominant presence of leukocytes, indicating the diestrous phase.\n\n2.5.3 Sexual behavior testing\n\nSexual behavior experiments were conducted from 19:00 h to 21:00 h in a transparent acrylic chamber in a dark room with a red dim light that allowed observation.6,24 Ninety minutes after treatment, each male rat was introduced into the observation chamber and allowed to habituate for 10 min. Following this, one sexually receptive female rat (in the estrous phase) was introduced, and sexual behavior was noted for 30 min or until the first ejaculation. Following training, sexual behavior was assessed on the 28th day. The following parameters were recorded.\n\n1. Latency for mounting: The time between the first encounter of a receptive female in the arena and the first mount. Mount is when the male rat mounts the female from the back and clutches her flank with his front feet. This was used as a measure of libido or sexual desire.\n\n2. Latency for intromission: The time between the first encounter of a receptive female in the arena and the first intromission. An intromission occurs when the male achieves vaginal insertion during mounting. This was used as a measure of libido or sexual desire.\n\n3. Mount frequency: The number of mounts to ejaculation (there is no vaginal insertion during a mount). This is a measure of sexual drive\n\n4. Intromission frequency: The time between the first encounter of a receptive female in the arena and the first vaginal insertion. It is a measure of sexual arousal and erectile function.\n\n5. Ejaculation latency: Time taken from first intromission to ejaculation. This is a measure of copulatory efficiency.6,24\n\nToxicity in the reproductive system was measured after 56 days of PXT administration. Sperm count, sperm motility, sperm morphology, organ indices of the testes and seminal vesicles, and histopathology of the testes were performed to assess signs of reproductive toxicity.6 The cauda epididymis was isolated for sperm analysis. Seminal vesicles and testes were isolated for organ index calculation.\n\n2.6.1 Sperm motility\n\nBriefly, the cauda epididymis was placed in a petri dish containing 1 ml of high-glucose DMEM (Himedia, 11965092-20 ml) medium. It was cut at a few sites with a surgical blade to allow sperm diffusion. The tubule part was absorbed in DMEM to avoid contact between spermatozoa and air. Immediately, 50 μL of the sperm suspension was placed on a Neubauer hemocytometer. Fifty spermatozoa were observed in each of the four quadrants for forward motility, flagellar beating, or inertness within 5 min. The numbers of motile, wiggling, and non-motile sperm were counted.6\n\n2.6.2 Sperm morphology\n\nTen microliters of sperm suspension along with 10 μL of 0.5% eosin Y dye were placed on a clean slide. The smear was then made and air-dried. A total of 200 spermatozoa were observed for abnormalities under a bright-field microscope. Slides were observed for primary abnormalities such as headless tail, alterations in size and shape of the head, and secondary abnormalities such as a tailless head, kinked tail, and bent neck.6\n\n2.6.3 Sperm count\n\nSpermatozoa were allowed to diffuse into the medium for 10 minutes. The sperm suspension was 10-fold diluted, and 50 μL of the diluted suspension was used for counting using an improved Neubauer chamber. The total number of spermatozoa was counted in four quadrants and multiplied by the dilution factor.6\n\n2.6.4 Histopathology\n\nFollowing sacrifice, rat testes were isolated and stored in 10% neutral buffered formalin for further histological assessment. Later, testes were paraffin-embedded and sectioned coronally for hematoxylin and eosin (H&E) staining. The slides were then observed under a light microscope for histological changes.\n\n2.7.1 Brain Homogenate & Sample Preparation\n\nConcentrations of serotonin and dopamine in the brain regions responsible for sexual activity were estimated using LC-MS/MS.25 The median preoptic area and hypothalamus were isolated and frozen immediately at -80°C until further analysis. Briefly, brain samples were weighed and homogenized using Polytron PT3100D (Kinematica, Lucerene, Switzerland) at a concentration of 1g tissue/10 ml of 2% formic acid in water (ice cold) and centrifuged at 15000 rpm, 4°C for 20 min. The clear supernatant was stored at -20°C until analysis. For the analysis of samples, into a 1.5 mL conical centrifuge tube, 10 μL of isoprenaline (100 ng/mL), 100 μL of brain homogenate, and 400 μL of cold acetonitrile containing 1% formic acid were taken serially. The contents were vortexed for 30 s and centrifuged for 15 min at 12000 rpm maintaining at 4°C, and 5 μL of supernatant was injected into the LC-MS (Supplementary 1.2. section).\n\n2.7.2 LC-MS/MS analysis\n\nThe analysis was performed using a Dionex Ultimate3000 liquid chromatography coupled with a linear ion-trap LTQ-XL mass spectrometer. The Chromatographic separation was achieved using HPLC column (Synergi™ 4 μm Polar-RP 80 Å 150 × 4.6 mm) operated at 25°C at a flow rate of 0.4 mL/min with gradient programming; initially, 85%A for 0.5 min, linearly changing to 40% A at 2 min, kept constant up to 5 min, and brought back to 85%A at 6 min and conditioned with a total run time of 10 min. The mobile phase contained 0.1% formic acid in water (A) and 0.1% formic acid in methanol (B). The mass spectrometer consisted of a heated electron spray ionization source operated in positive polarity at a source heater temperature of 410°C, sheath gas flow of 50 arb, auxiliary gas flow of 16 arb, and capillary temperature of 350°C in consecutive reaction monitoring mode (Table 1). The method was linear in the range of 5.0 to 425.0 ng/mL in brain homogenates. Because the analytes were endogenous, pooled brain homogenates from the control group were used for the preparation of calibrators, and a background subtraction approach was used for the calculation of concentrations.\n\n2.8.1 Collection and target prediction of bioactives\n\nThe phytochemical constituents of PXT components, W. somnifera root, A. racemosus root, P. granatum seed, M. fragrans mace, C. arundinaceum root, O. mascula root, C. orchoides rhizome, T. terrestris fruit, C. paniculatus seed, and shilajit exudate were obtained from Dr. Duke’s Phytochemical and Ethnobotanical databases (USDA) (https://phytochem.nal.usda.gov/phytochem/search/list) and Indian Medicinal Plants Phytochemistry and Therapeutics (IMPPAT, https://cb.imsc.res.in/imppat/)26 and literature survey. The SMILES of the obtained phytocompounds were retrieved from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/). The phytocompounds were screened for bioavailability and drug-likeness using the SwissADME database.27 Chemical compounds with bioavailability scores >0.55 and more than two out of rule-of-five (Lipinski, Ghose, Veber, Egan, and Muegge) were selected as bioactive compounds. Then, the Swiss Target Prediction (STP) database (http://www.swisstargetprediction.ch/),28 PharmMapper (https://www.lilab-ecust.cn/pharmmapper/),29 and Similarity ensemble approach (https://sea.bkslab.org/#:~:text=Similarity%20ensemble%20approach%20(SEA),build%20cross%2Dtarget%20similarity%20maps)30 were used to predict the targets of bioactives. Targets with a probability greater than 0.01 were considered for STP, whereas all the targets obtained from PharmMapper and SEA were included in the study.\n\n2.8.2 Target phishing\n\nSimilarly, genes/targets related to male sexual function (MSF) were screened using the query term” male sexual function’ in GeneCards (https://www.genecards.org/)31 and NCBI gene list (https://www.ncbi.nlm.nih.gov/gene/). Only genes with a relevance score of > 10 were considered for GeneCards, whereas all the genes obtained were considered for the NCBI gene list. The relevance score is the score through which the GeneCards database ranks all genes associated with the search term.\n\n2.8.3 Common targets and construction of the Bioactive-target-MSF network\n\nThe collected bioactive and MSF targets were overlapped to identify potential targets for the improvement of sexual function. To explore the interrelationships between PXT bioactives, target genes, and MSF, a compound-target-MSF was created using Cytoscape 3.9.1 software.32 Using a network analyzer, the degree of the network was assessed to identify the key bioactive components of PXT that are involved in male sexual function.\n\n2.8.4 Gene Ontology (GO) Function Enrichment and KEGG Pathway Analysis\n\nThe Database for annotation, visualization, and integrated discovery (DAVID) software was used to generate functional pathways using GO and KEGG pathway enrichment analyses (https://david.ncifcrf.gov/tools.jsp).33 The overlapping targets were subjected to DAVID to perform functional annotation (cellular component, molecular function, and biological process). Statistically significant terms (p≤0.01) were identified, and the top 15 GO enrichment and the top 15 KEGG pathways were selected for further analysis. These pathways may be the functional mechanism of the drug, and a network was constructed using Cytoscape.\n\n2.8.5 Construction of target protein-protein interaction (PPI) Data\n\nTo identify potential targets of the drug, the overlapping targets were mapped to the STRING database version 11.0 (https://cn.string-db.org/) to obtain the potential PPI network.34 Targets related to Homo sapiens with a high confidence score > 0.4 were selected. PPI network data were exported to the Cytoscape software. The MCODE cluster analysis plugin was used to identify the prominent subregions of the PPI network. Cluster analysis was performed with a node score cutoff=0.2, K-core=2, and degree of cutoff=2. Furthermore, the Maximal Clique Centrality (“MCC”) algorithm in the “CytoHubba” plug-in was used to identify core targets from the prominent cluster, as it has high prediction accuracy.35\n\nTo verify the results from the network pharmacology studies, the binding affinity between the core targets and their related bioactive compounds was assessed. Crystal structures of the core targets AKT1 (PDB ID: 2UVM), mitogen-activated protein kinase 3 (MAPK3 PDB ID: 2ZOQ), epidermal growth factor receptor (EGFR PDB ID: 1M17), vascular endothelial growth factor (VEGFA PDB ID:1VPF), androgen receptor (AR PDB ID:1T65), and estrogen receptor 1 (ESR1 PDB ID:2BJ4) were retrieved. PDB format from the RCSB Protein Data Bank. Furthermore, the protein structures were preprocessed and prepared for docking in Schrödinger Maestro.36 A protein preparation wizard was used to preprocess the protein by filling the missing side chains and loops if any were missing in the PDB. The OPLS3e force was used to optimize the H-bonds to generate a low-energy-state protein and remove water molecules. According to the component-target interaction network, the top ten bioactive compounds were selected as ligands for docking. The structures of these compounds were retrieved from literature. sdf format from the PubChem database. Furthermore, using LigPrep available in Schrödinger Maestro, three-dimensional (3D) structures of the selected compounds were generated.37 The SiteMap tool was used to generate a grid for proteins without the co-crystallized ligand.38 A grid was generated around the site with the highest SiteScore, which had the requisite amino acid residues to modify protein activity. Glide’s extra precision (XP) and rigid docking were employed, and the docking score was recorded for each ligand with different core proteins.39 Prime MM-GBSA calculations were performed to estimate the binding energies between the ligand and receptor interactions.40 2D amino acid interactions of the ligand-protein complexes with better docking scores were noted.\n\nGraphPad Prism 8.0 software (SRC00008- https://www.graphpad.com/) was used for statistical analysis. Copyright license for the GraphPad Prism software was obtained. R is an open source alternative software which could be used for data analysis. Data were depicted as mean ± standard error of the mean (SEM). One-way analysis of variance (ANOVA) test followed by the Tukey multiple comparison test was applied. p<0.05 was considered statistically significant.\n\n\n3. Results\n\nThe results of the acute toxicity test revealed that treatment with PXT did not show any changes in behavioral patterns, skin, eyes, lacrimation, grooming signs, or postural reflex. No significant changes in body weight were observed during the follow-up period of 14 days. Importantly, all rats survived and no adverse effects were observed. Furthermore, no significant differences were observed among the organ indices of the brain, heart, lungs, liver, kidney, spleen, and testes between the vehicle- and PXT-treated groups (Figure 1). Therefore, the limit test results suggest LD50 (lethal dose for 50% of the population) for the PXT formulation to be higher than 2000 mg/kg.\n\nThe relative organ weights (organ indices) of male rats treated with a single dose of PXT for 14 days. Data represented as mean ± SEM (n=3). One-way ANOVA followed by Tukey’s multiple comparison test. No significant difference observed among the groups.\n\nThe effect of PXT on sexual activity was assessed by evaluating the copulatory behavior of experienced male rats. All the treatment groups, PXT 50 mg/kg, PXT 100 mg/kg, and sildenafil, exhibited a significant decrease in the latency for mounting (p<0.0001) and intromission (adjusted p = 0.0032, 0.0432, 0.0055, respectively) compared to the control group (Figure 2A, C). Furthermore, a marked increase (non-significant) in mount frequency was observed in the PXT 50 and PXT 100 treatment groups compared to that in the vehicle and sildenafil groups (Figure 2B). However, no significant difference in intromission frequency was observed between groups (Figure 2D). The PXT 50 and PXT 100 groups exhibited increased ejaculation latency compared with the control and sildenafil groups (Figure 2E). These results indicate that oral administration of 50 mg/kg and 100 mg/kg PXT for 28 days resulted in aphrodisiac activity, as indicated by enhanced sexual desire, sexual arousal, and copulatory efficiency in normal rats.\n\nData represented as mean ± SEM (n=6). One-way ANOVA followed by Tukey’s multiple comparison test. *p<0.05, **p<0.01 and ***p<0.001 as compared with control.\n\nA semen analysis test was carried out to study the effect of PXT treatment on the quality and quantity of sperm (sperm number, morphology, and motility). Treatment groups, sildenafil and PXT 50 showed a significant increase (adjusted p=0.0072 and 0.0066, respectively) in the number of motile sperm compared to the control (Figure 3B). Similarly, sildenafil, PXT 50, and PXT 100 significantly decreased (adjusted p=0.0150, 0.0200, and 0.0488, respectively) the number of non-motile sperm compared to the vehicle group (Figure 3B). Additionally, all treatment groups, PXT 50 (adjusted p=0.0256), PXT 100 (adjusted p=0.0012), and sildenafil (adjusted p=0.0011), demonstrated a significant increase in the sperm population compared to the vehicle group (Figure 3A). These results indicated that both doses of PXT and sildenafil possess spermatogenic potential.\n\n(A) sperm count, (B) sperm motility, and (C&D) organ indices of testes and seminal vesicles (SV) in male rats. Data represent mean ± SEM (n=6). Data were analysed by one-way ANOVA followed by Tukey’s test. *p<0.05, **p<0.01 compared with control.\n\nVarious sperm abnormalities, such as headless tail, bent neck, kinked tail, and tailless head, were observed in all groups. Among these abnormalities, bent neck and kinked tails constituted the highest percentage. The vehicle and PXT 50 groups showed a lower percentage of sperm with abnormalities than the sildenafil and PXT 100 groups. Although not statistically significant, PXT 100 showed a higher percentage of sperm with abnormalities than the control and PXT 50 groups (Table 2).\n\nTo estimate reproductive activity, indices of the reproductive organs were assessed. Although no major differences in testicular weight were observed between the control and treatment groups, a significant increase (adjusted p=0.0167) in the organ index of seminal vesicles was observed in the PXT 100 group compared to the control group (Figure 3C). This finding suggests that PXT treatment can play a role in improving seminal secretions that affect androgenic function.\n\nTo assess the reproductive toxicity of PXT following chronic treatment, histological analysis of the testes was performed. Hematoxylin and eosin staining revealed that the tissue architecture and cellular integrity of the testes were maintained in the vehicle and treatment groups. The sections revealed numerous seminiferous tubules with several layers of cells, including Sertoli cells, spermatogonia, spermatocytes, and spermatids. Importantly, all levels of spermatogenic cells were orderly and closely arranged in rows, and no histological changes such as necrosed or degenerated tubules, depletion and degeneration of germ cells, and retention of spermatids were observed in any of the treatment groups (Figure 4). These findings indicated that the doses of PXT used were not associated with any reproductive toxicity.41\n\nIntact seminiferous epithelium can be appreciated in all the groups. No signs of degeneration or abnormalities were found. G represents germinal cells, S represents spermatids and sperm cells, L represents lumen and SG represents spermatogonial cells.\n\nThe concentrations of serotonin and dopamine in the brain regions responsible for sexual activity were estimated. A representative chromatogram of the treated rat brain samples is shown in Figure 5A. In the MPOA and hypothalamus areas, DA concentrations were higher in the PXT50 group than in the control group (not significant). However, DA levels were significantly higher in the PXT50 group than in the sildenafil group (adjusted P=0.0340) (Figure 5B). These results suggest that the administration of PXT (50 mg/kg) enhanced dopamine levels in the brain regions associated with sexual behavior, potentially leading to improved sexual activity. Conversely, no significant differences in serotonin levels were observed between the groups (Figure 5C).\n\n(A) Chromatogram of PXT treated rat brain sample. Retention time of dopamine (5.39 min), 5-HT (7.49 min) and isoprenaline (6.60 min). (B) Concentration of dopamine and (C) 5-HT in brain regions associated with sexual behavior assessed using LC-MS. Data represents mean ± SEM (n=4). Data analysed by one-way ANOVA followed by Tukey’s test. *p<0.05 compared with sildenafil.\n\nA total of 126 chemical constituents of PXT were obtained from the USDA, IMPPAT, and a literature survey. Through ADME screening, 114 bioactive compounds with OB≥0.55 and more than two drug-likeness (Lipinski, Ghose, Veber, Egan, and Muegge) were chosen for further study. Furthermore, 916 unique targets were predicted for 114 bioactive compounds using STP, SEA, and PharmMapper.\n\nUsing “Male sexual function” as the search term, 1083 targets related to MSF were retrieved from the GeneCards, NCBI gene, and TTD databases. Among the 916 bioactive targets and 1007 MSF-related targets, 215 common targets were identified, indicating their potential involvement in MSF. The PXT-MSF common target network contained 327 nodes (94 bioactive, 223 target genes) and 1569 edges was established. Degree analysis indicated that macelignan, somniferine, estradiol, and testosterone possess a higher number of targets that could influence MSF. Furthermore, a significant number of bioactive compounds targeted key players such as the AR, CYP19A1 (aromatase), PTGS2 (cyclooxygenase), HSD11B1 (hydroxysteroid 11-beta dehydrogenase 1) and acetylcholinesterase (ACHE), suggesting their possible role in improving male sexual function (Figure 6).\n\nEllipses represent the potential bioactives of PXT that affect MSF. Arrow heads represent MSF-related target genes. Nodes are size sorted based on color.\n\nGO enrichment analysis was performed to understand the biological information of 215 overlapping genes. This analysis revealed 832 enriched GO terms with a significance level of p<0.01, consisting of 648 biological processes, 75 cellular components, and 109 molecular functions (Figure 7A). The principal biological processes include positive regulation of transcription from the RNA polymerase II promoter, signal transduction, and positive regulation of gene expression. Additionally, these genes were mainly related to functions such as protein binding, identical protein binding, and ATP binding. The major cellular components of these genes are the plasma membrane, cytoplasm, and the nucleus.\n\n(A) GO enrichment analysis of the target genes; (B) KEGG enrichment analysis of the target genes. The x-axis shows the number of genes enriched in the pathway. The size of bubbles represents the number of targets in the pathway and the color represents the p value.\n\nTo explore the enriched signalling pathways related to the 215 candidate genes, KEGG pathway analysis was performed. The analysis identified that most targets were enriched in the PI3K-Akt signalling pathway, MAPK signalling pathway, and calcium signalling pathways, all of which are closely associated with male sexual function (Figure 7B).\n\nThe C-T-P network was built to provide a holistic understanding of PXT bioactives, their targets, and their associated pathways in male sexual function. As shown in Figure 8, the network was subjected to topological analysis. Based on the degree value, macelignan, paniculatine, nicotiflorin, estradiol, ellagic acid, testosterone, kaempferol, quercetin, paniculatine, and withanolide P were identified as 10 significant bioactive compounds with high degrees of MSF targets. AR, HSD11B1, PRKCA, CYP19A1, PTGS2, KDR, MAPK1, ACHE, and PIK3CA were identified as the top 10 crucial targets in the compound-target-pathway network (Figure 8).\n\nEllipses represent the potential bioactives of PXT that affect MSF. Diamonds represent the important pathways involved in PXT action toward MSF. Arrow heads represent MSF-related target genes. Nodes are size sorted by color.\n\nPPI network analysis was performed to identify key targets responsible for mediating the effects of PXT on MSF. The 215 candidate genes involved in MSF were used to construct a PPI with a confidence (score) cut-off of 0.4. A PPI interaction network consisting of 215 nodes and 3827 edges was generated in the cytosol (Figure 9A). MCODE cluster analysis of the PPI network resulted in 11 clusters. Cluster 1 had the highest clustering coefficient of 45.279 and was therefore considered as the prominent subnetwork of the PPI (Figure 9B). The core targets of the cluster 1 subnetwork were analyzed using the MCC′ algorithm of the Cytohubba plug-in. Analysis revealed AKT1, MAPK3, EGFR, ESR1, and VEGF as core targets involved in the action of PXT against MSF (Figure 9C). In addition, these targets are associated with the PI3K-AKT pathway, which is the top signalling pathway involved in PXT action. Because AR is the most significant target in the PXT-MSF and C-T-P networks, it is also included as the key target.\n\n(A) PPI network of PXT target genes for MSF (B) Cluster with high cluster co-efficient generated after cluster analysis of PPI network; (C) Core targets obtained after ranking by MCC algorithm of Cytohubba application.\n\nFollowing the network analysis results, molecular docking analysis was conducted to validate the binding between the core targets (AKT1, VEGFA, MAPK3, ESR1, AR, and EGFR) and key bioactive compounds obtained from the C-T-P network. Table 3 displays the binding scores, which indicate the potential binding of most bioactive compounds to the active sites of their respective targets. Figure 10 illustrates the molecular interactions of bioactive compounds with the highest scores. The amino acid interactions of proteins with their respective ligands and their hydrogen bond lengths are listed (Table 3). Most bioactive compounds exhibited hydrophobic and polar interactions with core targets. Quercetin docked with AKT1 through hydrogen bonding with inhibitory A. A residues, ARG86, and ASN53. In addition, the docking score and binding affinity were better than those of the known Akt1 inhibitor capivasertib. Testosterone, followed by beta-estradiol and quercetin, exhibited better binding affinity and docking score with AR, forming hydrogen bonds with the A. A residues ASN705, THR877, and GLN711 required for activation. Ellagic acid showed a better binding affinity with ESR1. Nicotiflorine, followed by quercetin and kaempferol, showed better binding affinities for EGFR and VEGF. Quercetin and ellagic acid showed improved binding to MAPK3.\n\n* Represents known activator/inhibitor.\n\n(A) Nicotiflorine-AKT1; (B) Ellagic acid-ESR1; (C) Nicotiflorine-EGFR; (D) Ellagic acid-MAPK3; (E) Nicotiflorine-VEGF. Purple arrows indicate hydrogen bonding. Green lines indicate pi-pi interactions.\n\n\n4. Discussion\n\nChronic exposure to diverse insults, such as lifestyle factors, occupational stressors, aging, and environmental toxins can gradually disrupt male sexual function. Consequently, the development of a single drug to improve male sexual function poses a challenge. Moreover, the continuous consumption of such drugs may lead to numerous side effects. In contrast, traditional plant-based medicine, with its unique polypharmacology approach, offers significant advantages in treating complex and multifactorial diseases, such as sexual dysfunction. In addition, it is a safer alternative that can be routinely consumed by a healthier population. PXT is an Ayurvedic formulation that enhances male sexual function in a healthy population. However, the principal bioactivity of PXT and the underlying mechanisms responsible for its aphrodisiac action remain unknown.\n\nThe current study demonstrated that oral administration of the PXT formulation is safe up to 2000 mg/kg. Administration of PXT (50 mg/kg and 100 mg/kg) to male Wistar rats enhanced libido (sexual desire) and sexual arousal, as evidenced by decreased mount and intromission latencies and increased mount and intromission frequency. Compared to the control, PXT-treated rats showed increased ejaculation latency and prolonged duration of coitus, which indicates an increase in sexual motivation and copulatory performance. Studies suggest that ejaculation latency below 300 s indicates premature ejaculation, and above 1200 s indicates delayed ejaculation in rats.42 In the present study, PXT improved the ejaculation time of the rats within this range.\n\nWith respect to their integral role in various phases of sexual behavior, DA and 5-HT levels were estimated in the brain regions (MPOA and hypothalamus) associated with sexual behavior. DA serves as the principal neurotransmitter responsible for sexual motivation, copulatory efficiency, and genital reflexes,43 whereas 5-HT is known to have an inhibitory role in sexual behavior.3 Interestingly, PXT 50 mg/kg PXT increased brain DA concentrations without altering 5-HT levels. This indicates that PXT 50 facilitates copulatory behavior by enhancing the dopamine tone. Similarly, a previous study reported that E. longifolia treatment elevated cortical and hippocampal dopamine levels, whereas 5-HT levels remained unaffected.44\n\nFurthermore, 50 mg/kg and 100 mg/kg PXT exhibited spermatogenic potential with increased viable sperm count and motility, which could be advantageous in treating oligospermia. However, an increased percentage of sperm abnormalities was observed in the 100 mg/kg PXT group compared to that in the other groups. Nonetheless, this was below 10%, indicating that PXT is free of reproductive toxicity at the recommended doses, even after treatment for 56 days. This was also supported by the preserved normal histology of the testes in PXT-treated rats.\n\nAlthough several studies have indicated the aphrodisiac efficacy of whole plant extracts, limited knowledge exists regarding the exact bioactive compounds responsible for its beneficial action. To explore the bioactives, mechanisms, and molecular targets underlying the beneficial effects of PXT on male sexual function, we employed an integrated network pharmacology and molecular docking approach. The compound-target-pathway network analysis revealed that macelignan, paniculatine, nicotiflorin, β-estradiol, ellagic acid, testosterone, kaempferol, quercetin, paniculatine, and withanolide P had the maximum number of targets that could influence male sexual function. Previous studies have demonstrated that a few plant compounds, including beta-estradiol,45 ellagic acid,46 and kaempferol,47 improve fertility and male sexual function in animal models. Quercetin has also been shown to improve male sexual function in several animal models.48 However, the mechanisms by which they exert their actions are limited.\n\nOur study demonstrated that PI3K-Akt signalling and MAPK signalling pathways might be crucial among the multiple signalling pathways through which PXT may improve male sexual function. Supporting studies have indicated that male reproductive functions, including the endocrine function of gonads and spermatogenesis, are regulated by PI3K-Akt signalling, and its dysregulation has been implicated in erectile dysfunction.49,50 Through PPI interactome analysis, AKT1, VEGFA, ESR1, and EGFR were found to be the key targets of PXT in MSF. AR was also considered as a key target because it had the highest degree in the C-T-P and PXT-MSF common target networks.\n\nAkt is a serine/threonine protein kinase that plays a fundamental role in cellular processes such as proliferation, cell growth, metabolism, and apoptosis. The Akt1 isotype is involved in spermatogenesis and testicular development.51,52 Studies have also suggested that PI3K/AKT1 signalling through eNOS activation is responsible for penile erection and male sexual activity.53 Our findings showed that quercetin and nicotiflorine had good binding affinities with Akt1. Supporting studies have also suggested that quercetin improves testicular injury and reproductive performance by attenuating oxidative stress via AKT modulation.54 This suggests that PXT might improve MSF through a PI3-kinase/Akt signalling mechanism.\n\nIn addition to PI3-kinase/Akt signalling, androgen and estrogen signalling via the AR and ESR are critical for male gonad development, erectile function, and spermatogenesis during development and adulthood.55 In addition to estradiol and testosterone, which are endogenous ligands of AR and ESR1, respectively, the current study showed that many phytoconstituents of PXT, such as ellagic acid, macelignan, and kaempferol, exhibited good binding affinities with AR and ESR1. This suggests that PXT may improve MSF through androgen and estrogen signalling.\n\nFurthermore, VEGF is reported to have a direct trophic effect on penile smooth muscles, and treatment with VEGF supplementation is administered for erectile dysfunction of smooth muscle integrity issues.56 The current study showed a good binding affinity of ellagic acid, quercetin, and kaempferol to VEGF. Additionally, MAPK signalling has been linked to erectile dysfunction by promoting endothelial dysfunction, apoptosis, and fibrosis.57 Quercetin and ellagic acid showed good binding affinities for MAPK3. This suggests that PXT might improve MSF through the VEGF and MAPK3 signalling pathways.\n\n\n5. Conclusion\n\nAltogether, our study results suggest that PXT could be a safer and promising alternative that exhibits aphrodisiac and spermatogenic potential. This could be partly attributed to its ability to enhance the dopaminergic tone. In this study, we identified macelignan, estradiol, testosterone, quercetin, and ellagic acid as potential bioactive compounds in PXT, acting through multiple mechanisms to enhance male sexual function.\n\n\nDeclarations\n\nThis study was approved by the Institutional Animal Ethics Committee (IAEC/KMC/50/2022).\n\n\nConsent for publication\n\nNot applicable.",
"appendix": "Data availability\n\nFigshare: Data related to Network pharmacology studies, https://doi.org/10.6084/m9.figshare.24711369.v1. 19\n\nThe data contains the following underlying data\n\n• PXT compounds and targets: targets related to the PXT bioactives\n\n• Disease genes: Genes involved in Male sexual function\n\n• Network analysis: Common targets, protein-protein interactions, network analysis, identification of hubs, pathways through which PXT might modulate the male sexual function, docking scores\n\nCreative Commons Attribution 4.0 International license (CC-BY 4.0)\n\nSupplementary data: HPTLC fingerprints of each plant present in the PXT formulation\n\nFigshare: Effect on testicular histology, https://doi.org/10.6084/m9.figshare.25249192.v1. 41\n\nThe data contains the representative photographs showing H&E stained testicular histology.\n\nCC BY 4.0\n\nFigshare: ARRIVE checklist for ‘Poweromin X Ten, a polyherbal formulation improves male sexual function: in vivo and network pharmacology study’ https://doi.org/10.6084/m9.figshare.24763458.v1 18\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 acknowledge Mr. S.S. 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PubMed Abstract | Publisher Full Text\n\nOlabiyi AA, AlliSmith YR, Ukwenya VO: Quercetin Enhances Sexual Behavior and Improves Ectonucleotidases Activity in the Hypothalamus of Rats Treated with Cyclosporine. J. Food Biochem. 2021; 45(8): e13864. Publisher Full Text\n\nDeng C-Y, Lv M, Luo B-H, et al.: The Role of the PI3K/AKT/MTOR Signalling Pathway in Male Reproduction. Curr. Mol. Med. 2021; 21(7): 539–548. PubMed Abstract | Publisher Full Text\n\nDing J, Tang Y, Tang Z, et al.: Icariin Improves the Sexual Function of Male Mice through the PI3K/AKT/ENOS/NO Signalling Pathway. Andrologia. 2018; 50(1): e12802. PubMed Abstract | Publisher Full Text\n\nChen WS, Xu PZ, Gottlob K, et al.: Growth Retardation and Increased Apoptosis in Mice with Homozygous Disruption of the Akt1 Gene. Genes Dev. 2001; 15(17): 2203–2208. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCho H, Thorvaldsen JL, Chu Q, et al.: Akt1/PKBα Is Required for Normal Growth but Dispensable for Maintenance of Glucose Homeostasis in Mice. J. Biol. Chem. 2001; 276(42): 38349–38352. PubMed Abstract | Publisher Full Text\n\nHurt KJ, Musicki B, Palese MA, et al.: Akt-Dependent Phosphorylation of Endothelial Nitric-Oxide Synthase Mediates Penile Erection. Proc. Natl. Acad. Sci. USA. 2002; 99(6): 4061–4066. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang X, Tang Y, Lu G, et al.: Pharmacological Activity of Flavonoid Quercetin and Its Therapeutic Potential in Testicular Injury. Nutrients. 2023; 15(9). PubMed Abstract | Publisher Full Text | Free Full Text\n\nCripps SM, Mattiske DM, Pask AJ: Erectile Dysfunction in Men on the Rise: Is There a Link with Endocrine Disrupting Chemicals? Sex. Dev. 2021; 15(1–3): 187–212. PubMed Abstract | Publisher Full Text\n\nRogers RS, Graziottin TM, Lin CS, et al.: Intracavernosal Vascular Endothelial Growth Factor (VEGF) Injection and Adeno-Associated Virus-Mediated VEGF Gene Therapy Prevent and Reverse Venogenic Erectile Dysfunction in Rats. Int. J. Impot. Res. 2003; 15(1): 26–37. PubMed Abstract | Publisher Full Text\n\nLiu K, Sun T, Luan Y, et al.: Berberine Ameliorates Erectile Dysfunction in Rats with Streptozotocin-Induced Diabetes Mellitus through the Attenuation of Apoptosis by Inhibiting the SPHK1/S1P/S1PR2 and MAPK Pathways. Andrology. 2022; 10(2): 404–418. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "271367",
"date": "17 Jul 2024",
"name": "Akingbolabo Daniel Ogunlakin",
"expertise": [
"Reviewer Expertise Pharmacognosy",
"and Biochemistry"
],
"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. Authors need to mention the determination of LD50 in the abstract.\n2. Preparation of standard extract of PXT Hydroalcoholic dry powder extracts processed from W. somnifera root, A. racemosus root, P. granatum seed, M. fragrans mace, C. arundinaceum root, O. mascula root, C. orchoides rhizome, T. terrestris fruit, C. paniculatus seed, and Shilajit exudate were obtained from Amsar Private Limited, India, and the details of their individual specifications and quality standards are provided in the repository.19 The powders along with pharmaceutical excipients were combined at specified ratios into a filing-coated tablet of 800 ± 25 mg for Code No. HTB020, which was used. I wonder how the authors got the formation right since PXT is a formulation in the market. Is PXT their patent? This need to be clarified.\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": "12263",
"date": "28 Aug 2024",
"name": "Sree Bojja",
"role": "Author Response",
"response": "Reviewer comment 1. Authors need to mention the determination of LD50 in the abstract. Response: LD50 evaluation and results are now added to the abstract. ‘Acute oral toxicity evaluation of PXT indicated LD50 greater than 2000 mg/kg.’ Comment 2. Preparation of standard extract of PXT. I wonder how the authors got the formation right since PXT is a formulation in the market. Is PXT their patent? This need to be clarified. Response: PXT is an Ayurvedic Proprietary Medicine of Apex laboratories Pvt. Ltd, and the company has provided the composition of the formulation and its characterisation profile."
}
]
},
{
"id": "293968",
"date": "20 Aug 2024",
"name": "Idris Adewale Ahmed",
"expertise": [
"Reviewer Expertise Pharmacology"
],
"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 the manuscript titled: “Poweromin X Ten, a polyherbal formulation improves male sexual function: In vivo and network pharmacology study”, the authors investigated the toxicity and aphrodisiac potential of PXT in male rats and explored its principal mechanisms of action.\n\nThe general logic of the article is fairly integral, however, some issues require clarification, especially in the methodology and result sections.\nThe title is appropriate and the abstract is comprehensive. The introduction and the methodology are concise and well-presented. The composition of the standard pellet, however, should be highlighted. There were some inconsistencies in the use of symbols: “l” or “L; “min” or “minutes”. The sub-section 2.7.1 uses “Capitalize each word” in contrast to the rest of the sections and sub-sections (sentence case). In 3.1, the authors stated that “no significant differences were observed among the organ indices of the brain, heart, lungs, liver, kidney, spleen, and testes between the vehicle- and PXT-treated groups (Figure 1).”, however, the increase in the liver and spleen should be highlighted and some explanations on the possible causes should be provided. In 3.2: for the intromission frequency and 3.7: for DA concentration; the 50 mg/kg group had higher results than the 100 mg/kg groups. Explanations should be provided for this. Some claims in the “Discussion” especially the first paragraph should be substantiated with references.\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": "12269",
"date": "28 Aug 2024",
"name": "Sree Bojja",
"role": "Author Response",
"response": "Comment1: The composition of the standard pellet, however, should be highlighted. Response: PXT is an Ayurvedic Proprietary Medicine of Apex laboratories Pvt. Ltd, and therefore, the standardized composition cannot be disclosed in the manuscript Comment 2: There were some inconsistencies in the use of symbol: “l” or “L:; “min” or “minutes”. Response: The terms ‘minutes’ and ‘L’ are now used uniformly. Comment 3: The sub-section 2.7.1 uses “Capitalize each word” in contrast to the rest of sections and sub-sections (sentence case). Response: 2.7.1 Title is now corrected. Comment 4: In 3.1, the authors stated that “no significant differences were observed among the organ indices of the brain, heart, lungs, liver, kidney, spleen, and testes between the vehicle- and PXT-treated groups (Figure 1).”, however, the increase in the liver and spleen should be highlighted and the some explanations on the possible causes should be provided. Response: We thank you for the attention. The observed increase in the liver and spleen organ indices compared to the control group was marginal and statistically insignificant. Therefore, it does not raise any significant concerns. However, this slight increase may indicate that the liver plays a major role in the metabolism of PXT. Comment 5: In 3.2: for the intromission frequency and 3.7: for DA concentration; the 50 mg/kg group had higher results than 100 mg/kg groups. Explanations should be provided for this, too. Response: Thank you for raising an important point. The following explanation is now added in the manuscript. ‘The effect of PXT 50mg/kg on mount latency, intromission latency, and intromission frequency was slightly more pronounced than with PXT 100mg/kg. This difference might be attributed to a relatively greater increase in brain dopamine levels induced by PXT 50mg/kg compared to PXT 100mg/kg. While the reduced dopamine levels by PXT 100mg/kg could be as a result of enhanced dopamine metabolism, possibly due to compensatory mechanisms that are activated at higher dosages.’ Comment 6: Some claims in the “Discussion” especially in the first paragraph should be substantiated with relevant references. Response: References are added to the necessary statements in the discussion part."
}
]
}
] | 1
|
https://f1000research.com/articles/13-260
|
https://f1000research.com/articles/13-642/v1
|
17 Jun 24
|
{
"type": "Brief Report",
"title": "Evaluation of centralised and decentralised models of care during the 2020 Ebola Virus Disease outbreak in Equateur Province, Democratic Republic of the Congo: A brief report",
"authors": [
"Emmanuel Lampaert",
"Justus Nsio Mbeta",
"Divya Nair",
"Maria Mashako",
"Anja De Weggheleire",
"Armand Sprecher",
"Rebecca M. Coulborn",
"Steve Ahuka-Mundeke",
"Justus Nsio Mbeta",
"Divya Nair",
"Maria Mashako",
"Anja De Weggheleire",
"Armand Sprecher",
"Rebecca M. Coulborn",
"Steve Ahuka-Mundeke"
],
"abstract": "Background Traditionally in the Democratic Republic of the Congo (DRC), centralised Ebola treatment centres (ETCs) have been set exclusively for Ebola virus disease (EVD) case management during outbreaks. During the 2020 EVD outbreak in DRC’s Equateur Province, existing health centres were equipped as decentralised treatment centres (DTC) to improve access for patients with suspected EVD. Between ETCs and DTCs, we compared the time from symptom onset to admission and diagnosis among patients with suspected EVD.\n\nMethods This was a cohort study based on analysis of a line-list containing demographic and clinical information of patients with suspected EVD admitted to any EVD health facility during the outbreak.\n\nResults Of 2359 patients with suspected EVD, 363 (15%) were first admitted to a DTC. Of 1996 EVD-suspected patients initially admitted to an ETC, 72 (4%) were confirmed as EVD-positive. Of 363 EVD-suspected patients initially admitted to a DTC, 6 (2%) were confirmed and managed as EVD-positive in the DTC. Among all EVD-suspected patients, the median (interquartile range) duration between symptom onset and admission was 2 (1-4) days in a DTC compared to 4 (2-7) days in an ETC (p<0.001). Similarly, time from symptom onset to admission was significantly shorter among EVD-suspected patients ultimately diagnosed as EVD-negative.\n\nConclusions Since <5% of the EVD-suspected patients admitted were eventually diagnosed with EVD, there is a need for better screening to optimise resource utilization and outbreak control. Only one in seven EVD-suspected patients were admitted to a DTC first, as the DTCs were piloted in a limited and phased manner. However, there is a case to be made for considering decentralized care especially in remote and hard-to-reach areas in places like the DRC to facilitate early access to care, contain viral shedding by patients with EVD and ensure no disrupted provision of non-EVD services.",
"keywords": [
"Viral Haemorrhagic Fever",
"Central Africa",
"SORT IT",
"Outbreak",
"Epidemic response",
"Decentralized care",
"Operational Research",
"Ebola"
],
"content": "Introduction\n\nEbola virus disease (EVD) is a rare but deadly viral haemorrhagic fever with an average case fatality rate of 50% (ranging between 25-90%) among those infected.1 Though vaccines and curative treatments are available, successful containment of an EVD outbreak is largely dependent on early detection, isolation, and treatment of cases.2\n\nThe Democratic Republic of the Congo (DRC) in Central Africa has experienced 15 EVD outbreaks since 1976.3 In the DRC, patients with EVD have been managed through an EVD-centric approach, at EVD treatment centres (ETCs) which are constructed in locations with large numbers of cases and which function parallel to the existing healthcare delivery system. However, recent outbreaks in the DRC and elsewhere revealed that local communities associated ETCs with remoteness and death and were reluctant to seek care from these facilities.4–7 These beliefs led to delays in admission which in turn adversely impacted survival.\n\nTo address these concerns, a strategy of decentralization was piloted during the 11th EVD outbreak, which occurred in 2020 in Equateur Province, DRC. Small teams, diagnostics, and supportive treatment services were deployed in existing local health centres in hard-to-reach areas to improve accessibility and allay communities’ apprehensions regarding ETCs. These were known as Decentralised Treatment Centres (DTCs). This approach aimed at reducing the risk of EVD transmission through early isolation of cases and improving patient outcomes through early access to diagnosis and supportive treatment while also ensuring that non-EVD health services continued to be provided to the communities.\n\nThe decentralized approach in the Equateur province has not yet been evaluated. The province merits attention in view of its large geographic expanse, tropical ecosystem conducive to re-emergence of EVD, presence of hard-to-reach pockets and a predominantly rural population which set it apart from most provinces of the DRC. Five of the fifteen outbreaks in the DRC have occurred in and around this province.3\n\nThis study therefore aimed to report on the utilization of decentralized facilities and whether these facilities helped promote early admissions and early diagnosis during the 2020 EVD outbreak in Equateur. This information can be used in preparation for future outbreaks, in terms of resource allocation, training of human resources and provision of EVD management infrastructure at existing health centres in the country.\n\n\nMethods\n\nThis was a cohort study making secondary use of data collected primarily for clinical purposes.\n\nGeneral setting\n\nThe DRC is the largest country in central Africa with a population of 112 million as of 2023.8,9 It is one of the five poorest countries globally.8 Equateur is one of its 26 administrative provinces with a population of 1.6 million and is divided into 18 health zones (Figure 1). Each health zone provides services to a population of 100,000-200,000, and is further divided into health areas for every 10,000 population.10\n\n(Source: Geographic Information System Centre, Médecins Sans Frontières).\n\nAbbreviations: ETC=Centralised Ebola treatment centre, CTD=Decentralised treatment centre, TC=Transit centre.\n\nThe DRC has a three-tier public health system: primary health centres in every health area, a secondary “General Reference Hospital” in each health zone and a tertiary “Provincial Hospital” in each provincial capital. Services in these facilities are provided on payment of user fees by the patients.10 Mbandaka, the provincial capital of Equateur, is around 1200 km by road from the national capital of Kinshasa. Within the province, the Congo river system is the major channel for transport and there is limited road connectivity.\n\nSpecific setting: EVD Outbreak of 2020\n\nThe outbreak occurred in Equateur between 1st June 2020 and 18th November 2020.11 It produced 130 cases (119 confirmed and 11 probable), of which 75 recovered and 55 died.3,12 Outbreak response was coordinated by the Ministry of Health (MOH) with technical support from multiple international aid organizations. Case definitions followed the World Health Organization recommendations.13 All EVD care services were provided free of cost during the outbreak.\n\nIn the initial period, suspected cases were admitted to ETCs which were set up exclusively for EVD care. These centres were equipped with isolation units, diagnostic facilities, and advanced treatment modalities including monoclonal antibodies (Table 1). A total of nine ETCs were newly constructed (mostly semi-temporary structures) during the outbreak (Figure 1).\n\n\n\n1. Self-referral: Any EVD-suspected case who approached the centre for care\n\n2. Referral of symptomatic EVD-contacts or EVD-contacts with a strong epidemiological link by health workers\n\n3. Referral from decentralized treatment centres\n\n4. Referral from transit centre\n\n\n\n1. Self-referral: Any EVD-suspected case who approached the centre for care\n\n2. Referral of symptomatic EVD-contacts or EVD-contacts with a strong epidemiological link by health workers\n\n\n\n• Medical doctors and nurses with expertise in EVD\n\n• Round the clock presence of experts- local and central expertise from MOH and/or external aid partnersa\n\n\n\n• Nurses involved in primary health care service delivery (with basic orientation training in EVD)\n\n• Led by local MoH staff with technical support from experts if and when required\n\na Includes Médecins Sans Frontières, The Alliance for Medical Action, and International Medical Corps\n\nb Inmazeb was approved by FDA during this outbreak (October 14 2020)\n\nSeven transit centres (TCs) were also established in places where there was no testing capacity. Samples were taken from suspected cases and transported to ETCs. Patients were kept in isolation at the TCs while awaiting laboratory results. These TCs were also considered as centralized centres, functioning parallel to the existing medical system. Some of the TCs were converted into ETCs over time.\n\nAs the outbreak progressed, suspected cases were reported from remote health zones and a decentralized approach was piloted. This approach was developed by the MOH in consultation with Médecins Sans Frontières (MSF). Based on contact tracing and epidemiological investigations, health areas where cases would be expected were identified. In these areas, the existing health centres were equipped to be decentralized treatment centres (DTCs). The first DTC started functioning in July 2020; 15 DTCs were established during the outbreak. Table 1 provides a description of the services provided at the ETCs and DTCs.\n\nAll patients with suspected EVD admitted to any EVD health facility during the 2020 EVD outbreak in Equateur were included.\n\nThe MOH maintained a compiled line-list of patients with suspected EVD admitted to any EVD health facility, and this constituted the data source. Data on patient demographic characteristics, clinical characteristics at the time of presentation, final diagnosis, and treatment outcomes were extracted from the line-list and analysed using STATA (version 16.0, StataCorpLLC, College Station, Texas, USA). R is an open-access software which can be used to conduct the same analysis.\n\nTime to admission was calculated as the duration between the date of symptom onset and date of first admission. Time to diagnosis was calculated as the duration between the date of symptom onset and date of the first positive PCR test (for confirmed cases) or date of the earliest negative PCR test (for non-EVD cases). Date of treatment initiation was not recorded in the line-list, and therefore time taken to initiate treatment could not be assessed. For patients transferred from one facility to another, the outcome reported at the final EVD health facility was considered as the final outcome.\n\nTime to admission and diagnosis were summarized as medians with inter-quartile ranges and compared between the two types of facilities (i.e., ETC versus DTC) using Mann Whitney-U test. Final outcomes between the two were compared using the Chi-square test. A p-value < 0.05 was considered statistically significant.\n\n\nResults\n\nThere were 2359 line-listed unique patients suspected of having EVD. Of these, the type of EVD health facility visited first was an ETC for 1996 (85%) patients and a DTC for 363 (15%) patients. Of the 1996 patients with suspected EVD who were initially admitted to an ETC, 72 (4%) were confirmed as EVD-positive. Of the 363 patients with suspected EVD who were initially admitted to a DTC, 6 (2%) were confirmed as EVD-positive in the same health facility and remained there for care (Figure 2).\n\n*These two patients were diagnosed as EVD-negative in the first ETC but were eventually confirmed as EVD-positive in the next ETC that they consulted.\n\nETC=Centralised Ebola treatment centre, DTC=Decentralised treatment centre, EVD = Ebola Virus Disease, EVD+=EVD-positive; EVD-=EVD-negative.\n\nTable 2 shows the demographic and clinical characteristics of patients with suspected EVD based on the type of EVD health facility first visited. The age and gender distribution were not significantly different between the two types of facilities. In total, 895 (45%) patients with suspected EVD who first visited an ETC and 137 (38%) who first visited a DTC were not vaccinated. At the time of admission, certain signs or symptoms were reported by a significantly higher proportion of patients with suspected EVD who visited an ETC first compared to a DTC, for example: fatigue (75% vs 54%), muscle pain (35% vs 20%), breathlessness (13% vs 4%), bleeding (7% vs 3%), and dysphagia (7% vs 3%). Apart from EVD, the most common final diagnosis included malaria in 954 (48%) patients first admitted to an ETC and 57 (16%) patients first admitted to a DTC.\n\na A patient could have multiple symptoms\n\nb Not applicable: Chi-square or Fisher’s exact test could not be applied due to the small numbers in cells\n\nc Other diagnosis included anaemia, fever of unknown origin, malnutrition and those entries in which “Other pathologies” was mentioned without specifying a diagnosis\n\nd Final status remained as “Probable EVD” or “Suspected EVD” in these patients: Reason is not clear from the available data and may be a data entry error or due to the fact that the patient left or died before a final diagnosis could be established.\n\nTable 3 shows a comparison of pre-diagnostic delays based on the type of facility visited first. When all patients with suspected EVD were considered, the duration between symptom onset and admission to an EVD health facility was significantly shorter among those first admitted in a DTC (Median: 2 days, Interquartile range [IQR]: 1-4 days) compared to an ETC (Median: 4 days, IQR: 2-7 days). Similarly, the duration between symptom onset and diagnosis was significantly shorter among those first admitted in a DTC (Median: 3 days, IQR: 2-6 days) compared to an ETC (Median: 4 days, IQR: 2-7 days).\n\nAmong patients with suspected EVD who were later confirmed to be EVD-positive, there was no significant difference in the time to admission and time to diagnosis based on the type of facility (Table 3).\n\nAmong the patients with suspected EVD for which the final status was EVD-negative, the duration between symptom onset and admission among those first admitted to a DTC (Median: 2 days, IQR: 1-4 days) was significantly shorter than among those who were first admitted to an ETC (Median: 4 days, IQR: 2-7 days). Also, the time to diagnosis was significantly shorter among EVD-negative patients first admitted to a DTC compared to an ETC (Table 3).\n\nThe final outcomes of the 78 EVD-positive patients are shown in Table 4. Among the 72 EVD-positive patients first admitted in an ETC, 60 (83%) were cured and 10 (14%) died. All six EVD-positive patients first admitted in a DTC were cured.\n\n\nDiscussion\n\nTo our knowledge, this is the first study exploring the decentralised model of care piloted during the 2020 EVD outbreak in the Equateur province of DRC. The study has three key findings. First, one out of seven patients with suspected EVD was first admitted to a DTC. Second, DTCs managed to reduce the time to admission diagnosis in all patients with suspected EVD (including some diagnosed later as EVD-negative). Third, 3% of all patients with suspected EVD were confirmed to have EVD. There were 12 EVD deaths in ETCs and none in a DTC.\n\nThe piloting of the DTC model marks a paradigm shift in outbreak control in the region – from a mostly EVD-centric approach to a more community-centric approach.14–17 The DRC’s “Strategic response plan for the EVD outbreak: 2018” calls for strengthening existing heath facilities and empowering the existing health workforce to conduct efficient EVD triage, maintain continuity of EVD and non-EVD care, and take healthcare closer to communities so that individuals can seek care early.16\n\nThe study has certain limitations. Since the dates of treatment initiation were missing for the majority of the patients, we could not evaluate the time taken to initiate treatment at ETCs compared to DTCs. Confounders like severity of illness (cycle threshold values) and the geographic proximity of patients to an EVD health facility might have impacted the time to admission, but we were unable to adjust for these due to the non-availability of data. These parameters should be meticulously documented in future outbreaks to enable a comprehensive evaluation of the DTC model. Given the small number of cases in this outbreak, we are unable to comment on whether the reduction in time to admission led to a difference in outcomes among patients first admitted to a DTC compared to an ETC. We were also unable to conduct qualitative interviews among patients and caregivers in these facilities, which could have provided in-depth insights into patient and provider perspectives around care seeking and delivery during the outbreak.\n\nDespite these limitations, this study has important implications, more so because this is the first study exploring a decentralised model in the Equateur Province. Only 15% of the patients with suspected EVD in the 2020 outbreak first sought care in a DTC. This could be due to the fact that the DTCs were piloted one month into the outbreak in a limited and phased manner. Therefore, the ETCs bore the brunt of cases during the outbreak.\n\nThe DTCs appear able to reduce the time taken to admit and diagnose (EVD or non-EVD) patients with suspected EVD. This has two implications. First, DTCs could provide diagnosis and care to patients with other conditions during the outbreak. In countries like the DRC, a wide spectrum of febrile illnesses like malaria and viral haemorrhagic fevers are prevalent.18–20 As care provision for these illnesses has been disrupted during previous EVD outbreaks in this region,21,22 the establishment of DTCs might help overcome this issue. Second, the median time to admission was three days in the DTCs which was slightly lower than that reported in previous outbreaks in the DRC.23,24 A reduction in time to admission and diagnosis among confirmed EVD patients could be crucial for initiating early EVD specific treatment and thus reducing mortality.1,25\n\nAll six of the patients with confirmed EVD who first visited a DTC were diagnosed and cured at the same facility (i.e., the one initially visited). These patients might have had milder forms of disease which did not require referral. While this represents too small a number from which to draw firm conclusions on the effect of decentralised care on patient outcomes among those EVD-positive and could also be influenced by the severity of illness in those presenting to the DTC, it is an encouraging finding.\n\nThere is need to look at this model critically. Only 3% of all patients with suspected EVD admitted to a treatment centre were eventually diagnosed as EVD-positive. The 2020 outbreak resulted in 130 cases, among which 55 died.3 However, only 78 patients (10 of whom died) were admitted to an EVD health facility. The rest of the patients were identified during contact tracing but could not be located or brought to a facility. The majority of deaths happened in the community, which indicates that severely ill patients who needed urgent care either did not seek care or could not be provided with care. More needs to be done to ensure that people have access to timely diagnostics and medical care. A qualitative exploration of the circumstances which led to these community deaths might be useful to understand why these individuals did not or could not access facility-based care. Also, since <5% of the patients admitted with suspected EVD were diagnosed as EVD, there is need for better screening to optimise resource utilization and infection control.\n\nIn conclusion, notwithstanding the limitations of this study and the relatively small size of the 2020 outbreak, decentralized models of care offer an opportunity to potentially reduce community transmission of EVD and improve access to care for all diseases, especially in remote and hard-to-reach areas.\n\nEthical approval with waiver of informed consent was obtained from (a) National Ethics Committee of the School of Public Health, University of Kinshasa, DRC (Approbation Number: ESP/CE/115/2023 dated 04 August 2023), (b) Médecins Sans Frontières Operational Center Brussels Ethics Review Board (24 July 2023) and (c) Union Ethics Advisory Group, International Union against Tuberculosis and Lung Disease, Paris, France (EAG Number: 17/2023 dated 08 September 2023). Permission to access the line-list data was obtained from the MOH of the DRC.\n\nThis reporting of this study followed the STROBE guidelines.\n\nRepository: STROBE checklist for ‘Evaluation of centralised and decentralised models of care during the 2020 Ebola Virus Disease outbreak in Equateur Province, Democratic Republic of the Congo: A brief report’. 10.6084/m9.figshare.25983145.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nOpen access statement\n\nIn accordance with WHO’s open-access publication policy for all work funded by WHO or authored/co-authored by WHO staff members, WHO retains the copyright of this publication through a Creative Commons Attribution IGO license (http://creativecommons.org/licenses/by/3.0/igo/legalcode) which permits unrestricted use, distribution and reproduction in any medium provided the original work is properly cited.\n\n\nDisclaimer\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.",
"appendix": "Data availability\n\nFigshare: Evaluation of centralized and decentralized models of care during the 2020 Ebola Virus Disease outbreak in Equateur Province, Democratic Republic of the Congo: A brief report. https://doi.org/10.6084/m9.figshare.25634556. 26\n\nThe project contains the following underlying data:\n\n“Finaldataset F1000.xlsx” (Anonymised line-list of patients with suspected Ebola Virus Disease during the 2020 2020 Ebola Virus Disease outbreak in Equateur Province, Democratic Republic of the Congo).\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 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, Nairobi, Kenya; All India Institute of Medical Sciences, Hyderabad, India; and the National Training and Research Centre in Rural Health, Maferinyah, Guinea. We acknowledge the support of the Ministry of Health of the Democratic Republic of the Congo and appreciate the contribution of all the communities affected by EVD, the health workers and Aid partners. We are grateful to Bav Bavi Mayambula, GIS officer at Geographic Information System Centre, Médecins Sans Frontières, Belgium for developing the map of Democratic Republic of the Congo depicting the health zones and the EVD health facilities which has been used in this report.\n\n\nReferences\n\nEbola virus disease: [cited 2023 Jul 15]. Reference Source\n\nHampton LM, Luquero F, Costa A, et al.: Ebola outbreak detection and response since 2013. The Lancet Microbe. 2023 Sep 1; 4(9): e661–e662. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHistory of Ebola Disease Outbreaks|History|Ebola (Ebola Virus Disease)|CDC.2023 [cited 2024 Mar 25]. Reference Source\n\nVivalya BM, Ayodeji OA, Bafwa YT, et al.: Analysis of the management of the tenth Ebola virus disease outbreak in the Democratic Republic of Congo: developing a multidisciplinary response model to strengthen the healthcare system during disease outbreaks. Glob. Health. 2021 Oct 18; 17: 121. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGovernment of the Republic of Congo: Rapid Notes from the Integrated Ebola Analytic Cell: Evidence Review from Equateur 2020 (27 April 2022) - Democratic Republic of the Congo.2022 [cited 2024 Mar 25]. Reference Source\n\nCellule d’Analyse en Sciences Sociales: Analyses intégrées et multidisciplinaires en épidémie-Une revue des analyses intégrées menées durant les 90 premiers jours de l’épidémie d’Ebola en Equateur.2020 [cited 2024 Mar 25]. Reference Source\n\nMokuwa EY, Maat H: Rural populations exposed to Ebola Virus Disease respond positively to localised case handling: Evidence from Sierra Leone. PLoS Negl. Trop. Dis. 2020 Jan 21; 14(1): e0007666. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Bank: Overview.[cited 2024 Mar 26]. Reference Source\n\nCongo, Democratic Republic of the. The World Factbook. Central Intelligence Agency; 2024 [cited 2024 Mar 26]. Reference Source\n\nMinistère de la Santé Publique Secrétariat Général: Receuil des normes d’organisation et de fonctionnement des structures sanitaires de la zone de santé en RDC.2021.\n\nGovernment of Democratic Republic of Congo declares 11th Ebola virus disease outbreak. Africa CDC; [cited 2024 Mar 26]. Reference Source\n\nKinganda-Lusamaki E, Whitmer S, Lokilo-Lofiko E, et al.: 2020 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation. Lancet Microbe. 2024 Feb; 5(2): e109–e118. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCase definition recommendations for Ebola or Marburg virus diseases.[cited 2024 Apr 16]. Reference Source\n\nMédecins Sans Frontières (MSF) International: The Ebola response in the Democratic Republic of Congo. MSF; [cited 2023 Jun 20]. Reference Source\n\nMédecins Sans Frontières/Doctors Without Borders: Ensuring access to new treatments for Ebola virus disease.2023 [cited 2024 Mar 26]. Reference Source\n\nMinistere de la Sante, WHO Democratic Republic of the Congo: Strategic response plan for the Ebola virus disease outbreak May 2018: Democratic Republic of the Congo.2018 [cited 2023 Mar 25]. Reference Source\n\nBosa HK, Kamara N, Aragaw M, et al.: The west Africa Ebola virus disease outbreak: 10 years on. Lancet Glob. Health. 2024 Mar 22 [cited 2024 Mar 26]. Reference Source\n\nMbanzulu KM, Mboera LEG, Luzolo FK, et al.: Mosquito-borne viral diseases in the Democratic Republic of the Congo: a review. Parasit. Vectors. 2020 Feb 27; 13(1): 103. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMarks F, Im J, Park SE, et al.: Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study. Lancet Glob. Health. 2024 Apr; 12(4): e599–e610. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKayiba NK, Nitahara Y, Tshibangu-Kabamba E, et al.: Malaria infection among adults residing in a highly endemic region from the Democratic Republic of the Congo. Malar. J. 2024 Mar 18; 23(1): 82. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPlucinski MM, Guilavogui T, Sidikiba S, et al.: Effect of the Ebola-virus-disease epidemic on malaria case management in Guinea, 2014: a cross-sectional survey of health facilities. Lancet Infect. Dis. 2015 Sep 1; 15(9): 1017–1023. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWalker PGT, White MT, Griffin JT, et al.: Malaria morbidity and mortality in Ebola-affected countries caused by decreased health-care capacity, and the potential effect of mitigation strategies: a modelling analysis. Lancet Infect. Dis. 2015 Jul 1; 15(7): 825–832. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhan AS, Tshioko FK, Heymann DL, et al.: The Reemergence of Ebola Hemorrhagic Fever, Democratic Republic of the Congo, 1995. J. Infect. Dis. 1999 Feb 1; 179(Supplement_1): S76–S86. PubMed Abstract | Publisher Full Text\n\nRowe AK, Bertolli J, Khan AS, et al.: Clinical, Virologic, and Immunologic Follow-Up of Convalescent Ebola Hemorrhagic Fever Patients and Their Household Contacts, Kikwit, Democratic Republic of the Congo. J. Infect. Dis. 1999 Feb 1; 179(Supplement_1): S28–S35. PubMed Abstract | Publisher Full Text\n\nMulangu S, Dodd LE, Davey RT, et al.: A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N. Engl. J. Med. 2019 Dec 12; 381(24): 2293–2303. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLampaert E: Evaluation of centralized and decentralized models of care during the 2020 Ebola Virus Disease outbreak in Equateur Province, Democratic Republic of the Congo: A brief report. Figshare. [cited 2024 Apr 19]. Publisher Full Text"
}
|
[
{
"id": "304877",
"date": "02 Aug 2024",
"name": "Francesco Branda",
"expertise": [
"Reviewer Expertise My research interests are diverse",
"spanning various domains such as data analytics",
"epidemic intelligence systems",
"and public health risk studies. To address these questions",
"I developed novel methods that combine techniques from mathematical modelling",
"and statistical inference (including AI and Machine Learning). My work focuses to epidemiological and statistical consulting in hospital settings",
"applying statistical and molecular methods in clinical settings",
"and analyzing climate-sensitive diseases like Dengue and Chikungunya and outbreaks and pandemics such as SARS-CoV-2",
"Mpox",
"and Ebola."
],
"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\nSummary: This brief report evaluates centralized and decentralized models of care during the 2020 Ebola virus disease (EVD) outbreak in Equateur Province, Democratic Republic of Congo. The study compared the time from symptom onset to admission and diagnosis of patients with suspected EVD at centralized Ebola treatment centers (ETCs) versus decentralized treatment centers (DTCs) experienced during the outbreak. The main results were:\n1. 15% of patients with suspected EVD were admitted to a DTC for the first time. 2. The time to admission and diagnosis was significantly shorter for patients admitted to DTCs for the first time compared to CTEs. 3. Only 3% of all patients with suspected EVD were confirmed to have EVD. 4. There were no deaths from EVD in CDIs, compared with 12 deaths in CTEs.\nThe authors conclude that decentralized care models can help reduce community transmission and improve access to care, especially in remote areas, although further research is needed given the small size of the outbreak.\nEvaluation: 1. Is the study design appropriate and is the work technically sound? Yes, the cohort study design using secondary analysis of clinical data is appropriate for the research questions. The statistical methods used are sound.\n2. Are the methods and analyses detailed enough to allow replication by others? In part. More detail could be provided on: - Specific criteria used to designate a facility as an ETC or DTC. - Process for creating DTCs (e.g., how existing facilities were selected/equipped). - Data cleaning and quality control procedures for the list of data lines. - Handling of missing data\n3. If data is available, is the source and origin of the data clearly indicated? Yes, the source of the data (list of MOH lines) is clearly indicated and a link to the anonymized dataset is provided.\n4. Are the conclusions drawn adequately supported by the results? In part. The conclusions are generally supported, but some caveats could be stated more explicitly: - The small number of confirmed EVD cases limits conclusions about outcomes. - Potential confounding factors not taken into account (e.g., disease severity, geographic proximity). - Lack of qualitative data on patients' and providers' perspectives.\n5. Is the article comprehensibly presented and written in standard English? Yes, the article is well written and clearly presented.\n\nRecommendations for improvement:\n1. Provide more methodological details as indicated above to improve reproducibility.\n2. Expand discussion of limitations, particularly regarding the small number of confirmed cases and potential confounding factors.\n3. Include, if possible, a brief qualitative component (e.g., interviews with health care providers) to provide context on the implementation of the DTC model.\n4. Clarify whether sensitivity analyses were conducted to assess the impact of missing data.\n5. Consider adding a figure showing the time trend of DTC establishment and number of cases to illustrate the phase-in.\n6. Provide more detail on deaths in the community that occurred outside of facilities, if available, to put the results in context.\n7. Discuss more explicitly in the conclusions the implications and recommendations for future outbreaks.\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? 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? Partly",
"responses": [
{
"c_id": "12275",
"date": "28 Aug 2024",
"name": "Divya Nair",
"role": "Author Response",
"response": "We thank the esteemed reviewer for the recommendations for improvement. We would like to mention that this article is submitted under the ‘Brief Report’ category of the journal, and has a word limit restriction of 2500 words. Therefore, we have tried to address the concerns to the best of our ability within the constraints of the word limits. Provide more methodological details as indicated above to improve reproducibility. More detail could be provided on: Specific criteria used to designate a facility as an ETC or DTC. Response: As mentioned in the manuscript, the approach of decentralisation was piloted for the first time in the Equateur province. The decision on designation of a facility as an ETC or DTC was made empirically by the outbreak response team led by the MoH in consultation with the various aid partners. While there was no standard guideline document for these decisions, the following were the considerations. We have now added a row in Table 1 explaining these. Process for creating DTCs (e.g., how existing facilities were selected/equipped). Response: The main considerations for selecting DTCs is outlined in the revised Table 1. Once a facility was selected to function as a DTC, the outbreak response team demarcated a triage area and an isolation area, ensured supply of basic personal protective equipment and apparatus required for sample collection-transport and for providing supportive treatment for suspected cases were available and established a biomedical waste management system, including identification of safe burial spaces in consultation with the local community. These have been enumerated in the revised version of the manuscript under the “Specific setting” section. Data cleaning and quality control procedures for the list of data lines.Response: During the outbreak, the MSF team (under directions of the MOH) developed a common form to collect the basic details of patients admitted as suspected cases to any EVD health facility. A healthcare worker was identified as a focal person in each facility and was responsible for data collection and updation of the form on a daily basis. This person was responsible for ensuring the quality and completeness of the data. MSF supervisors were responsible for electronic entry from paper forms on to an MS Excel file, known as the ‘Common linelist’. At the time of digitization, the supervisor would check for data completeness and whenever possible coordinate with the facility focal person to retrieve missing data from the facility treatment records and update the linelist. During the outbreak, this linelist was used primarily to know the occupancy rate of facilities and the vaccination status of suspected cases and these variables were the focus of quality control processes during the outbreak. We have included a brief description of this process in the revised version of the manuscript in the ‘Data collection, sources, and analysis’ section. We have also highlighted the quality issues and the need for good quality data in Discussion section. Handling of missing data. Response: The number of observations with missing data are reported for key variables. Since the outcome variables (time to diagnosis and time to admission) were non-parametric, imputation techniques and sensitivity analysis to assess impact of missingness in these variables were not performed. Statistical tests were performed after omitting the observations with missing data for the outcome variables pertaining to the test. This has been added under the “Data collection, sources, and analysis” section of the revised manuscript Expand discussion of limitations, particularly regarding the small number of confirmed cases and potential confounding factors. The conclusions are generally supported, but some caveats could be stated more explicitly: The small number of confirmed EVD cases limits conclusions about outcomes. Potential confounding factors not taken into account (e.g., disease severity, geographic proximity). Lack of qualitative data on patients' and providers' perspectives.Response: We agree with this suggestion and have tried to bring in the limitations in the “Conclusion” paragraph. Include, if possible, a brief qualitative component (e.g., interviews with health care providers) to provide context on the implementation of the DTC model. Response: We agree that a qualitative component would have added value to this assessment. However, we are unable to conduct a qualitative inquiry at present because: (1) Since the outbreak in 2020, there have been massive staff turnovers and the relevant health care workers are no longer available in health zones which can be accessed by the principal investigator. (2) There is an ongoing political unrest and a Monkey Pox outbreak in the DRC which has led to diversion of human resources to conflict zones and MPox response. The principal investigator himself and the co-authors from DRC are involved in the response and shall not be able to conduct the qualitative interviews (seek ethical approvals, trace and interview the healthcare workers, analyse data).We have therefore cited this as a limitation. Also, we have referenced and cites a situational analysis of the first 90 days of the outbreak conducted by UNICEF (Reference 6), which provides some qualitative insights into the communities’ non-acceptance for ETCs and makes recommendations for decentralised care provision. Clarify whether sensitivity analyses were conducted to assess the impact of missing data. Response: In this study, the key outcomes of interest which has missing data were time to diagnosis and time to admission. Both these variables were found to be non-parametric. To do a sensitivity analysis, we would need to use an imputation technique. We could apply a non-parametric imputation technique (hot-deck/ predictive mean matching) to generate their imputed values but we are unaware of any robust statistical package which would allow us to perform a Mann-Whitney test on the multiply imputed data sets. Therefore, we have refrained from using any imputation techniques in this study Consider adding a figure showing the time trend of DTC establishment and number of cases to illustrate the phase-in. Response: We have now provided a figure titled “Graph showing the time trend of confirmed cases and the establishment of Centralised Ebola treatment centre (ETC) and Decentralised treatment centre (DTC) in Equateur Province, Democratic Republic of Congo during the 2020 outbreak of Ebola Virus disease” as Figure 2. Provide more detail on deaths in the community that occurred outside of facilities, if available, to put the results in context. Response: We are unable to provide any more detail on deaths that occurred outside of facilities, apart from what is already stated in the manuscript. These deaths were retrospectively classified as Ebola deaths because of identified epidemiological links with confirmed cases of EVD. The reason for delayed notification of deaths and subsequent investigations could possibly be due to the occurrence of EVD cases in remote health zones in Northern parts of the province, which had no experience with EVD outbreaks in the past. However, this is speculative and we are unable to substantiate this with available data. Discuss more explicitly in the conclusions the implications and recommendations for future outbreaks. Response: We have tried to expand the conclusion with inclusion of limitations and recommendations."
}
]
},
{
"id": "304876",
"date": "06 Aug 2024",
"name": "Nlandu Roger Ngatu",
"expertise": [
"Reviewer Expertise Environmental and occupational health",
"Global health",
"Infectious 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 authors compared time from the onset of EVD symptoms to admission and diagnosis in suspected EVD patients between ETCs and DTCs in a retrospective cohort study conducted in D.R. Congo. They found that the duration between onset of EVD symptoms and admission was significantly lower in suspected patients admitted at DTCs compared to those admitted in ETCs. The manuscript is well written, and data are well presented. I have a few comments in relation to the methodology. 1. Study design: authors analyzed existing data from the outbreak that occurred in Equateur, D.R. Congo, in 2020. They should mention it as being a Retrospective cohort study. 2. Data collection, sources and analysis:\n\n- Authors should specify the outcome variable(s)\n\nused in this study. - Authors stated that they used Stata software to analyze the data. They also mention R software. So, I wonder why \"R\" after using Stata? What was the purpose of using R software?\nI would be glad if authors can provide answers to the two comments.\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": "12276",
"date": "28 Aug 2024",
"name": "Divya Nair",
"role": "Author Response",
"response": "We thank the esteemed reviewer for the comments. The following are responses to the two comments, as requested: 1. Study design: authors analysed existing data from the outbreak that occurred in Equateur, D.R. Congo, in 2020. They should mention it as being a Retrospective cohort study. Response: We agree and have changed the design to “Retrospective cohort study” in “Study design” section of the revised manuscript. 2. Data collection, sources and analysis: - Authors should specify the outcome variable(s) used in this study. - Authors stated that they used Stata software to analyse the data. They also mention R software. So, I wonder why \"R\" after using Stata? What was the purpose of using R software? Response: Thank you for the suggestion. We have listed the outcome variables in “Data collection, sources, and analysis” section of the revised manuscript. Regarding R software, the F1000 Open Data, Software and Code Guidelines website (https://f1000research.com/for-authors/data-guidelines), mention that “Where third-party proprietary software has been used, a non-proprietary, Open Source alternative software should be suggested by the author to allow for the replication of the analysis or research by all readers”. Therefore, we have mentioned that “R is an open-access software which can be used to perform the same analysis” as an alternative to the proprietary software (Stata) that we used. Since this was a journal requirement, we would like to retain the statement in the manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/13-642
|
https://f1000research.com/articles/13-251/v1
|
04 Apr 24
|
{
"type": "Genome Note",
"title": "A reference genome, mitochondrial genome and associated transcriptomes for the critically endangered swift parrot (Lathamus discolor)",
"authors": [
"Luke W. Silver",
"Dejan Stojanovic",
"Katherine A. Farquharson",
"Lauren Alexander",
"Emma Peel",
"Katherine Belov",
"Carolyn J. Hogg",
"Luke W. Silver",
"Dejan Stojanovic",
"Katherine A. Farquharson",
"Lauren Alexander",
"Emma Peel",
"Katherine Belov"
],
"abstract": "Abstract* The swift parrot (Lathamus discolor) is a Critically Endangered migratory parrot that breeds in Tasmania and winters on the Australian mainland. Here we provide a reference genome assembly for the swift parrot. We sequence PacBio HiFi reads to create a high-quality reference assembly and identify a complete mitochondrial sequence. We also generate a reference transcriptome from five organs to inform genome annotation. The genome was 1.24 Gb in length and consisted of 847 contigs with a contig N50 of 18.97 Gb and L50 of 20 contigs. This study provides an annotated reference assembly and transcriptomic resources for the swift parrot to assist in future conservation genomic research.",
"keywords": [
"Genome assembly",
"reference genome",
"transcriptome",
"Aves",
"mitogenome"
],
"content": "Introduction\n\nThe swift parrot (Lathamus discolor) is a migratory parrot that breeds on the island of Tasmania, Australia and winters on mainland Australia (Kennedy & Tzaros, 2005; MacNally & Horrocks, 2000; Saunders & Heinsohn, 2008). The swift parrot is Critically Endangered (BirdLife International, 2018) due to the combined effects of logging of its important breeding habitat (Webb et al., 2019) and the impacts of an introduced predator (Heinsohn et al., 2015). Population viability analysis has shown that the already small population of only a few hundred swift parrots (Olah et al., 2021) is likely to rapidly decline over coming generations (Heinsohn et al., 2015; Owens et al., 2023) Although the species has already been subject to population genetic study (Olah et al., 2021; Stojanovic et al., 2018), there remain outstanding questions about multiple aspects of the species’ genetic ecology. For example, like other parrots with small population sizes (Morrison et al., 2020), understanding the genetic basis of immune competence is critical for managing demographic impacts of disease in swift parrots (Saunders & Tzaros, 2011). To facilitate detailed genomic research on this species, we sequenced DNA with PacBio long reads to generate a high-quality reference assembly and sequenced RNA from five tissues to provide transcriptomic resources and assist in genome annotation for the swift parrot.\n\n\nMethods\n\nA single captive bred female swift parrot died as a result of liver infection. Tissue samples were dissected and flash frozen at -80°C or preserved in RNAlater before being frozen at -80°C. High molecular weight (HMW) DNA was then extracted from heart and kidney tissue using the Nanobind Tissue Big DNA Kit v1.0 (Circulomics: SKU 102-302-100) using the standard protocol. A Qubit fluorometer was used to assess the concentration of DNA with the Qubit dsDNA BR assay kit (Thermo Fisher Scientific). Total RNA was extracted from gonad, spleen, liver, heart and kidney using the RNeasy Plus Mini Kit (Qiagen: 74134) with RNAse-free DNAse I set (Qiagen: EN0521) using the standard protocol. RNA quality was determined using the NanoDrop (Thermo Fisher Scientific) and RNA integrity (RIN) score determined using the Bioanalyzer RNA nano 6000 kit (Agilent 2100: 5067-1511).\n\nHMW DNA was sent for Pacific Biosciences High Fidelity (PacBio HiFi) library preparation with the SMRTbell Express Template Prep Kit 2.0 (Pacific Biosciences: 101-853-100) and sequencing on one single molecule real-time (SMRT) cell of the PacBio Sequel II at the Australian Genome Research Facility (St Lucia, Australia). Total RNA from the heart, gonad, kidney, liver and spleen was sequenced as 100 bp paired-end (PE) reads using an Illumina Novaseq 6000 with Illumina Stranded mRNA library preparation at the Ramaciotti Centre for Genomics (University of New South Wales, Kensington, Australia).\n\nThe genome assembly was conducted on the Galaxy Australia public server usegalaxy.org.au (Afgan et al., 2016) running the Genome assembly with ‘hifiasm’ (RRID:SCR_021069) (Cheng et al., 2022) on Galaxy Australia workflow v2.1 (Price & Farquharson, 2022). Briefly, Picard (http://broad institute.github.io/picard) (Galaxy version 2.18.2.2; RRID:SCR_006525) SamToFastq, samtools (Danecek et al., 2021; Li et al., 2009) (Galaxy version 2.0.3; RRID:SCR_002105) flagstat and fastQC (https://www.bioinformatics.babraham.ac.uk/projects/fastqc/) (Galaxy version 0.72; RRID:SCR_014583) was used to convert BAM files to FASTQ and quality check the reads for input to Hifiasm (Cheng et al., 2022). Hifiasm (Galaxy version 2.1) was run on Galaxy Australia to assembly the genome. Basic genome assembly statistics were calculated with the stats.sh script in BBMap (sourceforge.net/projects/bbmap/) (RRID:SCR_016965). Genome completeness was determined using Benchmarking Universal Single-Copy Orthologues (BUSCO; RRID:SCR_015008) v5.4.6 (Simao et al., 2015) with the vertebrata_odb10 (n = 3354) and aves_odb10 (n= 8338) lineage on Galaxy Australia. Repetitive elements of the genome were identified, classified and masked using a Pawsey Supercomputing Centre Nimbus cloud machine (256GB RAM, 64 vCPU, 3 TB storage) by building a database using RepeatModeler v2.0.1 (RRID:SCR_015027) (Flynn et al., 2020); repeats were then masked using RepeatMasker v4.0.9 (RRID:SCR_012954) (Smit et al., 2013-2015) with the -nolow parameter to avoid masking low complexity repeats.\n\nThe mitochondrial genome was identified from the reference genome assembly using MitoHiFi v2 (Allio et al., 2020; Uliano-Silva et al., 2023) and visualised using Proksee (Grant et al., 2023). MitoHifi identified the most taxonomically closely related publicly available mitochondrial genome, the thick-billed parrot (Rhynchopsitta pachyrhyncha) (NCBI reference sequence OR209192.1), used to search for the swift parrot mitochondrial genome.\n\nTranscriptome assembly was performed on the University of Sydney High Performance Computer, Artemis. Raw transcriptome reads were quality assessed pre and post trimming with FastQC v0.11.8 (RRID:SCR_014583). Trimmomatic v0.39 (RRID:SCR_011848) (Bolger et al., 2014) with the parameters SLIDINGWINDOW:4:5, LEADING:5, TRAILING:5 and MINLEN:25 and ILLUMINACLIP:2:30:10 with the TruSeq3-PE adapters was used to quality trim reads. The repeat masked genome was indexed and trimmed reads aligned using the -dta parameter with hisat2 v2.1.0 (RRID:SCR_015530) (Kim et al., 2019). Resulting sam files with converted to bam format and sorted using samtools v1.9 (Danecek et al., 2021). Stringtie v2.1.6 (RRID:SCR_016323) (Pertea et al., 2015) was used to generate a GTF for each transcriptome. Stringtie v2.1.6 with the -merge parameter merged transcripts into a global transcriptome retaining only transcripts with an FPKM > 0.1 and length > 30. CPC2 v2019-11-19 (Kang et al., 2017) was used to predict coding potential and only transcripts predicted to be coding were retained. Transdecoder v2.0.1 (https://github.com/TransDecoder/TransDecoder) (RRID:SCR_017647) was used to predict open reading frames in the global transcriptome with a minimum transcript length of 20. Transcriptome completeness was assessed using BUSCO v5.4.6 (Simao et al., 2015) with the vertebrata_odb10 (n = 3354) and aves_odb10 (n = 8338) lineage on Galaxy Australia.\n\nGenome annotation was performed using FGENESH++ v7.2.2 (Softberry; RRID:SCR_018928 (Solovyev et al., 2006)) using the longest open reading frame as predicted from the global transcriptome, non-mammalian settings and optimised parameters supplied with the American crow (Corvus brachyrhynchos) gene finding matrix. BUSCO v5.4.6 (Simao et al., 2015) in protein mode was run on Galaxy Australia to assess the completeness of the annotation with the vertebrata_odb10 (n = 3354) and aves_odb10 (n = 8338) lineage. The ‘genestats’ script (https://github.com/darencard/GenomeAnnotation) was used to obtain the average number of exons and introns and the average exon and intron length.\n\n\nResults\n\nGenome assembly using Hifiasm with PacBio HiFi data from a single SMRT cell resulted in a coverage of 28.7x and a genome of 1.24 Gb in size consisting of 847 contigs with a contig N50 of 18.97 Mb and L50 of 20 contigs. The genome assembly was also highly complete with 97.0% of aves_odb10 complete BUSCOs identified (Table 1). The mitochondrial genome was 19,498 bp long and contained 38 genes, including 25 tRNAs and 13 protein coding genes, with a GC percentage of 44.59% (Figure 1).\n\nTrimming retained greater than 99.95% of raw reads which were then aligned to the repeat-masked reference genome. Individual tissue transcriptomes had variable mapping rates from 31.04% for heart tissue to 82.76% for gonad tissue (kidney: 62.26%, liver: 78.84%, spleen: 73.60%). The alignment rate for the heart tissue was low so we excluded heart transcripts from downstream analysis. The poor performance of the heart tissue is potentially due to the comparatively lower concentration of RNA in the heart tissue extraction (35.2 ng/μl) compared to the other 4 tissues (average = 1243 ng/μl [SD: 481]) and the heart tissue was not stored in RNAlater. After using stringtie -merge to generate a global transcriptome and filtering on coding potential and open reading frames with CPC2 and transdecoder, respectively, 14,045 longest open reading frame transcripts were used as mRNA evidence to guide genome annotation. The global transcriptome had 90.8% complete aves_odb10 BUSCOs (Table 2). A total of 27,867 genes were predicted from genome annotation, higher than the predicted 15,000-16,000 genes in birds (Zhang et al., 2014). The annotation contained 78.1% complete aves_odb10 BUSCOs (Table 2). Repetitive elements comprised 17.25% of the genome, mainly consisting of long interspersed elements (LINEs), comparable with other bird genomes (Zhang et al., 2014) (Table 3).\n\nThe sample used for genome and transcriptome sequencing was obtained from an individual who died of natural causes.",
"appendix": "Data availability\n\nThe raw PacBio HiFi and transcriptome data are publicly available through the Bioplatforms Australia Threatened Species Initiative: https://data.bioplatforms.com/organization/threatened-species . The assembled genome, global transcriptome and annotation generated in this study are available on Amazon Web Services Australasian Genomes Open Data Store: https://awgg-lab.github.io/australasiangenomes/genomes.html.\n\nRaw genome and transcriptome sequences are also available from NCBI’s Short Read Archive (SRA) accession numbers SRR26186073 to SRR26186078 (Silver et al., 2023).\n\nAnd the assembled genome from NCBI’s Assembly database, BioProject: PRJNA1021263 (Silver et al., 2023).\n\nFigshare: Author Checklist - ARRIVE.pdf, https://doi.org/10.6084/m9.figshare.25396294.\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\nThanks to Bonorong Wildlife Sanctuary and the Department of Natural Resources and Environment Tasmania for facilitating access to genetic samples. Computational resources were provided by the Australian FGENESH++ Service provided by the Australian BioCommons and the Pawsey Supercomputing Research Centre with funding from the Australian Government and the Government of Western Australia; Galaxy Australia, a service provided by the Australian Biocommons and its partners; and the University of Sydney’s High Performance Computing facility Artemis provided by the Sydney Informatics Hub. The authors wish to acknowledge the use of the services and facilities of the Ramaciotti Centre for Genomics, UNSW and of the Australian Genome Research Facility.\n\n\nReferences\n\nAfgan E, Baker D, van den Beek M , et al.: The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update. Nucleic Acids Res. 2016; 44(W1): W3–W10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAllio R, Schomaker-Bastos A, Romiguier J, et al.: MitoFinder: Efficient automated large-scale extraction of mitogenomic data in target enrichment phylogenomics. Mol. Ecol. Resour. 2020; 20(4): 892–905. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBirdLife International: Lathamus discolor. The IUCN Red List of Threatened Species 2018.2018. Publisher Full Text\n\nBolger AM, Lohse M, Usadel B: Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014; 30(15): 2114–2120. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCheng H, Jarvis ED, Fedrigo O, et al.: Haplotype-resolved assembly of diploid genomes without parental data. Nat. Biotechnol. 2022; 40(9): 1332–1335. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDanecek P, Bonfield JK, Liddle J, et al.: Twelve years of SAMtools and BCFtools. Gigascience. 2021; 10(2). PubMed Abstract | Publisher Full Text | Free Full Text\n\nFlynn JM, Hubley R, Goubert C, et al.: RepeatModeler2 for automated genomic discovery of transposable element families. Proc. Natl. Acad. Sci. USA. 2020; 117(17): 9451–9457. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGrant JR, Enns E, Marinier E, et al.: Proksee: in-depth characterization and visualization of bacterial genomes. Nucleic Acids Res. 2023; 51(W1): W484–W492. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHeinsohn R, Webb M, Lacy R, et al.: A severe predator-induced population decline predicted for endangered, migratory swift parrots (Lathamus discolor). Biol. Conserv. 2015; 186: 75–82. Publisher Full Text\n\nKang YJ, Yang DC, Kong L, et al.: CPC2: a fast and accurate coding potential calculator based on sequence intrinsic features. Nucleic Acids Res. 2017; 45(W1): W12–W16. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKennedy SJ, Tzaros CL: Foraging ecology of the swift parrot Lathamus discolor in the box-ironbark forests and woodlands of Victoria. Pac. Conserv. Biol. 2005; 11(3): 158–173. Publisher Full Text\n\nKim D, Paggi JM, Park C, et al.: Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 2019; 37(8): 907–915. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi H, Handsaker B, Wysoker A, et al.: The sequence alignment/map format and SAMtools. Bioinformatics. 2009; 25(16): 2078–2079. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMacNally R, Horrocks G: Landscape-scale conservation of an endangered migrant:the swift parrot (Lathamus discolor) in its winter range. Biol. Conserv. 2000; 92(3): 335–343. Publisher Full Text\n\nMorrison CE, Hogg CJ, Gales R, et al.: Low innate immune-gene diversity in the critically endangered orange-bellied parrot (Neophema chrysogaster). Emu Austral Ornithol. 2020; 120(1): 56–64. Publisher Full Text\n\nOlah G, Stojanovic D, Webb MH, et al.: Comparison of three techniques for genetic estimation of effective population size in a critically endangered parrot. Anim. Conserv. 2021; 24(3): 491–498. Publisher Full Text\n\nOwens G, Heinsohn R, Crates R, et al.: Long-term ecological data confirm and refine conservation assessment of critically endangered swift parrots. Anim. Conserv. 2023; 26(4): 450–463. Publisher Full Text\n\nPertea M, Pertea GM, Antonescu CM, et al.: StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat. Biotechnol. 2015; 33(3): 290–295. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPrice G, Farquharson K: PacBio HiFi genome assembly using hifiasm v2.1. WorkflowHub. 2022. Publisher Full Text\n\nSaunders DL, Heinsohn R: Winter habitat use by the endangered, migratory swift parrot (Lathamus discolor) in New South Wales. Emu Austral Ornithol. 2008; 108(1): 81–89. Publisher Full Text\n\nSaunders DL, Tzaros CL: National recovery plan for the swift parrot Lathamus discolor. Melbourne: Birds Australia; 2011.\n\nSilver LW, Stojanovic D, Farquharson K, et al.: Lathamus discolor Genome sequencing and assembly.2023. Reference Source\n\nSimao FA, Waterhouse RM, Ioannidis P, et al.: BUSCO: Assessing genome assembly and annotation completeness with single-copy orthologs. Bioinformatics. 2015; 31(19): 3210–3212. Publisher Full Text\n\nSmit A, Hubley R, Green P: RepeatMasker Open-4.0.2013-2015.\n\nSolovyev V, Kosarev P, Seledsov I, et al.: Automatic annotation of eukaryotic genes, pseudogenes and promoters. Genome Biol. 2006; 7 Suppl 1(Suppl 1): S10.1–S1012. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStojanovic D, Olah G, Webb M, et al.: Genetic evidence confirms severe extinction risk for critically endangered swift parrots: Implications for conservation management. Anim. Conserv. 2018; 21(4): 313–323. Publisher Full Text\n\nUliano-Silva M, Ferreira JGRN, Krasheninnikova K, et al.: MitoHiFi: a python pipeline for mitochondrial genome assembly from PacBio High Fidelity reads. bioRxiv. 2023. 2022.2012.2023.521667. Publisher Full Text\n\nWebb MH, Stojanovic D, Heinsohn R: Policy failure and conservation paralysis for the critically endangered swift parrot. Pac. Conserv. Biol. 2019; 25(2): 116–123. Publisher Full Text\n\nZhang G, Li C, Li Q, et al.: Comparative genomics reveals insights into avian genome evolution and adaptation. Science. 2014; 346(6215): 1311–1320. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "274647",
"date": "04 Jun 2024",
"name": "Charles Feigin",
"expertise": [
"Reviewer Expertise Evolutionary Biology",
"Developmental Biology",
"Genomics",
"Marsupials"
],
"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\nHere, the authors present a short report detailing the production of nuclear and mitochondrial genome assemblies for the swift parrot Lathamus discolor, together with annotations supported by multi-tissue transcriptomes. The swift parrot is a Critically Endangered species and the target of conservation efforts, making these new data and resources valuable. Overall, the report is well written, and I appreciated the very detailed methods sections with parameters spelled out. I had one notable comment related to data availability and sequence length of the mitochondrial genome assembly. Further comments are fairly minor given the straightforward nature of the genome report.\nData availability and length discrepancy of the mitochondrial genome assembly - While other data in the paper has been made readily available and are associated with the BioProject on NCBI (or on FigShare or the AWS database), it is unclear whether the mitochondrial assembly has been made available. I found that the genome assembly itself on NCBI contains a contig that has been labelled as the mitochondrial genome, JAXCIO010000845.1. However, the length of this sequence (17,265 bp) differs substantially from the mitochondrial genome length reported in the paper (19,498 bp). Is this the same mito assembly described in the paper, or was this contig produced during the de novo assembly of the nuclear genome? I note that the ~17 kbp sequence included in your genome file is more typical for the length of vertebrate mitochondria and is much closer in size to the related parrot you indicated in the paper (Rhynchopsitta pachyrhyncha, OR209192.1) than the ~19kb produced by MitoHifi v2 and reported in-text. I request the following:\nIf the mitochondrial contig JAXCIO010000845.1 included in the assembly file is the same mitochondrial assembly described in the report, then the length discrepancy between this contig and what is reported in the paper needs to be addressed. If JAXCIO010000845.1 is not the same as the mito assembly reported in the paper, then 1) your de novo ~19kb mitochondrial genome needs to be deposited into Genbank and associated with your BioProject and 2) the length discrepancy between these two should still be addressed,\n\"and the impacts of an introduced predator\" - it is probably worth spelling out what the predator is.\n\"to generate a high-quality reference assembly\" - . Chromosome-level de novo genome assemblies have become standard, even for vertebrates, and are very slowly starting to be superseded by T2T assemblies. Given current standards and the recent VGP L. discolor reference genome, the assembly presented here would best be described a draft assembly throughout.\nGenome assembly methods - What Hifiasm parameters were used? If default that's fine, just note it.\nTable 3 \"DNA elements\" - The label \"DNA elements\" is default for RepeatMasker but its a fairly vague label for these elements. It would be helpful to rephrase this as \"DNA Transposons\" to be more specific/clear about what they are.\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? No",
"responses": [
{
"c_id": "12255",
"date": "27 Aug 2024",
"name": "Luke Silver",
"role": "Author Response",
"response": "The mitochondrial contig listed on NCBI is the correct mitochondrial assembly, it appears that MitoHifi annotates the entire contig which was identified to contain mitochondrial genome even if it is much larger than the expected size. I had replaced the identified contig with only the portion of sequence which represented the mito genome in the assembly file, however not the data which was used to annotate and produce figure 1. I have edited and updated the manuscript to reflect the changes. “The mitochondrial reference sequence for the thick-billed parrot was then, used to search for the swift parrot mitochondrial genome. The identified mitochondrial sequence was then added to the genome assembly and annotated using MITOS v 2.1.7 (Donath et al., 2019) and visualised using Proksee ( Grant et al., 2023).” I have edited the sentence to name the predator “… and the impacts of an introduced predator, the sugar glider (Petaurus breviceps) I have replaced high-quality with draft when referring to the genome assembly throughout I have stated that hifiasm was run with default parameters, “Hifiasm, with default parameters, was run on Galaxy Australia…” I have relabelled DNA elements as DNA transposons in Table 3"
}
]
},
{
"id": "296521",
"date": "13 Jul 2024",
"name": "Phred Benham",
"expertise": [
"Reviewer Expertise genomics",
"ornithology",
"evolution"
],
"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 de novo assembly of the critically endangered swift parrot. Generally the sequencing and assembly methods reflect current standards and they produce a highly contiguous, contig-level assembly for this species that will be of value for various conservation genomics and other molecular ecology questions. I have only a few minor comments.\nIs there a reason you did not attempt to produce a scaffolded assembly?\nIf there is space it would be nice to have a figure(s) showing the parrot, distribution, etc.\nI agree with the other reviewer that this assembly is larger than the typical avian mito-genome and worth confirming there is not spurious sequence included.\nWas a voucher specimen preserved of the parrot that died?\n\nThe last sentence of the 'mitochondrial assembly' section is not clearly written, please revise.\nResulting sam files 'were' not 'with' converted...\nWhy did you use crow for the gene finding matrix. Were there not other parrots or something more closely related?\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": [
{
"c_id": "12256",
"date": "27 Aug 2024",
"name": "Luke Silver",
"role": "Author Response",
"response": "We did not attempt a scaffolded assembly as for conservation and population genetics work we have found a long read assembly to be sufficient, additionally after we produced our long read assembly a chromosome level scaffolded assembly was released by VGP. In lieu of adding in an additional figure showing the distribution of the swift parrot, we have added some additional detail as to the regions where swift parrots breed and migrate to “The swift parrot ( Lathamus discolor) is a migratory parrot that breeds on the eastern seaboard of the island of Tasmania, Australia and winters on southeastern mainland Australia” As requested by the other reviewer I have ensured the mitochondrial information included in the manuscript and online is correct and updated to reflect this. The individual used for the genome and transcriptome will be accessioned into a museum collection by the end of 2024, when this has been completed the BioProject information on NCBI will be updated to provide the accession number I have rephrased this to make sense. “…genome as, the thick-billed parrot ( Rhynchopsitta pachyrhyncha) (NCBI reference sequence OR209192.1). The mitochondrial reference sequence for the thick-billed parrot was then, used…” I have changed with to were The crow is the most closely related species with a matrix provided by FGENESH, I have edited the methods to reflect this. “…gene finding matrix, which is the closest related species with a gene finding matrix provided by FGENESH++”"
}
]
}
] | 1
|
https://f1000research.com/articles/13-251
|
https://f1000research.com/articles/13-970/v1
|
27 Aug 24
|
{
"type": "Case Report",
"title": "Case Report: Managing Odontoma and Molar-Incisor-Hypomineralization Challenges in Orthodontics",
"authors": [
"Nora Alhazmi",
"Khalid Albawardi",
"May Aleraij",
"Maram A. Alqahtani",
"Faisal O. Alsharif",
"Sohaib Shujaat",
"Khalid Albawardi",
"May Aleraij",
"Maram A. Alqahtani",
"Faisal O. Alsharif",
"Sohaib Shujaat"
],
"abstract": "This report presents the successful orthodontic management of a case of odontoma associated with impaction of the mandibular right permanent canine and Molar-incisor-hypomineralization (MIH). Although case studies have reported the management of odontomas and MIH as separate entities, there is a lack of evidence regarding the comprehensive management of patients presenting with a combination of odontoma, dental impaction, and MIH. A 15-year, 7-month-old female patient complained of the appearance of her smile and the delayed eruption of her mandibular right permanent canine. She was diagnosed with Angle’s Class I molar relationship and Class II canine relationship with the maxillary permanent right lateral incisor in a lingual crossbite. Furthermore, she had mandibular right permanent canine impaction, retained mandibular right primary canine, and MIH in the permanent anterior teeth and first molars. The management involved the removal of the odontoma to allow for orthodontic traction of the lower permanent right canine. After that, the esthetic appearance of the teeth was improved through restorative treatment.",
"keywords": [
"orthodontic",
"hypomineralization",
"odontoma",
"impaction",
"case report"
],
"content": "1. Introduction\n\nOdontoma, a common odontogenic tumor, has a prevalence ranging from 21% to 67% among all oral tumors.1,2 These tumors can be classified into two types based on their morphological features: compound and complex.3 In compound odontomas, enamel and dentin are deposited in a way that the resulting structure resembles normal teeth. On the other hand, complex odontomas exhibit irregular masses of dental tissues. Compound odontomas are more frequent than complex ones. Approximately half of these abnormalities are associated with the impaction of permanent teeth, especially canines.4 The presence of odontoma can disrupt the eruption of permanent teeth, which not only compromises occlusal function and aesthetics but may also adversely affect adjacent teeth by causing root resorption.\n\nMoreover, MIH is a prevalent dental developmental disorder that affects approximately 10% to 20% of children and adolescents.5 MIH originates systemically and involves hypomineralization of one to four permanent first molars, often accompanied by affected incisors. The etiology of MIH remains elusive, but it is likely multifactorial, resulting from various environmental factors acting systemically, including prenatal, perinatal, and childhood medical conditions.5 Clinically, teeth affected by MIH exhibit distinct areas of enamel opacities with alterations in translucency, showing a wide variation in color, size, and shape. It can significantly impact a patient’s oral health-related quality of life, causing functional difficulties and aesthetic concerns.6 The best long-term solution involves a combination of minimally invasive treatment options, such as external bleaching, microabrasion, and resin infiltration. However, these treatments may interfere with orthodontic procedures, especially during the adhesion of fixed appliances.7 Additionally, hypomineralized enamel may not withstand forces during active orthodontic treatment or appliance debonding.8\n\nNumerous case studies have documented dental and orthodontic management of odontomas and molar-incisor-hypomineralization (MIH) as separate entities. However, there is a lack of evidence regarding the comprehensive management of patients presenting with a combination of odontoma, dental impaction, and MIH. From a clinical perspective, it is crucial for practitioners to be familiar with the comprehensive management of such cases to enhance treatment outcomes and current standards of care. Therefore, the aim of this case report was to present a multidisciplinary approach for managing a patient with a compound odontoma associated with an impacted mandibular canine and MIH.\n\n\n2. Etiology and diagnosis\n\nThis case report was conducted in compliance with the World Medical Association Declaration of Helsinki on medical research. Ethical approval was obtained from the Ethical Review Board of the University Hospital (NRR24/061/5). A written informed consent was obtained from the patient to publish the current case report and accompanying images. In addition, the Consensus-based Clinical Case Reporting Guideline Development (CARE) guidelines checklist was followed.9\n\nA 15-year and 7-month-old female patient presented to the orthodontic clinic at University Hospital. The main concern of the patient was the appearance of her smile, and she expressed worry about the delayed eruption of her mandibular right permanent canine. The patient had no history of trauma. Furthermore, the patient had iron deficiency anemia and vitamin D deficiency, and she irregularly took iron and vitamin D supplements. Patient also had a history of antibiotics administration for fever at the age of 2 years. During an investigation into teeth discoloration, the patient’s mother reported experiencing stress during pregnancy and had a history of urinary tract infection, which was treated with antibiotics. Additionally, the mother reported prolonged labor during childbirth.\n\nUpon extraoral examination, a convex profile with competent lips was observed in the lateral view. In the frontal view of the non-smiling face, a deviated nose and symmetrical features were evident. When smiling, the frontal view revealed an average smile line with a 90% incisal display, a non-consonant smile arc, and a wide buccal corridor. Notably, there was a 1 mm deviation of the maxillary dental midline to the right relative to the facial midline, with the lower midline coinciding relative to the facial midline.\n\nDuring intraoral examination, no carious lesions were found. However, mild plaque-induced gingivitis was present around all anterior permanent teeth. The patient exhibited an Angle’s Class I relationship.10 Canine relationships were classified as Class II. Specifically, the upper right permanent lateral incisor was lingually displaced and in a lingual crossbite. Retained lower right primary canine was the result of the odontoma that caused impaction of the lower right permanent canine. Additionally, there was bulging of the alveolar vestibule below the lower right primary canine. The overjet measured 2 mm, and the overbite was 17%. White, yellow, and brown stains were visible on the buccal and occlusal surfaces of the upper and lower permanent first molars. Facial surfaces of the upper right canine, upper central incisors, lower central incisor, and lower right lateral incisor exhibited white or creamy stains. Furthermore, the tooth size-arch length discrepancy was -4 mm in the maxillary arch and -2 mm in the mandibular arch, indicating mild upper and lower crowding (Figure 1).11\n\nPanoramic radiograph was acquired, which showed a radiopaque mass, consisting of multiple small, calcified tooth-like structures, surrounded an oval radiolucent lesion around the crown of the unerupted lower right permanent canine. No root resorption was observed, and no other anomalies or pathologies were noted. Cone-beam computed tomography was performed which confirmed the radiological diagnosis of compound odontoma with impaction of the lower right permanent canine.\n\nLateral cephalometric radiography indicated cervical vertebral maturation stage V, suggesting that the peak of mandibular growth occurred no earlier than 2 years before this stage.12 The anteroposterior position of the maxillary and mandibular jawbones showed an SNA of 81°, an SNB of 77°, and an ANB of 4°, indicating skeletal class II due to the retrognathic mandible. The Frankfort-mandibular plane angle (FMA) measured 24°, with a normodivergent mandibular plane angle.\n\nRegarding the upper anterior relation to the anterior cranial base, the SN-U1 angle was 104° (within the normal range), and the mandibular plane angle (IMPA) and Frankfort-mandibular incisor angle (FMIA) were 97° and 58°, respectively, indicating lingual inclination of the mandibular anterior teeth. The upper and lower lip positions relative to Ricketts’ esthetic line (E-line) were -2 mm and 2 mm, respectively, indicating a normal lip position.13,14 Figure 2A-F displays the radiographs, and Table 1 summarizes the cephalometric analysis.\n\nThe clinical appearance, combined with the radiographic findings, showed a diagnosis of compound odontoma associated with impacted mandibular right permanent canine. Transillumination assessment of the stains was performed by positioning the tip of a light-emitting diode (LED) light-curing unit at the palatal/lingual surfaces of teeth. Dark and intense color was observed which indicated towards deep stains (Figure 3). Considering both clinical and medical history, MIH was also diagnosed. According to the MIH-Treatment Need Index (MIH-TNI) criteria, the case was classified as MIH without hypersensitivity and without defect extension (MIH TNI 1).5\n\nDark and intense color indicates deep stains.\n\n\n3. Surgical intervention\n\nThe patient underwent surgical extraction of the lower right primary canine and excision of the odontoma. The surgical incision extended from the lower right second premolar to the lower right permanent central incisor. A distal releasing incision was made near the lower right second premolar, followed by subperiosteal dissection on the lingual side where the bulge was located. The odontoma was then removed intact. A subperiosteal flap exposed the lower right permanent canine, and buttons were placed on its lingual surface for traction. The biopsy sample was sent to the Oral Pathology Department, confirming a diagnosis of compound odontoma.\n\n\n4. Orthodontic intervention\n\nThe bonding of all upper and lower permanent teeth (except the lower right permanent canine) was carried out using a pre-adjusted edgewise appliance (0.018” × 0.025”) with the MBT prescription system (3M Unitek, Monrovia, California, USA) and 3MTM Transbond XT Light Cure Adhesive (3M company, St. Paul, Minnesota, USA). Additionally, the bracket of the upper right permanent lateral incisor was reversed to torque the root forward. Orthodontic bands were applied instead of molar tubes on all permanent first molars to enhance retention due to compromised enamel mineralization. Notably, the bracket bonding strength was suitable for both the upper and lower anterior teeth, and the patient did not encounter any instances of bracket bonding failure.\n\nInitially, the upper and lower dentitions were leveled and aligned using 0.014-inch and 0.016-inch nickel-titanium (NiTi) archwires. Subsequently, 0.016-inch stainless steel (SS) archwires were prescribed. After 6 months of treatment, a follow-up panoramic radiograph was taken to assess root parallelism. Some brackets were repositioned, and the archwires were downgraded to 0.016-inch NiTi. Later, the wires were progressed to 0.016-inch by 0.022-inch SS. An open-coil spring was then used to create space for the upper right permanent incisors and shift the upper midline toward the left side. Additionally, another open-coil spring was placed to create space for the lower right permanent canine. Traction was applied to the lower right permanent canine using an elastic chain with an average force of 60 grams. After 3 months, the lower right permanent canine began to erupt. Lingual root torque was applied to this tooth during the finishing stage. Finally, a 0.017-inch by 0.025-inch SS wire, along with class II elastics (60 grams), was used to achieve a class I canine relationship. Retention included a lower fixed retainer with an overlay Hawley retainer, while the upper arch was retained using an upper Hawley retainer. The total treatment duration was 25 months.\n\nPost-orthodontic follow-up was conducted at the time-point of 26 months. Upon examining the frontal view of the face, the maxillary dental midline aligned precisely with the lip philtrum and facial midline. The smile, as seen from the frontal view, displayed a harmonious smile arc with full visibility of the upper incisors. Intraoral examination revealed an Angle’s class I relationship, with appropriate overjet and overbite for the canines (Figure 4). Panoramic radiography confirmed proper root parallelism without any periodontal abnormalities. Additionally, both upper and lower third molars were in the developmental stage.\n\nThe cephalometric evaluation showed no significant change in both the SNA and SNB angles. The FMA angle increased slightly by 1°, indicating a minor clockwise rotation of the mandible. Dental analysis showed that the SN-U1 angle remained unchanged, but U1-NA decreased by 2°, suggesting forward displacement of the Nasion landmark. For the mandibular anterior teeth, the L1-NB angle increased by 4°, IMPA increased by 4°, and FMIA decreased by 1°, indicating labial tipping of the lower central incisors. The inter-incisal angle decreased by 4°, reflecting proclination of both upper and lower anterior teeth.\n\nSoft tissue analysis revealed slight retrusion of the upper and lower lips relative to the E line (Figure 5A, Figure 5B and Table 1). A cephalometric superimposition was performed using the Dolphin imaging software (Dolphin version 11.59, Dolphin Imaging and Management Solutions, Chatsworth, CA, USA) available at (https://www.dolphinimaging.com), which showed slight extrusion of the permanent first molars and proclination of upper and lower incisors (Figure 6A and Figure 6B). Following completion of orthodontic treatment, the patient was referred to a restorative dentist to enhance the aesthetics of the hypomineralized anterior teeth.\n\n(A) Overall superimposition: the black tracing indicates pretreatment (15 years, 7 months) and the red tracing indicates posttreatment (17 years, 8 months). (B) Maxillary and mandibular regional superimposition; the black tracing indicates pretreatment (15 years, 7 months) and the red tracing indicates posttreatment (17 years, 8 months).\n\n\n5. Restorative interventions\n\nPreventive strategies included educating both parents and patient about dental hygiene and caries prevention procedures at home, such as the use of fluoridated toothpaste. In-office measures included application of Fisseal Light Curing Pit and Fissure Sealant with Fluorides (PROMEDICA Dental Material GmbH, Germany) and professional fluoride in the form of gel to minimize dental caries and sensitivity. In addition, NovaMin® (GlaxoSmithKline Consumer Healthcare, Weybridge, Surrey, UK) dentifrice was prescribed to enhance dental remineralization and desensitization.5\n\n5.2.1 Bleaching\n\nIn light of the patient’s age, a minimally invasive approach was suggested to enhance the aesthetic condition of the teeth rather than traditional restorative treatment. Initially, dental prophylaxis using a non-drying, splatter-free Qartz prophy paste containing 1.23% fluoride and 0.1 molar phosphate (PearsonTM Dental, Sylmar, CA, USA) mixed with water (2:1 ratio) and supragingival scraping with periodontal curettes were used to stabilize the oral environment. In the subsequent session, the initial tooth shade was visually assessed using validated method the VITA classical A1-D4® shade guide. Required license has been obtained for the use of this tool (VitaZähnfabrik, Bad Säckingen, Germany).15 The upper incisors ranged from shades A3 to A3.5, while the canines were shade A3.5. The lower incisors were shade A3.5, and the canines were A4 (Figure 7A-C).\n\n(A) The upper incisors were presented in shade A3, and the canines in shade A3.5. (B) The lower teeth were presented in shade A3.5 for incisors, and (C) in shade A4 for canines.\n\nA digital impression was obtained using 3Shape CAD/CAM TRIOS® 4 and bleaching trays were created using Rubber Transparent (3A Medes Easy Vac Gaskets, India). Before using the trays, their proper adaptation to the teeth and gingival tissues was assessed. At the beginning of the bleaching session, a gingival barrier (OpalDam®, Ultradent Products, Inc., South Jordan, Utah, USA) was applied and light-cured for 20 seconds on the gingival contour of all teeth to protect against mucosal irritation. For the home bleaching technique, Opalescence® Boost 40% (Ultradent Products, Inc., South Jordan, Utah, USA) was used, a hydrogen peroxide-based agent prepared according to the manufacturer’s instructions. Two 20-minute applications of the bleaching agent were performed. After each session, the teeth were thoroughly rinsed with water. Subsequently, neutral colorless NovaBright™ 5% sodium fluoride varnish (Nanova Biomaterials, Inc., Columbia, Missouri, USA) was applied and allowed to dry for 10 minutes (Figure 8A-B).\n\nTo achieve more satisfactory aesthetic results, a second home bleaching treatment was performed using carbamide peroxide gel Opalescence™ PF 35% (Ultradent Products, Inc., South Jordan, UTAH, USA). The treatment involved daily application for 30 to 60 minutes over two weeks, followed by the use of sodium fluoride varnish. In the first week, the bleaching material was applied daily, and in the second week, it was used every day. At the end of each week the patient’s teeth and gingival tissues were evaluated. The patient received tooth whitening instructions, including tips to avoid coffee, soft drinks, and citrus fruit juices.\n\nAfter both bleaching procedures were finished, a 2-week waiting period was observed before the final shade evaluation during the patient’s recall visit. The patient’s teeth appeared brighter, with noticeable improvement in previously discolored areas. Figure 9 illustrates the results of home bleaching, showing the upper incisors, upper canines, lower incisors, and lower canines in shade A2.\n\n5.2.2 Resin infiltration\n\nTo improve the translucency and esthetics of teeth, resin infiltration was planned as next step after bleaching. The Icon® Vestibular (DMG, Hamburg, Germany) was performed according to the manufacturer’s instructions. The affected teeth were isolated using a rubber dam (Sanctuary® Powder-free Latex Silk Blue Dental Dam, Malaysia) and a clamp (HuFriedyGroup, STERIS, USA). A 15% hydrochloric acid was applied to the lesion using the 0.45 ml (Icon Etch, DMG, Hamburg, Germany). After allowing it to sit for 2 minutes, the tooth was rinsed with water for 30 seconds and dried using an air spray. After the third etching round, a 0.45 ml ethanol (Icon Dry, DMG, Hamburg, Germany) was applied to remove the water retained in the microporosities of the enamel, letting it last for 30 seconds. Subsequently, infiltrating resin was applied to the lesion using the 0.45 ml (Icon-Infiltrant, DMG, Hamburg, Germany). The resin infiltrant was massaged onto the lesion surface in circular movements for 3 minutes, ensuring thorough penetration. The excess resin was removed with air-spray and dental floss. Finally, the resin infiltrant was polymerized for 40 seconds using a light-cure device (Planmeca Lumion™ Plus polymerization light, Planmeca OY, Finland). The treatment protocol involved three rounds of hydrochloric acid application (2 minutes each) followed by a 10-minute infiltration period. An additional minute of treatment was administered after the initial infiltrating procedure. Upon completion, the rubber dam and clamps were removed, and surface finishing was performed using fine-grained polishing burs and the dental composite polishing diamond system RA Disc 14mm Wheel (Rubber Wheel, AZDENT, China) (Figure 10A-H).\n\n5.2.3 Restoration of posterior teeth\n\nAn indirect onlay restoration was performed on the upper right first molar due to cusp involvement. During the onlay preparation, efforts were made to completely remove the hypomineralized enamel and place the final preparation margins on sound, unaffected enamel. Approximately 1.5 mm reduction was done for the functional cusps (distolingual), and 1 mm reduction for the nonfunctional cusps (distobuccal). A butt joint margin was prepared using a long round end taper (856L) bur. A digital impression was obtained using the 3Shape CAD/CAM TRIOS 4 system. The temporary restoration was fabricated using the Ivoclar Vivadent Systemp. In the laboratory procedure, two sets of casts were printed using JamgHe 10K Standard Plus Resin for an LCD DLP SLA 405nm 3D Printer (High Transparent, 1000 g). The ceramic onlay was created using Ivoclar Vivadent AGFL-9494 Schaan/Liechtenstein in shade A2.\n\nDuring the try-in visit, the onlay was placed, followed by a bitewing radiograph. Subsequently, the onlay was etched with 9.5% hydrofluoric acid for 20 seconds, and a silane coupling agent (Deutschland GmbH Germany 3M ESPE) was applied for 1 minute. The temporary restoration was removed, and the molar was cleaned and etched using 37% phosphoric acid (ScotchbondTM Multi-Purpose Etchant, 3M ESPE) for 15 seconds, followed by rinsing with water for 15 seconds and drying with high-volume suction. The bonding agent (AdperTM Single Bond Plus, 3M ESPE) was actively applied, and dual-cure resin cement (RelyXTM Unicem 2 Clicker™100, 3M ESPE) was used for final cementation. After cementation, occlusion was assessed, and the onlay was finished and polished.\n\n\n6. Patient follow-up\n\nThe patient was followed up three months later after orthodontic debonding and restorative treatment (Figure 11). Oral hygiene was reinforced, and retainers were checked. Additionally, the patient exhibited no temporomandibular joint symptoms, and gingiva remained healthy. The patient was satisfied with the treatment outcomes and experienced improvements in esthetics and mastication. Her self-esteem increased significantly. Moreover, she was informed about the potential need for future extraction of all third molars.\n\n\n7. Discussion\n\nThe present case report describes a comprehensive management strategy for a patient with compound odontoma associated with impacted canine and MIH. The management involved the removal of odontoma to allow for orthodontic traction of the lower permanent right canine. Thereafter, esthetic appearance of the teeth was improved through restorative treatment.\n\nWhen considering the presence of odontomas associated with impacted teeth, it is important to highlight that the decision to remove it and extrude the impacted tooth varies based on patient-specificity. The failure rate for traction of the mandibular canines has been documented to be 17%.16 However, successful traction was possible in the present case. At the same instance, it is important to highlight that alternative treatment options should be opted where traction of the mandibular canine could be challenging owing to the deep location of impaction, possibility of ankylosis and presence of critical sized defect following odontoma removal. If ankylosis existed with deep impaction an alternative treatment option would be to extract the lower right permanent canine, excise the odontoma, mesialize the lower right posterior segment, and substitute the lower right first premolar for the lower right permanent canine. In addition, bone grafting should be opted for cases with large defects following odontoma removal, where traction of canine is planned. In the present case no grafting was performed owing to the small dimensions of the odontoma. However, future radiological studies are recommended to assess the impact of grafting and size of defect on the orthodontic traction of impacted teeth following odontoma removal.\n\nIn relation to MIH, it is a clinically challenging condition due to the compromised bonding of fixed orthodontic appliances. A failure of bracket system adherence to the defective enamel structure occurs, and the bracket may not be able to withstand active orthodontic forces. However, the presented patient did not experience bracket bonding failure or compromised orthodontic movement, as the hypocalcification was present on the incisal edge of the anterior teeth away from the bracket position. In cases with extended hypocalcification inhibiting the application of brackets, it has been proposed to either apply glass ionomer cement-based adhesives or perform microabrasion on hypomineralized enamel before etching.17 In addition, a study suggested that enamel deproteinization with 5% sodium hypochlorite prior to the bonding procedure might improve the bonding performance of resin adhesives to the hypomineralized enamel.18\n\nDebonding is another challenging factor in cases of MIH. Removal of the fixed orthodontic appliance could create stress on the defective enamel structure and lead to loss of the affected enamel with microfractures.8 In this case, a low-speed white stone bur was used to reduce damage to the enamel structure. A recent study also suggested the use of a laser or thermal method to reduce enamel fractures.19 In addition, hypersensitivity among patients with MIH has been reported owing to increased porosity and high protein concentrations.20 One potential cause of hypersensitivity in MIH is the inflammatory response in the pulp due to oral bacteria penetrating through the hypomineralized enamel into the dentinal tubules. Additionally, tooth hypersensitivity related to MIH also seems to be present in disintegrated molars immediately after tooth eruption. The management of such a condition involves preventive and therapeutic approaches, such as using fluoride varnishes and casein-based products. However, the presented case did not report any sensitivity.\n\nThe presented patient experienced unpleasant white spot lesions on the anterior teeth, prompting bleaching and resin infiltration. As a result, smile aesthetics improved, and the patient expressed satisfaction with the final outcome. A recent systematic review also advocated for using resin infiltration to conceal enamel fluorosis, while another study highlighted the effectiveness of bleaching as a treatment approach.\n\nThe primary strength of the case report lies in its first-time documentation of the comprehensive management of a patient with compound odontoma associated with an impacted tooth and MIH. However, it is important to interpret the findings with caution, as a single case cannot establish a cause-and-effect relationship. To confirm treatment outcomes and establish patient-specific treatment guidelines, further prospective studies with larger sample sizes and long-term follow-up are recommended.\n\n\n8. Conclusions\n\nThe case report highlights the successful management of a patient with compound odontoma, an impacted mandibular canine, and MIH. The treatment approach involved surgically removing the odontoma, followed by orthodontic intervention to guide the impacted canine into its proper position. Due to the presence of MIH, the orthodontic intervention was altered to include orthodontic bands instead of molar tubes, for improved retention and a conservative debonding procedure was performed with a low-speed handpiece. Additionally, cosmetic dental treatment was performed using bleaching and resin infiltration for the anterior teeth, and onlay restoration for maxillary right first molar.\n\n\nAuthor contributions\n\nConceptualization, N.A. and K.A.; Data curation, K. A. and M.A.A.; formal analysis, K.A., M.A., M.A.A., F.O.A., and S.S.; funding acquisition, N. A.; investigation, N.A., K.A., M.A., M.A.A., and F.O.A.; methodology, N.A.; project administration, N. A.; resources, N.A.; software, K.A.; supervision, N. A., M.A., and S.S.; validation, N.A.; visualization, N. A. and M.A.; writing—original draft preparation, N. A.; writing—review and editing, N. A., K. A., M.A., M.A.A., F.O.A., and S.S.\n\n\nConsent statement\n\nA written informed consent was obtained from the patient and parents to publish the current case report and accompanying images.",
"appendix": "Data availability\n\nNo data associated with this article.\n\n\nAcknowledgements\n\nNot applicable.\n\n\nReferences\n\nHidalgo-Sánchez O, Leco-Berrocal MI, Martínez-González JM: Metaanalysis of the epidemiology and clinical manifestations of odontomas. Med. Oral Patol. Oral Cir. Bucal. 2008; 13(11): 730–734.\n\nTekkesin MS, Pehlivan S, Olgac V, et al.: Clinical and histopathological investigation of odontomas: review of the literature and presentation of 160 cases. J. Oral Maxillofac. Surg. 2012; 70(6): 1358–1361.\n\nSarica İ, Derindağ G, Kurtuldu E, et al.: A retrospective study: Do all impacted teeth cause pathology? Niger. J. Clin. Pract. 2019; 22(4): 527–533. PubMed Abstract | Publisher Full Text\n\nDunfee BL, Sakai O, Pistey R, et al.: Radiologic and pathologic characteristics of benign and malignant lesions of the mandible. Radiographics. 2006; 26(6): 1751–1768. PubMed Abstract\n\nLygidakis N, Garot E, Somani C, et al.: Best clinical practice guidance for clinicians dealing with children presenting with molar-incisor-hypomineralisation (MIH): an updated European Academy of Paediatric Dentistry policy document. Eur. Arch. Paediatr. Dent. 2022; 23(1): 3–21. PubMed Abstract | Publisher Full Text\n\nSilva MJ, Scurrah KJ, Craig JM, et al.: Etiology of molar incisor hypomineralization–A systematic review. Community Dent. Oral Epidemiol. 2016; 44(4): 342–353. PubMed Abstract | Publisher Full Text\n\nElhennawy K, Schwendicke F: Managing molar-incisor hypomineralization: A systematic review. J. Dent. 2016; 55: 16–24. PubMed Abstract | Publisher Full Text\n\nKoletsi D, Gerald Bradley T, Kavvadia K: Bonding and Debonding Considerations in Orthodontic Patients Presenting Enamel Structural Defects. Debonding and Fixed Retention in Orthodontics: An Evidence-Based Clinical Guide. 2023; pp. 43–62.\n\nRiley DS, Barber MS, Kienle GS, et al.: CARE guidelines for case reports: explanation and elaboration document. J. Clin. Epidemiol. 2017; 89: 218–235. PubMed Abstract | Publisher Full Text\n\nKatz MI: Angle classification revisited 2: a modified Angle classification. Am. J. Orthod. Dentofacial Orthop. 1992; 102(3): 277–284. PubMed Abstract\n\nKirschen RH, O’Higgins EA, Lee RT: The Royal London Space Planning: an integration of space analysis and treatment planning: Part I: Assessing the space required to meet treatment objectives. Am. J. Orthod. Dentofacial Orthop. 2000; 118(4): 448–455. PubMed Abstract\n\nBaccetti T, Franchi L, McNamara JA Jr: An improved version of the cervical vertebral maturation (CVM) method for the assessment of mandibular growth. Angle Orthod. 2002; 72(4): 316–323. PubMed Abstract\n\nNg JHH, Singh P, Wang Z, et al.: The reliability of analytical reference lines for determining esthetically pleasing lip position: An assessment of consistency, sensitivity, and specificity. Am. J. Orthod. Dentofacial Orthop. 2023 Jul; 164(1).\n\nRicketts RM: Planning treatment on the basis of the facial pattern and an estimate of its growth. Angle Orthod. 1957; 27(1): 14–37.\n\nMeireles SS, Demarco FF, Santos IS, et al.: Validation and reliability of Visual Assessment with a shade guide for tooth-color classification. Oper. Dent. 2008 Mar 1; 33(2): 121–126. PubMed Abstract | Publisher Full Text\n\nDalessandri D, Parrini S, Rubiano R, et al.: Impacted and transmigrant mandibular canines incidence, aetiology, and treatment: a systematic review. Eur. J. Orthod. 2017; 39(2): 161–169. PubMed Abstract | Publisher Full Text\n\nMarure PS, Mahamuni A, Ambekar AS, et al.: Orthodontic bracket bonding challenge for fluorosed teeth. J. Int. Oral Health. 2016; 8(4): 476–480.\n\nEkambaram M, Yiu C: Bonding to hypomineralized enamel–A systematic review. Int. J. Adhes. Adhes. 2016; 69: 27–32.\n\nGibas-Stanek M, Pełka P, Pihut M: What is the safest method of orthodontic debonding - a systematic review of the literature. Folia Med. Cracov. 2023; 63(3): 133–156. PubMed Abstract | Publisher Full Text\n\nLyaruu D, Bervoets T, Bronckers A: Short exposure to high levels of fluoride induces stage-dependent structural changes in ameloblasts and enamel mineralization. Eur. J. Oral Sci. 2006; 114 Suppl 1: 111–115. PubMed Abstract"
}
|
[
{
"id": "328480",
"date": "30 Dec 2024",
"name": "Jie Jia",
"expertise": [
"Reviewer Expertise dentist"
],
"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 writing of this manuscript is acceptable. The exact clinical diagnosis of this patient was correct, and the surgical intervention and orthodontic treatment, as well as restoration of anterior teeth were satisfactory.\nThis report presents a comprehensive treatment of odontoma and molar-incisor hypomineralisation in orthodontics. In general, the exact clinical diagnosis of this patient was correct, and the surgical intervention and orthodontic treatment, as well as restoration of anterior teeth were satisfactory. The total treatment obtained a relatively satisfied effects of this case. I have the following comments for further improvement:\n1. The language of this manuscript need improved. 2. In the second paragraph of introduction \"Moreover, MIH is a prevalent dental developmental disorder that affects approximately 10% to 20% of children and adolescents\", the prevalence of MIH is 2.4%- 40.2% in global, please find the correct reference. 3. In the Clinical examination part, most index teeth have the defect of MIH. We know that hypersensitivity is the most symptom of MIH. Considering that this patient need to received orthodontic treatment, bleaching, resin infiltration, but the author did not illustrate how to avoid the hypersensitivity during the treatment. 4. For the restoration of posterior teeth, why perform an indirect onlay restoration for the posterior teeth other than regular resin restoration, and whether show the intraoral effect of the onlay restoration?\n\nReport presents the successful orthodontic management of a case of odontoma associated with impaction of the mandibular right permanent canine and Molar-incisor-hypomineralization (MIH)\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
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https://f1000research.com/articles/13-970
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https://f1000research.com/articles/13-617/v1
|
11 Jun 24
|
{
"type": "Research Article",
"title": "Zoom fatigue related to online learning among medical students in Thailand: Prevalence, predictors, and association with depression",
"authors": [
"Veevarin Charoenporn",
"Sirashat Hanvivattanakul",
"Kanathip Jongmekwamsuk",
"Rinradee Lenavat",
"Korravit Hanvivattanakul",
"Thammanard Charernboon",
"Veevarin Charoenporn",
"Sirashat Hanvivattanakul",
"Kanathip Jongmekwamsuk",
"Rinradee Lenavat",
"Korravit Hanvivattanakul"
],
"abstract": "Background Amidst the COVID-19 pandemic, the learning pattern of medical students shifted from onsite to online. This transition may contribute to what has been called “Zoom fatigue.” This study aimed to evaluate the prevalence of Zoom fatigue related to online learning, identify associated factors of Zoom fatigue, and explore its correlation with depression among medical students during the COVID-19 pandemic.\n\nMethods This cross-sectional study was conducted among 1st to 6th-year Thai medical students. The online survey was administered using a demographic and health behavior questionnaire, the Patient Health Questionnaire-9 (PHQ-9), and the Thai version of the Zoom Exhaustion & Fatigue Scale (ZEF-T).\n\nResults Among the 386 participating students, 221 (57%) were female, with a mean age of 20.6 years. The prevalence of high Zoom fatigue was 9.6%. In the multivariable regression analysis, a lower academic year and a higher number of online learning sessions were significant predictors of Zoom fatigue (p < 0.001), while regular exercise emerged as a protective factor (p = 0.009). The prevalence of depressive disorder was 61.9%, and a significant correlation was found between having a depressive disorder and experiencing Zoom fatigue (p = 0.004).\n\nConclusion Zoom fatigue among medical students was correlated with depression. Consequently, medical students experiencing Zoom fatigue should undergo further assessment for depression. It is crucial to closely monitor medical students in lower academic years with a high number of online sessions for signs of Zoom fatigue. Additionally, implementing strategies, such as reducing the frequency of online sessions and promoting regular exercise, may help alleviate the symptoms.",
"keywords": [
"depression",
"medical students",
"online learning",
"videoconferencing fatigue",
"Zoom fatigue"
],
"content": "Introduction\n\nSince the start of 2020, COVID-19, caused by the SARS-CoV-2 virus, has quickly spread worldwide, becoming a major global health crisis. This pandemic has led to unpredictable and mandatory transformations on a global scale, profoundly impacting the lives of individuals worldwide.1 The WHO has recommended implementing several preventive strategies, such as social distancing measures, restrictive regulations, self-quarantine, and transitioning to remote work, to reduce the spread of the COVID-19 pandemic and minimize mortality rates.2 In the realm of education, these changes have contributed to the new normal lifestyle where face-to-face and onsite learning have become impractical. Online lectures have become the standard, common, and fostering the widespread use of online meeting applications like Google Classroom, Google Meet, Zoom, Webex, and Microsoft Teams as major platforms for online learning.3\n\nZoom emerged as one of the most popular videoconferencing platform for online learning during the COVID-19 pandemic. It is used for both personal and business purposes. The number of daily users skyrocketed from 10 million in December 2019 to 300 million in April 2020, making it the fastest-growing application in 2020.4 However, excessive use of videoconferencing can lead to the novel phenomenon called “Zoom fatigue” or “Zoom exhaustion,” defined as physical and mental exhaustion from participating in virtual meetings through any online meeting application.5 This condition may manifest in several domains, including general, emotional, visual, motivational, and social fatigue.6\n\nThe study postulated the phenomenon of Zoom fatigue, linked to the excessive use of nonverbal communication in video conferencing. In comparison to regular meetings, video conferencing requires heightened concentration and attention. Various factors contribute to Zoom fatigue, including eye strain from prolonged close-range staring, increased cognitive load processing information in video calls, self-consciousness from constant self-reflection during calls, and restricted body movements in online sessions. Additionally, external factors beyond one’s control, such as internet disruptions, the pressure to respond to speaker questions, and environmental conditions, can exacerbate Zoom fatigue. Therefore, the condition of Zoom fatigue may impact individuals’ overall well-being.7\n\nA specific assessment tool to measure video-related fatigue, called the Zoom Exhaustion and Fatigue (ZEF) scale, was developed at Stanford University in 2021.6 It comprises 15 items and assesses five domains: general fatigue, visual fatigue, social fatigue, motivation fatigue, and emotional fatigue. The scale has been translated into several languages.8,9\n\nMedical students have faced profound challenges due to the COVID-19 pandemic and the transition to online learning. In a cross-sectional study conducted at a Brazilian medical school using the ZEF scale, findings revealed that up to 56% of participants experienced high levels of Zoom fatigue.10 Beyond Zoom fatigue, studies also indicate a substantial increase in depression, anxiety, and mental problems, especially among university students, during the COVID-19 pandemic.11–14 These findings suggest that university students, particularly medical students, are among the populations most affected by the mental health consequences of the pandemic, facing a heightened risk of developing depression and psychological problems.14\n\nIn addition, several studies have demonstrated the relationship between Zoom fatigue and mental health conditions. A national survey conducted in the United States during the pandemic found a link between Zoom fatigue and depressive symptoms.15 Another study also showed a positive correlation between Zoom fatigue and depression, anxiety, and stress, while showing a negative correlation between Zoom fatigue and life satisfaction and academic well-being.16\n\nHowever, to the best of our knowledge, to date, there are still few studies examining the prevalence of Zoom fatigue and its potential association with depression, with no such study conducted among medical students in Thailand. Therefore, our study aims to assess the prevalence of Zoom fatigue in medical students during the COVID-19 pandemic, identify associated potential risk factors, and investigate its correlation with depression.\n\n\nMethods\n\nA cross-sectional online survey was conducted among medical students during the academic year 2565 at Thammasat University, Thailand, from January to July 2022. This study received approval from the Human Research Ethics Committee of the Faculty of Medicine, Thammasat University (number 028/2565; date of approval: January 26, 2022), in accordance with the Declaration of Helsinki. Signed informed consent was waived by the Ethics Committee due to the online nature of the survey; however, participants were provided with study information on the first page.\n\nThe recruitment process involved 386 medical students from Thammasat University. To meet the inclusion criteria, participants had to be Thammasat medical students aged at least 18 and proficient in Thai. They were requested to complete an anonymous online survey questionnaire using Google Forms, which was distributed through various online platforms such as LINE, university forums, and an exclusive Facebook group for Thammasat medical students. The survey tool automatically verified that all questions were completed before submission; therefore, our study had no missing data. No compensation or incentives were offered to participants. Confidentiality and privacy of data were ensured throughout the study process.\n\nThe questionnaire comprised demographic data, the Thai version of the Patient Health Questionnaire (PHQ)-9, and the Thai version of the Zoom Exhaustion and Fatigue Scale (ZEF-T).\n\nDemographic Data\n\nThe basic general information includes gender, age, academic year, underlying disease, the number of online sessions per day, duration of each online session, time taken for each break during online sessions, exercise frequency, sleep problems, and experience of failing an examination.\n\nThe Zoom Exhaustion & Fatigue Scale (ZEF)\n\nThe ZEF is a questionnaire comprising 15 items that assess the symptoms experienced by participants during video conferences. The questions are categorized into five domains, including general fatigue, visual fatigue, social fatigue, motivation fatigue, and emotional fatigue. Each question on the questionnaire is scored from 1 to 5 (1 = not at all, 2 = slightly, 3 = moderately, 4 = very, 5 = extremely), resulting in a total score ranging from 15 to 75 points. A higher score indicates a higher level of Zoom fatigue.6,8 The average total ZEF score is calculated by dividing the total ZEF score by 15. We established a cutoff score for Zoom fatigue as an average total ZEF score of ≥4 to identify individuals experiencing Zoom fatigue. The ZEF was granted permission to be used and translated by Fauville G.\n\nThe Patient Health Questionnaire (PHQ-9)\n\nThe Patient Health Questionnaire (PHQ-9) is a self-assessment tool comprising nine questions designed to evaluate the frequency of symptoms associated with depression over a two-week period. The questionnaire employs a rating scale ranging from 0 to 3 points, with categories including none (0 points), some days but not often (1 point), quite often (2 points), and almost every day (3 points). The total score obtained ranges from 0 to 27 points, with a higher score indicating more severe depressive symptoms.17 In this study, we applied a cutoff score of ≥9 points, based on the PHQ-9 Thai version, to identify individuals experiencing depression.18 PHQ-9 is publicly available, and no permission is required to use, reproduce, or distribute the tools. https://www.apa.org/depression-guideline/patient-health-questionnaire.pdf.\n\nThe sample size was determined using the infinite population proportion formula, with proportion = 0.48,10 error (d) = 0.05, alpha (α) = 0.05, and Z = 1.96. The calculated sample size was determined to be at least 384 students. Participant characteristics were presented using descriptive statistics. Multivariable linear regression analysis was employed to examine the factors associated with Zoom fatigue scores. Exact tests were utilized to analyze the association between depression and Zoom fatigue. All statistical calculations were performed using STATA Version 14.0 (StataCorp LLC, College Station, TX, USA), with statistical significance set at a p-value less than 0.05.\n\n\nResults\n\nMost participants were female (57.3%), with a mean age of 20.6 years. The majority were third-year medical students (29.3%), followed by first-year (26.4%). About 18.4% of participants reported having an underlying disease. The average number of Zoom sessions per day was 1.9, with 83.7% of participants having sessions lasting one hour or more. Regarding sleep, 56.0% of participants reported not getting enough sleep, and 62.2% reported exercising sometimes. (Table 1).\n\nTable 2 shows the mean total ZEF score and its subscales, including general fatigue, visual fatigue, social fatigue, motivation fatigue, and emotional fatigue. The average total mean score for the ZEF was 2.8 indicating a slight level of Zoom fatigue. The highest subscores were observed in the general fatigue and social fatigue domains at 9.2 points, while the emotional fatigue had the lowest score at 7.3.\n\nTable 3 presents the levels of Zoom fatigue. The majority of participants (54.1%) reported experiencing no or only a slight level of Zoom fatigue. The overall prevalence of Zoom fatigue among participants was found to be 9.6%, categorized as a very/extremely high level of Zoom fatigue, with an additional 36.3% experiencing a moderate level of Zoom fatigue.\n\nThe prevalence of depression among the participants was 61.9% (n = 239). The results reveal a statistically significant relationship between having depression and Zoom fatigue (p = 0.004). Participants experiencing Zoom fatigue had a higher prevalence of depression compared to those without Zoom fatigue (83.8% vs 59.6%) (Table 4).\n\nTable 5 presents a multivariable linear regression analysis demonstrating factors associated with the ZEF total scores. The analysis found that education year, regular exercise, and the number of Zoom sessions per day were significantly associated with total ZEF scores. Specifically, a lower education year was associated with higher ZEF scores (coefficient = -2.44, p < 0.001), while regular exercise was associated with lower ZEF scores (coefficient = -5.27, p = 0.009). Conversely, a higher number of Zoom sessions per day was associated with higher ZEF scores (coefficient = 2.72, p < 0.001). Gender, age, underlying disease, not getting enough sleep, duration of breaks between sessions, and having failed an exam were not found to be statistically significant factors associated with ZEF scores.\n\n\nDiscussion\n\nTo the best of our knowledge, this study represents the first investigation in Thailand into the prevalence of Zoom fatigue, associated factors, and its correlation with depression among Thai medical students during the COVID-19 pandemic. The results of the study reveal a 9.6% prevalence of Zoom fatigue among Thai medical students as a consequence of online learning during the pandemic. Furthermore, the study uncovers a significant relationship between Zoom fatigue and depression, emphasizing the importance of addressing both conditions, as they may impact students’ well-being and overall quality of life.15\n\nOur study revealed that the occurrence of Zoom fatigue among medical students was significant and supports the idea that it is a common phenomenon among individuals using online platforms for learning. The high prevalence may be explained by the implementation of social distancing measures throughout the country, with the university mandating the use of online learning for all lectures and restricting onsite sessions. This led to the necessity of attending at least two online sessions per day, each averaging over an hour per session. These online sessions demanded prolonged concentration, extended close-range staring, and a high cognitive load in learning and using videoconference programs.5,6\n\nThe prevalence in our study aligns with previous research conducted during the COVID-19 pandemic, which demonstrated moderately to high Zoom fatigue ranging from 48% to 68.6%.10,19 Slight variations may be attributed to various factors such as videoconferencing time, study faculty, study type (hybrid or online only), and the type of online learning (lecture or more interactive meeting). Another crucial factor is that Zoom fatigue is a relatively new concept, lacking a worldwide standard criteria like major depressive disorder in DSM-5 or ICD-10. Therefore, the definition may vary between studies and depend on the questionnaires used. Consequently, it might be challenging at this time to directly compare the prevalence of Zoom fatigue between studies.\n\nThe study identified a significant correlation between Zoom fatigue and depression, with a substantial number of participants experiencing both Zoom fatigue and depression. Consistent with our findings, other studies, such as those by Elbogen et al. and Montag et al., also reported similar findings, indicating that depressive symptoms exhibited a significant association with Zoom fatigue, even when adjusting for demographic, psychosocial, and clinical covariates.15,20 The connection between these two conditions might be explained by the overlapping symptoms observed in both Zoom fatigue and depression. For instance, social fatigue translates into an unwillingness to engage with others after videoconferences, while motivation fatigue reflects a diminished drive following such sessions. These symptoms bear a striking resemblance to the loss of interest commonly seen in major depressive disorders. Moreover, irritability and moodiness can also be found in depressive disorders. The connection between Zoom fatigue and depression may also be elucidated by the social isolation and loneliness associated with both conditions. Higher videoconference use might indicate increased social isolation and loneliness, contributing to the development or exacerbation of depression. Additionally, several studies have indicated that Zoom fatigue is linked not only to depression but also to psychological distress and lower life satisfaction.16\n\nThis finding is unsurprising and aligns with the majority of previous studies that have demonstrated a correlation between an increased number of video conferencing sessions and higher fatigue.6,19,21 Our study also identified lower academic years as another notable risk factor. This observation may be attributed to the relatively greater number of lecture hours in the preclinical years (1st – 3rd year) compared to the clinical years (4th – 6th year). Clinical medical students dedicate a substantial amount of time to engaging with patients in hospitals and participating in hands-on learning activities, including basic skill workshops and bedside teaching. Their education primarily focuses on real patient cases encountered in a hospital setting, rather than relying on theory-based lectures. Even during the pandemic, clinical students continue to work in hospitals and participate in bedside teaching, resulting in lower video conferencing usage. On the other hand, preclinical students mainly learn through lectures. Therefore, the challenges brought about by the transition to online learning during the pandemic may have affected preclinical students more than clinical students. This is consistent with previous studies conducted on both medical and non-medical students, which revealed that students in the lower academic years were more susceptible to experiencing mental distress related to their studies.22\n\nRegular exercise has been identified as a protective factor against Zoom fatigue, suggesting that students consistently engaging in physical activity may exhibit better resilience to online learning challenges, reducing the likelihood of experiencing Zoom fatigue. This association can be explained by considering one of the underlying causes of Zoom fatigue—limited mobility or constrained body movements. Regular exercise promotes increased body movement, potentially mitigating the onset of Zoom fatigue.7 Furthermore, compelling evidence indicates that exercise prevents various mental disorders, such as depression and anxiety disorders, offering multiple beneficial effects on both physical and mental health. Therefore, exercise may also play a role in preventing Zoom fatigue.23\n\nThis study represents the initial exploration of the adverse effects of online learning on medical students in Thailand, revealing a potential connection between Zoom fatigue and depression. However, certain limitations must be acknowledged. The cross-sectional nature of the study prevents the establishment of a causal relationship. Additionally, the reported prevalence might be underestimated due to voluntary sample collection, potentially excluding highly fatigued students from survey participation. The novelty of the concept of Zoom fatigue has resulted in relatively limited research on this topic. Moreover, the lack of standardized criteria in various studies hampers direct prevalence comparisons. Lastly, the study did not clearly differentiate between the use of online meeting programs for lectures or interactive meetings. Further investigations are recommended to distinguish Zoom fatigue arising from online lectures and meetings distinctly.\n\n\nConclusion\n\nTo date, the use of video conferencing in education persists beyond the pandemic, becoming a part of our new normal lifestyle. It is imperative for instructors and users to recognize Zoom fatigue as a potential negative consequence. The significant prevalence of Zoom fatigue among medical students, along with its correlation with depression, emphasizes the importance of screening for both conditions, especially in lower academic years. Implementing proactive strategies, such as reducing session lengths and frequency, and promoting regular exercise, may contribute to symptom prevention.\n\nThis study received approval from the Human Research Ethics Committee of the Faculty of Medicine, Thammasat University (number 028/2565; date of approval: January 26, 2022), in accordance with the Declaration of Helsinki. Signed informed consent was waived by the Ethics Committee due to the online nature of the survey; however, participants were provided with study information on the first page.",
"appendix": "Data availability\n\nThe data supporting the findings of this study are available on Figshare: “Zoom fatigue among medical students” at https://doi.org/10.6084/m9.figshare.25407883. This project contains the raw data of the study.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nA copy of the Thai version of the ZEF questionnaire used in the study is available on Figshare: “Zoom Exhaustion & Fatigue Scale - Thai Version (ZEF-T)” at https://doi.org/10.6084/m9.figshare.25407931. The original English version of the ZEF can be accessed from Fauville G, Luo M, Queiroz ACM, Bailenson JN, Hancock J. Zoom Exhaustion & Fatigue Scale. Comput Hum Behav Rep. 2021;4:100119. 6\n\nChecklist for the manuscript is available on Figshare: “STROBE checklist Zoom fatigue” at https://doi.org/10.6084/m9.figshare.25487410.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgement\n\nWe would like to express our gratitude to the staff in the Student Affairs Department of the Faculty of Medicine at Thammasat University for their valuable assistance in distributing the electronic invitation poster and online survey link. Additionally, we extend our thanks to all the students who participated in this study. During the proofreading of this manuscript, the authors utilized ChatGPT for proofreading and improving readability. All authors have reviewed and approved the final manuscript.\n\n\nReferences\n\nWu YC, Chen CS, Chan YJ: The outbreak of COVID-19: An overview. J. Chin. Med. Assoc. 2020; 83(3): 217–220. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNussbaumer-Streit B, Mayr V, Dobrescu AI, et al.: Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review. Cochrane Database Syst. Rev. 2020; 9(9): CD013574. PubMed Abstract | Publisher Full Text\n\nCamargo CP, Tempski PZ, Busnardo FF, et al.: Online learning and COVID-19: a meta-synthesis analysis. Clinics (Sao Paulo). 2020; 75: e2286. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChawla A: Coronavirus (COVID-19)–‘Zoom’application boon or bane. Available at SSRN 3606716. 2020.\n\nRiedl R: On the stress potential of videoconferencing: definition and root causes of Zoom fatigue. Electron. Mark. 2022; 32(1): 153–177. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFauville G, Luo M, Queiroz ACM, et al.: Zoom Exhaustion & Fatigue Scale. Comput. Hum. Behav. Rep. 2021; 4: 100119. Publisher Full Text\n\nBailenson JN: Nonverbal overload: A theoretical argument for the causes of Zoom fatigue. TMB. 2021; 2(1): 1–5. Publisher Full Text\n\nCharoenporn V, Charernboon T: Validity and reliability of the Thai version of the Zoom Exhaustion and Fatigue Scale (ZEF-T). Fatigue. 2023; 11(2-4): 105–112. Publisher Full Text\n\nSalim J, Arnindita JN, Tandy S: Validation of the Indonesian translated Zoom Exhaustion and Fatigue (ZEF-I) scale: a RASCH Model and Factor Analysis. Fatigue. 2022; 10(2): 107–118. Publisher Full Text\n\nde Oliveira Kubrusly Sobral JB , DLF L, Lima Rocha HA, et al.: Active methodologies association with online learning fatigue among medical students. BMC Med. Educ. 2022; 22(1): 74. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShah SMA, Mohammad D, Qureshi MFH, et al.: Prevalence, psychological responses and associated correlates of depression, anxiety and stress in a global population, during the Coronavirus disease (COVID-19) pandemic. Community Ment. Health J. 2021; 57(1): 101–110. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSafa F, Anjum A, Hossain S, et al.: Immediate psychological responses during the initial period of the COVID-19 pandemic among Bangladeshi medical students. Child Youth Serv. Rev. 2021; 122: 105912. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOzamiz-Etxebarria N, Dosil-Santamaria M, Picaza-Gorrochategui M, et al.: Stress, anxiety, and depression levels in the initial stage of the COVID-19 outbreak in a population sample in the northern Spain. Cad. Saude Publica. 2020; 36(4): e00054020. PubMed Abstract | Publisher Full Text\n\nPeng P, Hao Y, Liu Y, et al.: The prevalence and risk factors of mental problems in medical students during COVID-19 pandemic: A systematic review and meta-analysis. J. Affect. Disord. 2023; 321: 167–181. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElbogen EB, Lanier M, Griffin SC, et al.: A National study of zoom fatigue and mental health during the COVID-19 pandemic: Implications for future remote work. Cyberpsychol. Behav. Soc. Netw. 2022; 25(7): 409–415. PubMed Abstract | Publisher Full Text\n\nDeniz ME, Satici SA, Doenyas C, et al.: Zoom fatigue, psychological distress, life satisfaction, and academic well-being. Cyberpsychol. Behav. Soc. Netw. 2022; 25(5): 270–277. PubMed Abstract | Publisher Full Text\n\nKroenke K, Spitzer RL, Williams JB: The PHQ-9: validity of a brief depression severity measure. J. Gen. Intern. Med. 2001; 16(9): 606–613. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLotrakul M, Sumrithe S, Saipanish R: Reliability and validity of the Thai version of the PHQ-9. BMC Psychiatry. 2008; 8: 46. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLestari PW, Fayasari A: Zoom fatigue during the COVID-19 pandemic: Is it real? Kesmas. Jurnal Kesehatan Masyarakat Nasional (National Public Health Journal). 2022; 17(2): 151–156.\n\nMontag C, Rozgonjuk D, Riedl R, et al.: On the associations between videoconference fatigue, burnout and depression including personality associations. J. Affect. Disord. Rep. 2022; 10: 100409. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOducado RMF, Dequilla M, Villaruz JF: Factors predicting videoconferencing fatigue among higher education faculty. Educ. Inf. Technol (Dordr). 2022; 27(7): 9713–9724. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWathelet M, Duhem S, Vaiva G, et al.: Factors associated with mental health disorders among university students in France confined during the COVID-19 pandemic. JAMA Netw. Open. 2020; 3(10): e2025591. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchuch FB, Vancampfort D: Physical activity, exercise, and mental disorders: it is time to move on. Trends Psychiatry Psychother. 2021; 43(3): 177–184. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "291510",
"date": "26 Jun 2024",
"name": "Pichai Ittasakul",
"expertise": [
"Reviewer Expertise Mood disorders",
"Psychiatry"
],
"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 am writing to provide my opinion regarding the research paper I was invited to review for F1000Research. The paper explores the prevalence of Zoom fatigue related to online learning among medical students and identifies associated factors and correlations with depression in this population. I find the topic highly relevant and interesting, particularly in light of the increased use of Zoom for teaching during the COVID-19 pandemic in Thailand. This research contributes valuable insights into medical education and the mental health of medical students. Overall, the paper is well-written and presents its findings clearly. However, I recommend that the authors address the limitations regarding the generalizability of their findings, as the sample was collected from a single medical school in Thailand. Including this discussion would enhance the robustness of the study. Thank you for the opportunity to review this paper.\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": "12168",
"date": "27 Aug 2024",
"name": "Thammanard Charernboon",
"role": "Author Response",
"response": "Author Response: Thank you for the comment. We have added the limitation as follows: “This study represents the initial exploration of the adverse effects of online learning on medical students in Thailand, revealing a potential connection between Zoom fatigue and depression. However, certain limitations must be acknowledged. Participants were recruited from a single site, which may limit the generalizability of the findings, and the results might not be applicable to other faculties.”"
}
]
},
{
"id": "291515",
"date": "11 Jul 2024",
"name": "Jonathan Salim",
"expertise": [
"Reviewer Expertise Medical Research and Application",
"Epidemiology",
"NTDs"
],
"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 Zoom Fatigue article on the F1000 platform.\nThe article corroborates that excessive online learning using Zoom or similar apps can exacerbate or induce student fatigue. It may lead to mental issues such as depression.\nOnline learning and Zoom fatigue have become an essential topic to be discussed since the lockdown of the pandemic. However, some improvements are required to be addressed:\n1. The article needs more reasons why it should be done in the first place, or simply the research gap. Reproducing the ZEF questionnaire into many languages and producing a paper just because of differences in language would result in over a hundred papers on the same thing.\n2. Why the sample used in this study is medical students? Please address the sample selection and limited generalisability.\n3. Please elaborate on what you mean by \"academic year 2565\". Is the academic year in Thammasat different from the calendar year?\n4. Why are there no criteria for zoom usage in the participants' inclusion criteria? Adult students who just enrolled in the university and are proficient in Thai but do not do any Zoom online learning then can be included as study samples, which can lead to bias\n5. The study did account for missing data by making the questions required, yet did the authors filter for duplicates? since the survey was distributed through a lot of different medium. One student may fill in the survey from both the LINE group and Facebook group for example.\n6. It would be nice if the authors could provide how the ZEF questionnaire was translated into the Thai version. An invalid or unreliable translation method or procedure may generate invalid results.\n7. English language improvements are needed in some areas for an increase in readability and coherency.\nThank you.\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": "12169",
"date": "27 Aug 2024",
"name": "Thammanard Charernboon",
"role": "Author Response",
"response": "Reviewer 2 Thank you for your comments. We have responded to all of your concerns and hope our revisions address them comprehensively. Reviewer Comment: Online learning and Zoom fatigue have become an essential topic to be discussed since the lockdown of the pandemic. However, some improvements are required to be addressed: 1. The article needs more reasons why it should be done in the first place, or simply the research gap. Reproducing the ZEF questionnaire into many languages and producing a paper just because of differences in language would result in over a hundred papers on the same thing. Author Response: Thank you for your comments. We have responded to all of your concerns and hope our revisions address them comprehensively. I have added to and rewritten our introduction as follows: “Due to its relatively recent emergence, Zoom fatigue has been the subject of limited research. Studies specifically focusing on medical students are even scarcer. Medical students differ significantly from other student populations, undergoing a six-year curriculum that includes clinical practice and often demanding on-call shifts. Understanding the risk factors for Zoom fatigue in this population could inform tailored prevention strategies and potentially mitigate negative impacts on academic performance and clinical decision-making. During the COVID-19 pandemic, all lectures at our university were delivered online, exposing the entire medical student body to this learning modality. To our knowledge, there are still only a few studies examining the prevalence of Zoom fatigue, its risk factors, and its potential association with depression, with no such study conducted among medical students in Thailand. To fill this knowledge gap, our study aims to assess the prevalence of Zoom fatigue in medical students during the COVID-19 pandemic, identify associated potential risk factors, and investigate its correlation with depression.” Reviewer Comment: 2. Why the sample used in this study is medical students? Please address the sample selection and limited generalisability. Author Response: We focused on medical students because this program is demanding, spans six years, and includes clinical practice, which differentiates this sample from those in other faculties. We acknowledge this limitation in generalizability and have addressed it in the discussion as follows: “However, certain limitations must be acknowledged. Participants were recruited from a single site, which may limit the generalizability of the findings, and the results might not be applicable to other faculties.” Reviewer Comment: 3. Please elaborate on what you mean by \"academic year 2565\". Is the academic year in Thammasat different from the calendar year? Author Response: We have removed this sentence to reduce confusion. We now describe the study period as follows: “A cross-sectional online survey was conducted among medical students at Thammasat University, Thailand, from January to July 2022.” Reviewer Comment: 4. Why are there no criteria for zoom usage in the participants' inclusion criteria? Adult students who just enrolled in the university and are proficient in Thai but do not do any Zoom online learning then can be included as study samples, which can lead to bias Author Response: The study was conducted during the COVID-19 pandemic when the university mandated the use of videoconferencing for all lectures. Therefore, we believe that all participants were exposed to online learning. We have added this information to the Introduction section as follows: “During the COVID-19 pandemic, all lectures at our university were delivered online in compliance with government regulations, exposing the entire medical student body to this learning modality.” Reviewer Comment: 5. The study did account for missing data by making the questions required, yet did the authors filter for duplicates? since the survey was distributed through a lot of different medium. One student may fill in the survey from both the LINE group and Facebook group for example. Author Response: We did not check for the duplication of participants. Due to the confidentiality of the survey, we did not record names, surnames, or other identifying information of the participants. However, since there is no incentive for the survey, we expect that duplication should be very low. Reviewer Comment: 6. It would be nice if the authors could provide how the ZEF questionnaire was translated into the Thai version. An invalid or unreliable translation method or procedure may generate invalid results. Author Response: The Thai version of the ZEF was translated using the forward and backward translation method and was examined for psychometric properties, including factor validity, convergent validity, internal consistency, and test-retest reliability, in our previous publication. We have added this sentence to the manuscript: “The Thai version of the ZEF was developed using forward and backward translation. The details and other psychometric properties are presented in Charoenporn and Charernboon (2023).” Reviewer Comment: 7. English language improvements are needed in some areas for an increase in readability and coherency. Author Response: We have rechecked and edited the manuscript with the help of our English speaker and ChatGPT-4. Thank you."
}
]
}
] | 1
|
https://f1000research.com/articles/13-617
|
https://f1000research.com/articles/11-365/v1
|
29 Mar 22
|
{
"type": "Research Article",
"title": "Views and practices on medical cannabis of unlicensed providers in Thailand: a qualitative study",
"authors": [
"Sawitri Assanangkornchai",
"Darika Saingam",
"Kanittha Thaikla",
"Muhammadfahmee Talek",
"Darika Saingam",
"Kanittha Thaikla",
"Muhammadfahmee Talek"
],
"abstract": "Background: Despite the legalization of cannabis use for medical purposes in Thailand in February 2019, illicit providers are still widespread and accessible. This study aimed to understand why people still chose to receive medical cannabis treatment or products from unlicensed or illegal providers. The practices of unlicensed or illegal providers in provision of medical cannabis products or treatment services were also examined. Methods: Qualitative in-depth interviews were conducted among medical cannabis providers and users, including 36 unlicensed and 7 licensed providers and 25 users in 2019-2021. Snowball sampling was used to recruit participants until saturation of data was achieved. Interviews included open-ended questions about the providers’ practices and attitudes towards medical cannabis. Interviews were recorded and transcribed, and thematic analysis was performed. Results: Overall, six reasons were identified to answer why unlicensed/illicit providers were still popular, including: 1) easy accessibility; 2) familiarity with the unlicensed providers before the legal scheme became available; 3) favorable characters (kind, supportive, non-judgmental) of unlicensed providers; 4) affordable treatment fees; 5) trust in the quality of the medicines; and 6) lack of knowledge and negative attitudes towards cannabis from healthcare professionals. Most providers started their career as medical cannabis providers by using it themselves or with their relatives and being satisfied with the results. They used cannabis products to treat all diseases, including skin, eyes, HIV/AIDS, non-communicable diseases and all kinds of cancers. Additionally, they believed that it was effective, with no or minimal adverse effects. Conclusions: This study suggests that some patients will continue receiving medical cannabis treatment and products from unlicensed or illegal providers. More attention should be paid on increasing the capacity of medical cannabis service systems within public health hospitals, and the certification of unlicensed providers, so as to integrate them into a regulated system.",
"keywords": [
"Medical cannabis",
"illegal providers",
"prescription practice",
"in-depth interview",
"legalization",
"decriminalization",
"thematic analysis",
"folk healers"
],
"content": "Introduction\n\nLegality of cannabis use in Thailand has undergone notable changes in recent years. Medical use of cannabis was legalized in February 2019. Nonetheless, cannabis remained an illegal drug until it was recently delisted in the newly amended Narcotics Code which went into effect on December 10th, 2021. On January 25th, 2022, the Narcotics Control Board approved the removal of parts of cannabis plant with no more than 0.2% tetrahydrocannabinol (THC) by weight from the Food and Drug Administration’s list of controlled drugs. The decision was approved by Parliament, and the Public Health Minister then signed the announcement of the delisting, which would take effect 120 days after the announcement was published in the government gazette.\n\nAfter the legalization of cannabis use for medical purpose, medical cannabis clinics, based on modern medicine and Thai traditional medicine, were piloted in government hospitals in August to September 2019, and scaled-up nationwide in 2020. Licensed healthcare practitioners, including medical doctors, dentists, Thai traditional medicine doctors, and folk doctors can prescribe medical cannabis products, which are registered under the Special Access Scheme (SAS). Three groups of medical cannabis products have been approved for medical use: 1) registered drugs per the new Narcotics Act; 2) Thai traditional medicine with approved compositions (16 regimens), and 3) folk-doctor cannabis oil. Despite this scale up of medical cannabis clinics, access to registered products for patients had been difficult as indications for prescription were limited and regulations regarding possession as well as production of medical cannabis were constricted. However, illicit cannabis trade from illegal medical cannabis suppliers, recreational dealers, and online suppliers, also became widespread and more accessible during this period.1\n\nPrevious studies have shown that people use medical cannabis for a variety of health conditions, such as pain, mental health and sleep problems and through its use felt relief of their condition.2–4 A study in Australia, in the early phase after legalization, indicated that the main sources of supply of medical cannabis were from recreational dealers, friends or family, illicit medicinal cannabis and online suppliers, and by growing their own.2 Furthermore, studies in Canada5 and the United States of America (USA),6 where medical cannabis is legally available, indicated that physicians felt reluctance or ambivalent to authorize cannabis use for their patients, because of either a lack of knowledge or unfamiliarity with pharmacology, formulations, dosing of cannabis, lack of product standardization, lack of research examining the effectiveness and risks of cannabis use, and uncertainty regarding the policies.\n\nTo date, no study has examined the views and practices of illicit providers of medical cannabis in Thailand. With an increasing demand of medical cannabis products amidst the restricted access to legal supply in Thailand, unlicensed medical cannabis providers and illegal suppliers come into play as an available source of medical cannabis products. Our study, conducted during the first year after the legalization of medical cannabis use in Thailand, found that 74% of the medical cannabis products used came from illegal sources, such as underground traders, not-for-profit provider groups (for example: priests, folk healers and civil society advocacy groups), friends and relatives, and home or clandestine growers and producers.7 In this study we aimed to understand why people still chose to receive treatment or medical cannabis products from unlicensed or illegal providers, despite licensed medical cannabis clinics in hospitals under the Ministry of Public Health (MoPH) having been opened nationwide since late 2019. We also examined the practices of unlicensed or illegal providers in provision of medical cannabis products or treatment services. In addition, this study examined the perspectives of medical cannabis users with regards to their access, perceived benefits and risks, and satisfaction towards those providers. Information obtained from this study could benefit the medical cannabis health care system in Thailand and other countries that have planned to, or have already initiated, medical cannabis policies. It will help in planning strategies to improve the capacity of said providers, and their services as well as improve access to medical cannabis.\n\n\nMethods\n\nThis study is a part of a larger two-phase study; using a mixed-method approach among medical cannabis users and providers in Thailand. The phase-1 study was conducted between October 2019 and February 2020; the first year of the medical cannabis legalization, followed by phase-2 between November 2020 and February 2021. Both phases comprised of a quantitative cross-sectional study, using respondent-driven sampling among medical cannabis users, and a descriptive qualitative approach involving in-depth interview of medical cannabis providers and users and observation of the providers’ practices and their medicines. Data of the qualitative part of both phases were used for thematic analysis. The descriptive qualitative approach, often used to discover the nature of the specific events under study, allows for a comprehensive summarization of views and practices of illegal providers and their services experienced by medical cannabis users, a topic about which little is currently known.8\n\nWe included 36 medical cannabis providers, who had not been certified by the MoPH as licensed folk doctors in this study. They included 15 folk healers, 9 growers or clandestine producers, who also provided treatment and counseling on using their products, and 12 workers of civil society networks or social media administrators that provided medical cannabis products and advice. Folk healers wishing to get prescription licenses need to be certified by the head of the provincial public health office or the Department of Thai Traditional Medicine and Alternative Medicine of the Ministry of Public Health. Those that meet the following criteria can be nominated by the village committee or local administrative organization for certification: aged at least 35 years, living in the community where the nomination takes place for more than 10 years, having knowledge and competence in promoting and caring for the health of people in the community using Thai traditional medicine wisdom according to their community culture for more than 10 years with admiration of the people in that community, being sane of mind and never having been incarcerated. Although, some of our participants had been practicing as folk healers for many years, they had not been certified; due to inadequate eligibility criteria or they just did not want to; said participants were recruited as unlicensed providers. Participants were eligible for the study if they were aged 18 years or over and willing to participate in the study. Exclusion criteria were set as being intoxicated, cognitively or mentally impaired, or too ill to be interviewed. However, we did not exclude any subject because of any of these reasons.\n\nPurposive sampling was used to recruit participants. First, some key informants, e.g., folk healers who practiced in the community and workers in non-government cannabis advocacy organizations were identified. These informants were then asked to provide contact information of other providers, which could be approached for an interview. In addition, some medical cannabis users, participating in this research, also provided us with the contact information of their providers.\n\nIn addition, seven licensed providers, including five medical doctors and two Thai traditional and alternative medicine doctors were also interviewed. Further, 25 medical cannabis users were recruited through snowball sampling, starting from some well networked individuals who were known by the researchers as being medical cannabis users. Participants were recruited until enough participants had been interviewed to achieve saturation of data.9\n\nParticipants were first contacted by telephone and invited to participate in the study. Each of four research assistants, who were at least bachelor’s degree graduates with previous experience in qualitative data collection with people who use drugs or people living with HIV in our other research projects, together with DS, KT or MT, who were experienced qualitative researchers, then visited the participants at a location set by them, e.g., home or workplace, and conducted the interviews.\n\nBefore the interview, verbal informed consent was obtained, and all interviews were audio recorded. At the times of data collection, most providers and consumers of medical cannabis were considered illegal, the use of written consent form might be perceived by participants to be threatening and treated with considerable skepticism by some participants. Signed informed consent form is the only record linking the subject and the research, and the principal risk would be potential harm resulting from a breach in confidentiality. To ensure the anonymity of participants, eliminating the risk that signatures could be linked to responses, verbal informed consent was obtained before the interview. In addition, the interview involved no more than minimal risk to subjects; therefore, the waiver of document of consent did not affect the rights and welfare of the subjects. Our Institutional Review Board thus waived the requirement for documentation of informed consent and allowed for verbal informed consent for both phases of the study.\n\nThe interviewers also made notes on nonverbal communications, which were used to supplement the audio-recorded information during transcriptions to ensure extensiveness of data. The interview was conducted in private and took up to one hour. Some follow-up interviews were also conducted for participants whose data from the initial interview were not complete, or when more clarification was required. The interview guide with open-ended questions and themes developed by the research team was used. We first tested questions included in the interview guide with some medical cannabis providers, such as two folk healers and two staff of not-for-profit medical cannabis organizations, and two users of medical cannabis. The guide covers content on the participants’ practicing experiences in providing, producing or using medical cannabis, source of cannabis, knowledge regarding diseases treated with cannabis, how they obtained this knowledge, and opinions towards medical cannabis laws and policies in Thailand. The guides can be found as Extended data.19 DS, KT and MT participated in the interviews and supervised the process of data collection and data transcriptions.\n\nAll interviews were transcribed verbatim by the research assistant who did the interview. DS, KT and MT also listened to some randomly selected interview recordings while reading through the respective transcribed data and field notes to ensure completeness and accuracy of the transcriptions. Qualitative data analysis was conducted manually. DS and SA then read the interview transcripts and notes repetitively, coded and aggregated transcribed text into meaningful themes and subthemes. The other members of the research team then read and discussed initial themes and subthemes until agreement was reached. For each subtheme, supporting quotes were selected to illustrate key points in the findings.\n\nBoth study phases were approved by the Research Ethics Committee (REC) of Faculty of Medicine, Prince of Songkla University [REC.62-205-18-1, dated 7 October 2019] and [REC.63-449-18-1, dated 3 December 2020]. The approval of the waiver of written consent was also documented in the REC approval documents.\n\n\nResults\n\nAltogether, 36 unlicensed or illegal providers, 7 licensed providers and 25 users participated in the study. Some participants initially refused or were reluctant to be interviewed; however, after having been given a detailed explanation of the study, including objectives and confidentiality safeguards by key informants in their community, all agreed to participate. The unlicensed provider sample included 34 men and 2 women, who had been involved in medical cannabis provision for a median of 50 years (range 25-85 years). Three of them were Buddhist monks. The users were 14 men and 11 women, whose age ranged between 32 and 80 years, and had been using medical cannabis for treatment for a variety of conditions, such as cancer, hypertension, migraines, insomnia and stress for a period of 2-10 years.\n\nOverall, six main reasons were identified for people choosing unlicensed providers and products: 1) easy accessibility to unlicensed or illegal sources; 2) familiarity with the unlicensed providers; 3) favorable characters of the providers; 4) affordable treatment fees; 5) trust in the quality of the medicines; and 6) a lack of knowledge, confidence and negative attitudes towards cannabis from healthcare professionals.\n\nEasy accessibility. Although medical cannabis clinics have been opened nationwide indications for treatment with medical cannabis oil extracts are limited, and accessibility has been poor and slow. Therefore, unlicensed or underground providers, who were more easily accessible, became their best available choice. Folk healers usually opened their practice within their own home where patients could visit them anytime without prior appointment. Some providers allowed their patients to contact them by Line application or telephone for consultation concerning health problems and medication adjustment; making patients feel supported and confident. Some even provided home visits or home delivery of medicine to their patients with limited mobility, such as the elderly or those with physical disabilities.\n\nSome patients cannot come by themselves, so they ask their children or caretakers to fetch medicines for them. They can come any day, or at their convenience. Some patients could not come up to my cubicle, so I went down to see them in their cars. When patients or their relatives come, we never refuse to see them or tell them to go home; even when their conditions are beyond treatment. (FD01)\n\nSome hospitals limited the number of patients to as little as 5 per day, and they are not open every day; maybe even only one day per week. (FD02)\n\nAfter five weeks of the clinic opening, we have seen 127 patients; however, only 48 cases have received cannabis medicine, because the others did not fulfil the indications. Many came because of insomnia, which does not fit the indication. Most have cancers; for example, lung, stomach and colon, with metastasis to other organs, but they are still in stage 3 which is not an indication; so, we cannot give them cannabis. The others have Parkinson and Alzheimer, for which they cannot receive cannabis oil either, because we have only THC oil. (MD01)\n\nI know I can get cannabis oil from the hospital, but I don’t want to go to the hospital. Going to a hospital is complicated. (PT01)\n\nFamiliarity. In some areas, folk healers had been well-known and accepted long before the boom of medical cannabis use in modern society. Using cannabis plants in folk and traditional medicine regimens has been regarded as ancient Thai wisdom. These folk healers, therefore, had already had follow-up with their patients for many years, and these patients preferred to continue treatment with their respectful and trustful doctors, rather than changing to new doctors in MoPH hospitals.\n\nMost of my patients are local people living in this village, so we meet when we make merit at the temple regularly. I visit my patients at home every week. I do it as a routine. For some families I take care of the whole family. (FD03)\n\nI am confident and trusting in … (a popular provider in the area)’s cannabis oil. I have been using it for more than one year. I have had migraines for 20-30 years. I had used medicines obtained from the hospital for several years, but they did not work. Two weeks after I took cannabis oil, I felt better so I continue using it. Why should I waste my time and pay bus and ferry fees to go to the hospital, while I can just ride a motorcycle or call …’s team to deliver the oil for me? (PT03)\n\nProviders’ characters. The folk healers that were interviewed appeared to be natural counselors, who understood and empathized with their clients’ illness and suffering. They were volunteer-minded and had the same goal as that of to help people. Patients also found the folk healers to be non-judgmental and non-stigmatizing. Almost all folk healers did not record their patients’ information systematically and did not make follow-up appointments with their patients. They just memorized the information and told patients to come back as needed, or they visited their patients at home when convenient. This surprisingly made patients more comfortable, as their information was confidential.\n\nWhy patients are getting well is not only because of the medicines, but it is also the conversations between patient and provider. It is a positive energy. They can talk with us through the chat box. We cheer them up and encourage them to fight the disease (NGO01).\n\nI never record patients’ information, and never give patients’ information to anyone. They trust me and can call me anytime. Some relatives call me late at night; telling me that the patient cannot tolerate anymore. I encourage them and tell them to come in to take cannabis oil. (FD03)\n\nHe (a respectful monk) is very kind. He always asks about my symptoms and if I have any side effects of chemotherapy after using cannabis oil. He advises me about diet, selfcare and teaches me some dharma (Buddhist teachings) too. (PT04)\n\nHe (a cannabis oil producer) visits me regularly, brings me the cannabis oil and some snacks. He knows that I live by myself, so he comes very often. When I got sick, he is the one who took care of me. I feel happy, laughing and not stressed when he comes. (PT05)\n\nFolk doctors never refuse us. They are always ready to give help and good advice for us to fight. (PT06)\n\nAffordability. Some folk healers - for example, Buddhist monks and those working in some civil society not-for-profit organizations - provided medical cannabis products free of charge for those who could not afford to pay. Folk healers who have been practicing in a conventional way do not usually ask for treatment fees; they accept only a “teacher worship fee”, which is very small. Although medical cannabis treatment in the MoPH hospitals was also free, as it was covered under the universal coverage or other medical insurance schemes, patients had to pay the transportation fee by themselves. Additionally, at the time of data collection of this work, MoPH medical cannabis clinics had yet been opened in every province, so some patients had to travel far to receive treatment. Nonetheless, some unlicensed providers charged for their products and treatment cost was very high; especially those who advertised their services and products through social media.\n\nOur center provides free cannabis oil to both Thai and foreign patients, regardless of their sex, age and socioeconomic status. We send free cannabis oil to every patient’s home and follow them up. … We make a sticker to put on the products that they are free, not for sale and that it is from a not-for-profit organization. Some foreign patients who received treatment from us and were impressed with it donated some money to our foundation, or sent product containers to us depending on their convenience. (NGO02)\n\nI teach patients and their relatives to make their own cannabis medicine. I told them to secretly grow 2-3 plants and produce their own medicine. I just give advice and follow their symptoms. I cannot take money from them because I don’t buy cannabis. (FD03)\n\nI don’t buy cannabis as my friends who grows it gives it to me. Folk doctors exchange their products; for example, I gave my colleagues some herbs that they don’t have to trade with cannabis. We don’t put money value on our herbs. (FD04)\n\nQuality of the medicines. Some patients believed that the medical cannabis oil extract provided from the MoPH hospital was too low in concentration (say, 1.7%) of active ingredients to be effective, while the oil extract from unlicensed sources was of better quality and could treat more diseases. Most conventional folk healers used the parts of raw plants to make their medicine mixture or extracted the crude oil in their home-kitchen. They may also grow, or suggest patients grow their own cannabis plants, to assure quality, and to keep the plants free from contamination. However, some patients as well as providers also worried about the quality of the illegal products as their sources were unknown, so they might be contaminated, and the production process might neither be so qualified.\n\nI tested cannabis medicine from the Government Pharmaceutical Organization. I think it’s not good. I think I make better products than those of the government hospitals, because I extract it by myself to treat my patients. I tailor make the medicine to the severity of the patients’ conditions. (FD03)\n\nNow underground products are of premium grade. Their production technique has gone so far, there are many talented chemists who have ever lived overseas. They want to make it known that the best formula is not what produced by the governmental people. We (underground producers) import extraction machines from China and Switzerland and secretly sent the extracts to some university professors to qualify them. (NGO03)\n\nHow can we deal with the underground dealers? Some sell fake oil which has no medicinal content at all. (FD03)\n\nI am confident in … … (a popular provider in the area), because he extracts it in an organic way. (PT03)\n\nHealthcare providers’ lack of knowledge and negative attitudes. One of the main reasons for medical cannabis being limited in prescriptions at public hospitals was due to the clinicians’ attitudes coupled with their readiness to provide it. Although medical cannabis training courses have been organized for doctors, pharmacists and other healthcare professionals to provide knowledge and grant certification for prescribing medical cannabis since the legalization, not many practitioners attended the courses; hence, most clinicians were not well enough prepared for medical cannabis practice. The general attitudes of medical professionals; in particular psychiatrists and pharmacists, were negative, due to concerns over adverse effects of mental health from cannabis use. Additionally, they were of the opinion that safer and more evidence-based medicines were already available for any indications wherein cannabis was to be used. Most medical professionals learn to practice medicine based on scientific evidence and from what they learn in medical schools. However, medical cannabis was new for them and supporting evidence was still limited, while conflicting evidence of benefits and harms was abundant. They were thus reluctant to prescribe medical cannabis. Moreover, there were strict regulations to follow and many forms to fill out when prescribing cannabis; medical cannabis prescription in a public hospital was still very restricted. An experienced and licensed doctor, who supported medical cannabis, expressed that medical professional might be the one who referred patients to the unlicensed or illegal system, because they refused to learn and prepare themselves to prescribe medical cannabis; despite their full awareness that their patients were using it.\n\nIn our hospital, pharmacists and psychiatrists don’t agree with medical cannabis use. … I think it’s not evidence that makes the resistance, but it’s the mindset. (MD01)\n\nWe, medical doctors have no right to refuse medical cannabis. We know that our patients use it. If we don’t learn and become aware of it, it means we don’t care for the patients and let them use it without our advice. Now we don’t even know if cannabis is good or bad, but if we refuse to learn and prescribe medical cannabis, it means we push our patients towards the underground system. (MD02)\n\nPreviously we have learned how to treat other diseases from what we learned in the university. However, for this issue (medical cannabis prescription) we have to learn it by ourselves, and start using it on our own; based on very limited evidence and a two-day training course. (MD03)\n\nSix subthemes were derived, including: 1) how they started their career as medical cannabis providers; 2) roles of the providers; 3) health conditions for which medical cannabis was used; 4) types of products and dosing; 5) use of modern medicine while using cannabis; and 6) progression of illness after treatment with cannabis.\n\nStarting the career. Most providers started their role as medical cannabis service providers from using cannabis as a self-medication for their or their relative’s health problems. After success in treating themselves or their relatives, they felt confident in using cannabis for other people. Some providers were full of interest and enthusiasm in acquiring knowledge on medical cannabis obtained from international published literature, social media, training courses and actual case studies. Moreover, cannabis has been a medicinal herb in Thai traditional medicine pharmacopeia since ancient times. Folk healers have acquired knowledge regarding medical cannabis from their ancestors, who were often folk healers as well. Therefore, folk healers were knowledgeable and experienced in medical cannabis treatment long before the start of medical cannabis within modern healthcare systems.\n\nThe origin of my work as a medical cannabis provider was because my mother got sick and could not walk. So, I trained from Mr. … (a famous unlicensed provider) and also took a Cannabinoid Medicine Training Course. I started using it with my mom and was very satisfied with the results; my mother can walk again. People are confident in me and ask me to provide treatment for them. (NGO04)\n\nAt that time there was a social trend that cannabis is a cancer medicine, I sought some information and photocopied the documents to give to my patients and relatives. Firstly, my close relative was sick and had to take a handful of medicines each day. I thought that in not so long his liver and kidney would be damaged, so I told him to try cannabis oil. He got better, blood pressure and sugar decreased. So, after that I advised other people in the area to find good quality cannabis products to treat their diseases. (FD03)\n\nI have to try it with myself before using it with my patients, because all cannabis plants are different. (FD06)\n\nCannabis oil is new in modern medicine, but traditional medicine has used it for a long time. All folk doctors know that cannabis is a kind of medicine and use it as an ingredient in several types of medicine; for example: “Happy sleep” regimen helping in sleep and appetite, “Santhakart” relieving constipation. I have cooked these regimens for a long time. (FD07)\n\nProviders’ roles. The providers had varied roles, including providing assessment, treatment and counseling as folk doctors, providing knowledge concerning medical cannabis summarized from published literature, being active advocators for legalizing cannabis, and growing, producing and selling medical cannabis products. Buddhist monks played active roles in not only being a spiritual center for local people, but also providing holistic care to patients, from the beginning to the terminal phase of illness; especially those classified as beyond available conventional treatment. Some providers believed that anyone could be a medical cannabis provider, if they cared about people and continued acquiring knowledge about diseases, by learning from research documents and by observing patients’ symptoms and progression.\n\nMy role is not only a monk who provides spiritual guidance, but also a doctor, pharmacist and counsellor. Patients can telephone me anytime. I advise them to follow religious principles to pray and be mindful on breathing, not to be too worried about the illnesses; as birth, aging, illness and death are a common truth. We encourage them to fight and find something to do. We should think that we are better than many people and well taken care of by our children. (FD05)\n\nAfter seeing a lot of patients, we would know why they do not respond to treatment, know if they use it in a correct way and have the discipline in taking care of themselves. We do not have to be a folk doctor or know everything like a medical doctor. We just know what should or should not be eaten, and that all diseases have different symptoms and stages; then adjust the dosages to best suit the patient’s current condition. (NGO05)\n\nHealth conditions. The health conditions for which cannabis was prescribed by folk healers included: cancers of various organs, Parkinson’s disease, epilepsy, muscle aches, headaches, insomnia, stress, depression, nausea, vomiting, psoriasis, acnes, ringworm, hemorrhoid, diabetes, hypertension, gout, HIV, and as a substitute for other drugs of abuse (methamphetamine and crystal methamphetamine). Terminal stage cancers, such as breast and brain cancers were the most common diseases patients sought out for cannabis treatment; especially when they were beyond available modern treatment or when they were to receive chemotherapy or radiotherapy. Their perception was that cannabis would help prepare the body to tolerate the side effects of such modern treatments. Most providers and their clients believed that cannabis could treat all diseases. Some providers indicated that cannabis balanced the system inside human body and could help relieve all symptoms that patients were suffering, for example: pain, fatigue, low appetite and sleep difficulty. If patients improved from these symptoms they would feel well and have the energy to fight the disease.\n\nCannabis can treat all diseases; it is the God of all medical herbs. (FD07)\n\nCannabis can treat almost all diseases, say more than 80 diseases. It can also be mixed with many herbal medicine regimens to help patients to get rest and repair their body. Cannabis is a repairer to help us sleep soundly. (FD04)\n\nCannabis oil will control cancer cells, so as they do not proliferate. (FD03)\n\nCannabis has several benefits, especially effects on the nervous system, helping with sleep, dementia and Parkinson, etc. (FD04)\n\nI think it (cannabis) helps balance the body. It does not treat a disease but gives immunity to us. Whatever disease we have, if our body is good, it will treat itself. Cannabis helps release a happiness agent, this agent then kills all diseases or suffering agents. Any medicine which makes us happy will balance our body system to fight a disease. (FD09)\n\nProducts and dosing. The products forms were various, such as extract oil in liquid form for sublingual administration or in a capsule for swallowing or for rectal suppository, tea made from dried raw plants which was claimed to be a good remedy for insomnia, topical skin cream and soap for skin diseases, toothpaste for toothache and caries, and a mixture bolus of the cannabis plant with other Thai herbs. Some folk healers also prescribed dried plants for smoking. Information related to product forms, route of administration, actions, dosing and sources is widely available on the Internet, through social media and word of mouth, for both providers and patients to learn and adaption of use for themselves, or when prescribing to others.\n\nSome healers advised their clients to start off with a test dose of one small drop of extract oil. If there was no sign of an allergic reaction, the users were advised to step up the dosage slowly until they found a suitable dose for themselves. They were then advised to maintain that dose until their symptoms subsided, then decrease the dose and finally stop when the symptoms disappeared. Females were advised to take a smaller dose than males. Morning and/or bedtime doses were usually recommended. Most providers emphasized that their clients should not take a second dose of oral extract oil within four hours after their first dose. They said that the action of the oral form was slow: approximately 30 minutes; therefore, if the second dose was taken shortly after the first dose their clients could easily get intoxicated. However, in a smoked form it was fast acting; approximately 5-15 minutes; thus, it was recommended for cases of cancer or severe stress, and for those who had pains or sleep difficulties.\n\nEach body is different. They should try it by themselves, so as to find out how much is suitable for them by measuring from their sleep. If it is too small, we cannot sleep then we can increase the dose; if it’s too much, intoxication will occur, so we should decrease the dose. (FD08)\n\nCapsules work with the enzyme system and is good for patients with colon cancer and cancers of the organs of the lower part of the body, such as prostate and ovarian cancers. For brain cancer, I recommend the smoking form with oil extract as cannabinoid glands are in this area. (NGO02)\n\nVaginal cancer patients should use a suppository form before having chemo or radiotherapy. Rectal suppository is good as it is not intoxicating and will revive our liver.\n\nUse of modern medicine. Most folk healers advised their patients to stop or reduce their dose of modern medicine which they had used before. They explained that modern medicine contained a lot of chemicals, causing imbalanced body function, and might impair liver and renal functions. However, some said cannabis and modern medicine should be used together, as cannabis would enhance the effects of modern medicine. Some folk healers viewed that terminally ill cancer patients who required morphine to relieve pain should receive supplementary cannabis, while tapering off morphine until stopping and then maintaining treatment with cannabis alone. Some folk doctors advised their patients to take cannabis and modern medicine at different times, so they would not interact with each other. Some even knew that cannabis was contraindicated for patients with cardiac arrythmia, bipolar mood disorders and those who used psychiatric medicines.\n\nI do not use modern medicine, because medical cannabis makes me feel better, healthier; so, I stopped modern medicine. Using too much modern medicine is not good for our liver and kidney. But it’s OK to use medical cannabis, even when we use too much there is less impact than from modern medicines. (NGO06)\n\nChemotherapy changes our tastebuds. Cannabis makes us feel sweater in the mouth and improves our tastebuds, so we can eat more. Cannabis should be taken along with chemo or radiotherapy. (FD02)\n\nI advise DM patients to not use cannabis oil with medicine received from the hospital. If they faint, they should stop either modern medicine or cannabis, because their blood sugar may drop too much as cannabis washes out sugar in our body. (FD03)\n\nPatients with irregular heartbeats cannot use cannabis. Bipolar patients and other psychiatric diseases should be careful too. If wanting to use medical cannabis it should be at a very low dosage, stop modern medicine or make a 2-3-hour interval between cannabis and modern medicine. (FD02)\n\nProgression of illness and side effects. After use of medical cannabis, most patients felt markedly better or cured, while some no longer returned to the hospital for treatment. The participants, either providers or users, believed that cannabis helped users to acquire deep sleep, an increase in appetite and a decreased pain, so the patients’ health and quality of life improved, their symptoms subsided, or their disease was cured. A number of folk doctors were aware of the negative health effects of cannabis; for example, intoxication when overdosing and toxicity when using low-quality products that were contaminated with insecticides or other toxic agents. However, most patients and folk doctors we interviewed had never experienced adverse effects of cannabis use by themselves.\n\nThe negative impact of cannabis is zero. I never see anyone with shock, death or progressive diseases because of cannabis. (FD03)\n\nPatients with skin diseases can use cannabis oil. Some who have whole body psoriasis get better after using cannabis oil, soap and cream for one month. Itching and lesions disappear. (FD03)\n\nThe obvious change I have seen is in cancer patients. Patients feel hopeful. People generally think that cancer patients must die, get chemo or radio. However, using cannabis, patients just stay happily at home and drop cannabis oil. This makes them feel more energetic. Cannabis activates the thought system in that they can survive. We advise them to use medical cannabis along with modern medicine. Cannabis is just an alternative. (NGO02)\n\n\nDiscussion\n\nOur paper provides insights on the experiences of folk healers and illegal providers in providing medical cannabis treatment. It was found that unlicensed providers were more popular than licensed practitioners in government medical cannabis clinics. Warmth, friendliness, supportiveness, non-judgmental attitudes and all-time accessibility, with free or low-cost treatment, made those folk healers or not-for-profit providers in this study well accepted by their patients. This led them to continue their practice, despite the availability of medical cannabis clinics in MoPH hospitals all over the country. The providers in this study used cannabis products to treat all diseases, such as skin, eyes, HIV/AIDS, and non-communicable diseases as well as all kinds of cancers. Additionally, it was believed that it was effective, with no or minimal adverse effects. They chose the product forms and dosages based on the patient’s symptoms, and some even tailor-made the medicine concentration to suit the patients’ condition. These findings mirror what was found from our cross-sectional studies among medical cannabis users, in that they sought medical cannabis products and treatment from illegal or unlicensed sources more than from the governments’ official medical cannabis clinics, and used cannabis for treatment of all diseases or symptoms.7\n\nStudies in Canada and the USA found that healthcare professionals felt reluctant and ambivalent in using cannabis for medical purposes, because of a lack of knowledge and concern about its adverse effects.5,6,10,11 However, our participants, both providers and patients, reported few or none of these concerns. The perception of medical cannabis as the last resort for those with terminal illness under limited access to modern healthcare systems determined a lack of concern. To our knowledge, there has not been a published study on attitudes and practices of medical doctors towards medical cannabis in Thailand. If it is similar to what was found in Canada and the USA, we could perceive that unlicensed or illegal providers could fill the gap of treatment for most patients of medical cannabis.\n\nSimilar to other studies,12–14 medical cannabis use was common among cancer patients. Both providers and patients in this study believed cannabis was good for the treatment of cancers, by alleviating pain, anorexia, nausea and sleep difficulty as well as improving body systems to tolerate modern treatment side effects; with few or no adverse effects being reported. Providers’ trustworthiness, caring attitude and easy accessibility were the main ingredients for these patients to adhere to their treatment and a feeling of improvement from their suffering. Thus, it is expected that many cancer patients - especially those in the terminal stage in Thailand - will turn to unlicensed or illegal medical cannabis providers, and cannabis use will continue to expand nationally. It has been unfortunately observed that many clinicians in the public healthcare system have limited knowledge concerning medical cannabis, and this results in patients turning to unlicensed providers who are willing to provide treatment. As such, our findings underline the need for oncologists or palliative care clinicians to be prepared to discuss with their patients regarding medical cannabis, or to recommend it clinically. Evidence to inform cancer treatment guidelines on potential benefits and harms of medical cannabis, matched with a Thai context is also required.\n\nOur study suggests that some patients will continue receiving medical cannabis treatment and products from unlicensed or illegal providers, despite licensed providers being available. This indicates the need to expand medical cannabis services in MoPH hospitals, and the requirement for reliable information for patients to access. The profusion of non-scientific information from websites, social media and community interaction reflects inadequate scientific information on efficacy and current healthcare service systems. However, increasing evidence of the benefits and safety of medical cannabis has appeared in international literature.15–18 Capacity development and certification of unlicensed providers, and a simplified version of correct scientific evidence for patients to understand the risks and benefits of use are imperative. As reported by the participants of this study, some underground cannabis businesses who produce and sell expensive, but poor-quality or fake products also exist. There needs to be a system to monitor and to control quality, price and safety of medical cannabis products sold in the market place, which will be most beneficial to users who need it. Only through evidence-based interventions in healthcare systems and clear public health policies of medical cannabis, can success in medical cannabis service provisions be ensured with best outcomes of safety and efficacy.\n\nOnly data from a limited number of medical cannabis providers and users were included. Although we recruited sample to saturation and stopped interviewing new participants when no additional themes emerged in our last interview, our sample might subject to volunteer bias as most of the respondents were positive towards medical cannabis use. This may have led them to report only the positive side of cannabis use, and the unlicensed or illegal services. Snowball sampling was used to reach the participants, so this might limit the participants to the group of those who had similar values towards medical cannabis, and overrepresent supporters of medical cannabis.\n\n\nConclusion\n\nUnlicensed or illegal medical cannabis providers were still, and tended to remain popular, in Thailand. Patients regarded them as a last, dependable and trustful resource under limited access to public healthcare systems. Significantly more attention should be paid on increasing the capacity of medical cannabis service systems within public health hospitals. Additionally, certification of unlicensed providers, so as to integrate them into a regulated system where quality assurance can be maintained, is required. Furthermore, clear scientific information should be disseminated to patients who require the use of cannabis for treatment of their illnesses.\n\n\nData availability\n\nThe interview transcripts cannot be shared publicly as they contain personal and sensitive information, which could identify the participants. The interview transcripts are all in Thai. Anyone wishing to read the summary report of the data, including quotes may contact the corresponding author (savitree.a@psu.ac.th), who will do translation of the parts requested.\n\nOpen Science Framework: Views and practices on medical cannabis of unlicensed providers in Thailand: a qualitative study. https://doi.org/10.17605/OSF.IO/PBRHJ.19\n\nThis project contains the following extended data:\n\n- Interview guide-providers.pdf\n\n- Interview guide-users.pdf\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "Acknowledgements\n\nWe would like to thank Mr. Andrew Tait, from the International Affairs Department, for English proofreading of the manuscripts.\n\n\nReferences\n\nCentre for Addiction Studies: A survey on knowledge, understanding and opinion of Thais aged 15 and over on medical and recreational use of cannabis. Songkhla: Centre for Addiction Studies, Epidemiology Unit, Faculty of Medicine, Prince of Songkla University; 2020; 126. Reference Source\n\nLintzeris N, Mills L, Suraev A, et al.: Medical cannabis use in the Australian community following introduction of legal access: the 2018-2019 Online Cross-Sectional Cannabis as Medicine Survey (CAMS-18). Harm Reduct. J. 2020; 17: 37. PubMed Abstract | Publisher Full Text\n\nLuque JS, Okere AN, Reyes-Ortiz CA, et al.: Mixed methods study of the potential therapeutic benefits from medical cannabis for patients in Florida. Complement. Ther. Med. 2021; 57: 102669. PubMed Abstract | Publisher Full Text\n\nSexton M, Cuttler C, Finnell JS, et al.: A cross-sectional survey of medical cannabis users: patterns of use and perceived efficacy. Cannabis Cannabinoid Res. 2016; 1: 131–138. PubMed Abstract | Publisher Full Text\n\nNg JY, Gilotra K, Usman S, et al.: Attitudes toward medical cannabis among family physicians practising in Ontario, Canada: a qualitative research study. CMAJ Open. 2021; 9: E342–E348. PubMed Abstract | Publisher Full Text\n\nChristensen VA, Nugent SM, Ayers CK, et al.: A qualitative study of VHA clinicians’ knowledge and perspectives on cannabis for medical purposes. Fam. Pr. 2021; 38: 479–483. PubMed Abstract | Publisher Full Text\n\nAssanangkornchai S, Thaikla K, Talek M, et al.: Medical cannabis use in Thailand after its legalization: a respondent-driven sample survey. PeerJ. 2022; 10: e12809. PubMed Abstract | Publisher Full Text\n\nLambert VA, Lambert CE: Qualitative Descriptive Research: An Acceptable Design. Pac. Rim. Int. J. Nurs. Res. 2013; 16: 255–256.\n\nAndo H, Cousins R, Young C: Achieving saturation in thematic analysis: development and refinement of a codebook. Compr Psychol. 2014; 3Publisher Full Text\n\nSzaflarski M, McGoldrick P, Currens L, et al.: Attitudes and knowledge about cannabis and cannabis-based therapies among US neurologists, nurses, and pharmacists. Epilepsy Behav. EB. 2020; 109: 107102. PubMed Abstract | Publisher Full Text\n\nBraun IM, Wright A, Peteet J, et al.: Medical oncologists’ beliefs, practices, and knowledge regarding marijuana used therapeutically: A nationally representative survey study. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2018; 36: 1957–1962. PubMed Abstract | Publisher Full Text\n\nMartell K, Fairchild A, LeGerrier B, et al.: Rates of cannabis use in patients with cancer. Curr. Oncol. 2018; 25: 219–225. PubMed Abstract | Publisher Full Text\n\nNielsen SW, Ruhlmann CH, Eckhoff L, et al.: Cannabis use among Danish patients with cancer: a cross-sectional survey of sociodemographic traits, quality of life, and patient experiences. Support Care Cancer. 2021; 30: 1181–1190. PubMed Abstract | Publisher Full Text\n\nPergam SA, Woodfield MC, Lee CM, et al.: Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use. Cancer. 2017; 123: 4488–4497. PubMed Abstract | Publisher Full Text\n\nTafelski S, Häuser W, Schäfer M: Efficacy, tolerability, and safety of cannabinoids for chemotherapy-induced nausea and vomiting--a systematic review of systematic reviews. Schmerz Berl Ger. 2016; 30: 14–24. PubMed Abstract | Publisher Full Text\n\nWhiting PF, Wolff RF, Deshpande S, et al.: Cannabinoids for medical use: A systematic review and meta-analysis. JAMA. 2015; 313: 2456–2473. Publisher Full Text\n\nAllan GM, Finley CR, Ton J, et al.: Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms. Can. Fam. Physician Med. Fam. Can. 2018; 64: e78–e94.\n\nBlack N, Stockings E, Campbell G, et al.: Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis. Lancet Psychiatry. 2019; 6: 995–1010. PubMed Abstract | Publisher Full Text\n\nAssanangkornchai S: Views and practices on medical cannabis of unlicensed providers in Thailand: a qualitative study.2022, March 15. Publisher Full Text"
}
|
[
{
"id": "202145",
"date": "03 Oct 2023",
"name": "Davide Fortin",
"expertise": [
"Reviewer Expertise Cannabis Policy and Economics",
"Health Economics",
"Industrial Organization",
"Cost-Effectiveness Analysis",
"Patient-Reported Outcomes"
],
"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\nREPORT \"Views and practices on medical cannabis of unlicensed providers in Thailand: a qualitative study\"\nIn a market which legalize the distribution of cannabis for medical purposes, the reason why patients still choose to buy cannabis illicitly is an interesting topic of research. In the article, the authors study this phenomenon during the first year after the legalization of ‘medical cannabis’ in Thailand. To do so, the authors perform interviews with medical cannabis providers and users. They identified six reasons behind the popularity of unlicensed provider, namely accessibility, familiarity with the providers prior to legalization, favourable character of the providers, affordability, quality and lack of knowledge towards cannabis from healthcare professionals.\nThe paper is written quite decently, and the way the healthcare system in Thailand has integrated medical cannabis through three different groups of products is of interest for other countries with similar approaches to traditional medicine.\nA major issue is that it does not highlight enough the fact that interviews were taken during the first year after the passage of the law, when not only healthcare system is unprepared to prescribe to patients, but also few products are available and those which are distributed are thus likely to be quite expensive. This affect both patients from using them and physicians to prescribe it when they are aware of cheaper options to treat the medical condition. To help readers to better understand the research context, this fact should be probably not only be included in the abstract, but also the reason of low affordability and accessibility should be the first mentioned behind the choice of patients to go to unlicensed providers.\nI have a few other concerns which I believe need some attention and would help improve the paper :\nIn the second paragraph, it is mentioned that “access to registered products for patients had been difficult as indications for prescription were limited and regulations regarding possession as well as production of medical cannabis were constricted.”. I think it should expanded to understand whether there is a limited number of medical conditions which allow the prescription of medical cannabis based on the existence of randomized clinical trials proving its efficacy. From the results, I understand insomnia is not consider a condition for the prescription, but the rationale behind which condition is accepted should be clearly identified in the text.\n\nIt is not clear whether one of the three types of medical cannabis products which can be prescribe include flowers (or inflorescence). If this is not the case, it should be clearly stated as this type of products is the most used among countries which legalize the medical use of cannabis (e.g. Canada, US). In parallel, it should be also clarified whether some of the unlicensed producers were selling flowers and/or resins, or if they are only selling non-smokable products (If they sell flowers, this should be another reason why they are popular, the fact that they have a different type of medical cannabis product).\n\nIn the third paragraph, the authors mention “Furthermore, studies in Canada and the United States of America (USA), where medical cannabis is legally available, indicated that physicians felt reluctance or ambivalent to authorize cannabis use for their patients, because of either a lack of knowledge or unfamiliarity with pharmacology, formulations, dosing of cannabis, lack of product standardization, lack of research examining the effectiveness and risks of cannabis use, and uncertainty regarding the policies.”. Considering the increased in research in recent years related to cannabis (Ng and Chang, 2022), the real issue relates to the lack of Randomized Clinical Trials (as this is normally what physicians use to base their decision) which are hampered from technical and economic barriers related to medical cannabis (Fortin and Massin, 2020). This should be clearly explained in the text.\n\nAbout the lack of knowledge from physicians, Hagani et al. (2021) should be included as it studied the gaps in perceptions toward MC between patients and health professionals.\n\nIn the literature, Fortin (2022) should be added as it models the competition between healthcare system and illicit market for medical cannabis and provide some additional solutions to reduce the number of patients who buy their treatment in the illicit market.\n\nWhen talking about the issue of low availability, Wadsworth et al. (2021) should be added as they show that retail availability was associated with last purchasing dried flower legally among past-year dried flower purchasers.\nOther points to be considered below:\nIn the second paragraph, they mention the first type of product saying “registered drugs per the new Narcotics Act”. I don’t think that the wording “per the” is grammatically correct.\n\nInstead of using the term “users”, the author should use the term “patients” given that we assume they are using cannabis for medical purposes.\n\nI think this sentence should be rephrased to be more easily understood :“The perception of medical cannabis as the last resort for those with terminal illness under limited access to modern healthcare systems determined a lack of concern.”\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?\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": "10378",
"date": "16 Nov 2023",
"name": "Sawitri Assanangkornchai",
"role": "Author Response",
"response": "Thank you for your valuable comments and suggestions. As suggested, we will add more information in the introduction part of the manuscript on the timing of the study and how it affected the health system, the availability of cannabis-based products, and physician prescription practice. A list of medical conditions approved by the Thai Ministry of Public Health for cannabis treatment and those with supported evidence of efficacy from randomized clinical trials will be added. We will also explain if cannabis flowers and resins were included in the prescribed and unlicensed medical cannabis products in the introduction and discussion parts. Furthermore, the references suggested by the reviewer will be cited to support the explanation and discussion of the related issues. Lastly, we will check the grammatical correctness and rephrase the unclear sentence."
}
]
}
] | 1
|
https://f1000research.com/articles/11-365
|
https://f1000research.com/articles/13-802/v1
|
16 Jul 24
|
{
"type": "Research Article",
"title": "Unraveling the genetic basis of antibiotic resistance in Staphylococcus aureus: Focus on mecA and PVL Genes",
"authors": [
"Be-Hai Nguyen-Thi",
"Ngoc-Nga Pham-Thi",
"Hai-Yen Nguyen-Thi",
"Long-Nguyen Nguyen",
"Trung-Son Le",
"Be-Hai Nguyen-Thi",
"Hai-Yen Nguyen-Thi",
"Long-Nguyen Nguyen",
"Trung-Son Le"
],
"abstract": "Background\n\nStaphylococcus aureus infections, including Methicillin-Resistant S. aureus (MRSA) and Methicillin-Sensitive S. aureus (MSSA), present significant challenges in healthcare due to rising antimicrobial resistance. This study evaluates the genetic basis of antibiotic resistance in S. aureus, focusing on key resistance-associated genes mecA and PVL.\n\nMethods A total of 568 clinical specimens were analyzed for the presence of S. aureus. Demographic data were collected to assess age-dependent prevalence. Antimicrobial susceptibility testing was conducted to evaluate resistance patterns. The prevalence of the mecA and PVL genes was determined using molecular techniques.\n\nResults\nS. aureus was identified in 37.9% of cases, with the highest prevalence (60-79 age group). All S. aureus isolates showed 100% resistance to penicillin. Multidrug-resistant (MDR) strains accounted for 84.19% of isolates, with a significant presence of extensively drug-resistant (XDR) strains. The mecA gene was prevalent in 82.79% of MRSA isolates, indicating its strong association with methicillin resistance. Additionally, 41.86% of all S. aureus isolates were positive for the PVL gene, highlighting its widespread distribution.\n\nConclusions The high prevalence of mecA and PVL genes in S. aureus strains underscores the challenges in managing these infections. These findings emphasize the necessity for judicious antibiotic use and enhanced collaborative efforts to combat antimicrobial resistance. Understanding the genetic basis of resistance can inform more effective diagnostic, therapeutic, and preventive strategies, ultimately improving patient outcomes in S. aureus infections.",
"keywords": [
"Antibiotic resistance",
"mecA",
"MRSA",
"PVL",
"Staphylococcus aureus"
],
"content": "Introduction\n\nStaphylococcus aureus presents in two major variants, Methicillin-Resistant S. aureus (MRSA) and Methicillin-Sensitive S. aureus (MSSA), each posing distinct challenges and requiring tailored approaches for management. MRSA, resilient against methicillin and diverse beta-lactam antibiotics, poses a significant global health threat, leading to severe complications and increased mortality within 48 hours of hospital admission (Chatterjee et al., 2018; Rubio-Garcia et al., 2023). Innovative treatment strategies, such as combining natural compounds with antibiotics, have been explored to enhance bactericidal efficacy and minimize side effects, focusing on preventing MRSA introduction and dissemination in healthcare and community settings (Al-Tawalbeh et al., 2023; Woźniak et al., 2024). Effective MRSA prevention necessitates the identification and control of risk factors, including prolonged surgery duration, extensive antibiotic use, and patient condition (Sun et al., 2024a).\n\nConversely, MSSA, susceptible to methicillin and other beta-lactam antibiotics, coexists with MRSA, demanding attention to different therapeutic considerations (Arif et al., 2024). While challenges arise from increasing antimicrobial resistance in MSSA, the primary focus remains on MRSA mitigation. Conventional beta-lactam agents, particularly cefazolin, have demonstrated efficacy, with considerations for central nervous system infections and reduced administration barriers compared to penicillins (Antosz et al., 2023). Persistent MSSA bacteremia complexities require source control and modified therapy, with combination therapy and recognition of the inoculum effect showing promise (Chastain et al., 2023). Strategies for MSSA prevention involve addressing resistance challenges in decolonization, utilizing agents like mupirocin, and employing rapid diagnostic tests for tailored treatment (Palavecino, 2020). The development of a protective vaccine holds potential to reduce morbidity and mortality associated with invasive MSSA disease, forming a comprehensive strategy against these pathogens (Cassat & Thomsen, 2021).\n\nThe research aims to evaluate the current status of antibiotic resistance in S. aureus, focusing on the key resistance-associated genes, mecA and PVL. The mecA gene, critical in methicillin resistance, plays a central role in the evolution of MRSA, rendering it resilient against beta-lactam antibiotics (John, 2020; Tasneem et al., 2022). Understanding the genetic organization of mecA, as emphasized by Abdullahi et al. (2023), is crucial in addressing multidrug resistance challenges, particularly in non-aureus staphylococci.\n\nPVL stands out as a virulence factor in S. aureus, significantly contributing to pathogenicity and rapid dissemination, especially in skin and soft tissue infections (Leistner et al., 2022; Tromp & van Strijp, 2020). The research will explore the role of PVL in the increased virulence and epidemic spread of S. aureus, aiming to unravel the exact mechanisms and contributions to the pathophysiology of this versatile bacterium. Diagnostic and therapeutic aspects related to PVL will be investigated, considering its association with recurrent skin infections and potential links to broader health issues, including cancer (Wei et al., 2022). The study endeavors to contribute to a comprehensive understanding of the impact of these key genes on S. aureus resistance and pathogenicity.\n\nMRSA and MSSA pose significant challenges in the control and prevention of S. aureus infections. While MRSA presents grave threats due to extensive antibiotic resistance, MSSA shows rising drug resistance. Key resistance and virulence genes such as mecA and PVL play pivotal roles in the evolution and pathogenicity of S. aureus. Further investigation into these genetic mechanisms will support diagnostic, therapeutic, and preventative strategies to effectively control MRSA.\n\n\nMethod\n\nS. aureus strains were isolated from clinical samples obtained from patients at Can Tho University of Medicine and Can Tho City General Hospital. The sampling process involved patients with S. aureus infections, and the bacterial isolates were identified using the Vitek system, following the methodology outlined by Tran et al. (2023).\n\nVarious types of clinical specimens were collected from different departments, including the Internal Medicine Department (IMD), Trauma Surgery Department (TSD), Surgical Department (SD), Outpatient Clinic Department (OCD), as well as other specialized departments such as Oncology Department (OD), Cardiology Department (CD), Nephrology and Urology Department (NUD), and External Medicine Department (EMD). The collected specimens encompassed pus, phlegm, fluid, and blood, providing a comprehensive representation of bacterial strains in diverse clinical conditions.\n\nThe sampling duration extended from April 2022 to April 2023, ensuring a year-long representation of S. aureus strains prevalent in the patient population during this period.\n\nAntimicrobial susceptibility testing of S. aureus isolates was facilitated utilizing the Vitek-2 Compact automated system (bioMérieux, USA). The AST-GN67 testing card (Catalog number: 413399; bioMérieux, USA) enabled efficient determination of minimum inhibitory concentrations for selected antibiotics based on CLSI breakpoints. CLSI, antibiotic susceptibility interpretation covered agents across categories, with details provided in Table 1. Isolates were classified by resistance patterns - multidrug-resistant (MDR), extensively drug-resistant (XDR) or pan-drug-resistant (PDR), applying standard definitions of non-susceptibility to one/three or more agents (Tran et al., 2023). This approach leveraging automated technology ensured rigorous evaluation of antibiotic resistance across S. aureus isolates within a streamlined workflow.\n\nThe mecA, and PVL genes were detected in all S. aureus isolates. Genomic DNA extraction from the cells was performed using the Invisorb® Spin Universal kit (Catalog number: 1050100300; Invitek Molecular, Germany) (Tran et al., 2023). PCR amplification was conducted using the MyTaq™ Red Mix Kit (Catalog number: BIO-25044; Meridian Bioscience, USA) and the C1000 Touch Thermal Cycler system (Bio-Rad, USA). The reaction mixture included specific primers for each gene, as detailed in Table 2 (Hsu et al., 2004; Le et al., 2021; Lee, 2003). The PCR amplification conditions comprised an initial denaturation step at 95°C for 3 minutes, followed by 40 cycles of amplification at 95°C for 30 seconds, 55°C for 30 seconds, and 72°C for 30 seconds. The final extension step was maintained at 72°C for 5 minutes.\n\nT-tests were used to compare mean differences between two groups, such as different testing methods. Analysis of Variance (ANOVA) was employed to assess differences among three or more groups, such as various testing methods. Additionally, multivariate analysis was utilized to evaluate relationships between multiple variables simultaneously. These methods ensured thorough analysis of the data and provided insights into the efficacy of different testing methods and correlations between variables.\n\n\nResult\n\nThe study involved the analysis of 568 clinical specimens, with the Vitek-2 Compact automated system used for automatic identification. Results from this identification process revealed the presence of 215 out of 568 isolates as S. aureus, constituting 37.9% of the total samples (p < 0.05). Additionally, E. coli and K. pneumoniae were identified at rates of 25.7% and 21.2% (p = 0.05).\n\nTo provide a demographic perspective, the age distribution of individuals with S. aureus infections is illustrated in Figure 1. The age range for male patients varied from 28 to 101 years, with a median age of 68 and a mean age of 67.78. On the other hand, female patients exhibited an age range from 20 to 102 years, with a median age of 67 and a mean age of 66.76. These findings offer insights into the age and gender distribution of individuals affected by S. aureus infections in the studied population (p > 0.05).\n\nAtl text: The age range for male patients varied from 28 to 101 years, with a median age of 68 and a mean age of 67.78. For female patients, the age range was from 20 to 102 years, with a median age of 67 and a mean age of 66.76. This figure provides insights into the age and gender distribution of individuals affected by S. aureus infections in the studied population (p > 0.05).\n\nFor the age group 20-39, the presence of S. aureus was observed in 5 males (2.33%) and 6 females (2.79%). In the 40-59 age group, the prevalence increased, with 27 males (12.56%) and 21 females (9.77%) testing positive for S. aureus (Figure 2). The age group 60-79 exhibited the highest prevalence, with 66 males (30.70%) and 42 females (19.53%) found to have S. aureus infections. Among individuals over 80 years old, 26 males (12.09%) and 22 females (10.23%) were identified with S. aureus (Figure 2). These results highlight an age-dependent pattern, with a notable increase in S. aureus prevalence in the older age groups, particularly in individuals aged 60-79. This information contributes valuable insights into the distribution of S. aureus infections across different age categories (p < 0.05), aiding in the understanding of demographic factors associated with susceptibility to these infections.\n\nAtl text: In the 20-39 age group, 5 males (2.33%) and 6 females (2.79%) were infected. In the 40-59 age group, the prevalence increased to 27 males (12.56%) and 21 females (9.77%). The 60-79 age group exhibited the highest prevalence with 66 males (30.70%) and 42 females (19.53%) infected. Among individuals over 80 years old, 26 males (12.09%) and 22 females (10.23%) were identified with S. aureus. These results show an age-dependent pattern, with a significant increase in prevalence in older age groups, especially those aged 60-79 (p < 0.05).\n\nFigure 3 illustrates the distribution of S. aureus detection across different illnesses, providing valuable insights into the prevalence of S. aureus in association with specific health conditions. The majority of cases, constituting 36.28%, showed no reported illness. This suggests that a considerable proportion of individuals without underlying health issues also experienced S. aureus infections. In contrast, diabetes mellitus emerged as a significant contributing factor, with 52.56% of cases associated with this condition. The prevalence of S. aureus in individuals with renal failure accounted for 6.05%, highlighting the relevance of kidney-related health concerns. Specific medical interventions, such as open surgery, were linked to 2.79% of S. aureus cases, emphasizing the potential risk within healthcare settings. Additionally, cancer was associated with 2.33% of cases, indicating the presence of S. aureus in individuals undergoing cancer-related treatments. This detailed breakdown of illness categories provides a nuanced understanding of the varied contexts in which S. aureus infections occur. The higher prevalence in diabetes mellitus cases underscores the importance of tailored strategies for infection prevention and management in individuals with specific underlying health conditions.\n\nAtl text: A substantial proportion of cases (36.28%) had no reported illness, while diabetes mellitus was associated with 52.56% of cases. Renal failure accounted for 6.05% of cases, open surgery for 2.79%, and cancer for 2.33%. This figure highlights the prevalence of S. aureus in association with specific health conditions, emphasizing the need for tailored infection prevention and management strategies in individuals with certain underlying conditions.\n\nFigure 4 presents an insightful analysis of the distribution of S. aureus detection concerning underlying health conditions. The data highlights the significance of the immunocompromised status in relation to S. aureus infections. Among the cases analyzed, 63.26% were associated with individuals classified as immunocompromised. This substantial proportion emphasizes the heightened vulnerability of individuals with compromised immune systems to S. aureus infections. It underscores the critical role of immune function in protecting against such bacterial infections. Conversely, 36.74% of cases were attributed to individuals categorized as non-immunocompromised. While this group represents a significant portion, the data underscores that S. aureus infections are not exclusive to immunocompromised individuals, as they also affect those with apparently normal immune function. The distinct division between immunocompromised and non-immunocompromised categories provides a clear understanding of the association between immune status and susceptibility to S. aureus infections (p > 0.05). This insight is crucial for tailoring preventive measures and treatment strategies based on the specific health conditions of individuals.\n\nAtl text: Among the analyzed cases, 63.26% were associated with immunocompromised individuals, indicating a heightened vulnerability to S. aureus infections. Conversely, 36.74% of cases were found in non-immunocompromised individuals. This figure emphasizes the significant role of immune function in susceptibility to S. aureus infections and the need for specific preventive measures for immunocompromised individuals (p > 0.05).\n\nFigure 5 provides a detailed breakdown of S. aureus detection across different departments within the hospital setting. The data sheds light on the prevalence of S. aureus in various medical departments, indicating potential areas of focus for infection control and preventive strategies. The Internal Medicine Department (IMD) exhibits the highest count of S. aureus cases, representing 39.53% of the total cases. This suggests a significant presence of S. aureus infections among patients seeking treatment in the Internal Medicine Department. The Trauma Surgery Department (TSD) follows closely with 20.93% of cases, emphasizing the relevance of S. aureus infections in patients undergoing trauma-related medical interventions. Surgical Department (SD) and Outpatient Clinic Department (OCD) contribute 16.28% and 15.81% to the total cases (p < 0.05), indicating a substantial presence of S. aureus in these departments. Additionally, there are 7.44% of cases categorized under “Other” departments, which may include specialty units such as Oncology, Cardiology, Nephrology and Urology, and External Medicine. This suggests a distributed occurrence of S. aureus infections in various specialized areas of the hospital. The department-wise analysis presented in Figure 5 enables healthcare professionals to target specific areas for heightened surveillance, infection prevention, and control measures tailored to the distinct characteristics of each medical department.\n\nAtl text: The Internal Medicine Department (IMD) exhibited the highest count of S. aureus cases (39.53%), followed by the Trauma Surgery Department (TSD) with 20.93%. The Surgical Department (SD) and Outpatient Clinic Department (OCD) accounted for 16.28% and 15.81% of cases, respectively (p < 0.05). An additional 7.44% of cases were categorized under \"Other\" departments, which include specialized units such as Oncology, Cardiology, Nephrology and Urology, and External Medicine. This department-wise analysis helps target specific areas for enhanced surveillance and infection control measures.\n\nFigure 6 illustrates the antimicrobial susceptibility patterns of S. aureus isolates across different antibiotic groups. The data provides insights into the prevalence of resistance, intermediate susceptibility, and susceptibility to various antibiotics commonly used in clinical settings.\n\nNote: R = Resistance, I = Intermediate susceptibility, S = Susceptibility. Atl text: The majority of S. aureus isolates exhibited 100% resistance to penicillin (PEN). Resistance rates varied for other beta-lactam antibiotics: cefoxitin (CFX) showed 81.86% resistance, oxacillin (OXA) 60.46%, and amoxicillin-clavulanate (MOX) 33.48% (p < 0.05). No intermediate susceptibility was observed for beta-lactam antibiotics. For macrolides, high resistance was noted: azithromycin (AZM) at 86.04% and erythromycin (ERY) at 86.97% (p < 0.05). Among peptid antibiotics, linezolid (LNZ) had the highest susceptibility at 86.05%, while tetracycline (TCY) and vancomycin (VAN) showed resistance rates of 55.81% and 7.91%, respectively (p < 0.05). In the quinolone group, ciprofloxacin (CIP) and levofloxacin (LVX) had resistance rates of 48.37% and 49.3%, with sulfamethoxazole-trimethoprim (SXT) showing 54.41% resistance (p < 0.05). Other antibiotics showed varying resistance rates: rifampicin (RIF) at 6.05%, gentamicin (GEN) at 58.6%, and clindamycin (CLI) at 80% (p < 0.05). The data underscores widespread resistance to multiple antibiotic classes, emphasizing the need for careful antibiotic use and ongoing resistance monitoring.\n\nFor beta-lactam antibiotics, the majority of S. aureus isolates exhibited resistance to penicillin (PEN), with 100% resistance observed. Resistance rates to other beta-lactam antibiotics varied, with cefoxitin (CFX) showing 81.86% resistance, oxacillin (OXA) 60.46% resistance, and amoxicillin-clavulanate (MOX) 33.48% resistance (p < 0.05). Intermediate susceptibility was not observed for any of the beta-lactam antibiotics tested.\n\nIn the macrolide group, S. aureus isolates showed high resistance to azithromycin (AZM) at 86.04% and erythromycin (ERY) at 86.97%. Intermediate susceptibility was minimal, while susceptibility rates were relatively low for both antibiotics (p < 0.05).\n\nAmong the peptid antibiotics, linezolid (LNZ) demonstrated the highest susceptibility, with 86.05% of isolates being susceptible. Resistance rates were notable for tetracycline (TCY) at 55.81% and vancomycin (VAN) at 7.91%, with intermediate susceptibility observed for both antibiotics (p < 0.05).\n\nIn the quinolone group, ciprofloxacin (CIP) and levofloxacin (LVX) exhibited comparable resistance rates, with 48.37% and 49.3% resistance. Sulfamethoxazole-trimethoprim (SXT) showed resistance in 54.41% of isolates. Intermediate susceptibility was observed for some isolates across these antibiotics (p < 0.05).\n\nFor other antibiotics, rifampicin (RIF) displayed resistance in 6.05% of isolates, while gentamicin (GEN) and clindamycin (CLI) exhibited resistance rates of 58.6% and 80%, respectively. Intermediate susceptibility was noted for rifampicin, gentamicin, and clindamycin, with varying proportions (p < 0.05).\n\nOverall, the data underscores the widespread resistance of S. aureus isolates to multiple classes of antibiotics, emphasizing the importance of judicious antibiotic use and surveillance to combat antimicrobial resistance.\n\nFigure 7 depicts the distribution of resistance patterns among S. aureus isolates. The data reveals three main resistance patterns: multidrug-resistant (MDR), extensively drug-resistant (XDR), and non-resistant. Multidrug-resistant (MDR) strains constitute the majority, with 181 isolates, accounting for 84.19% of the total. These strains exhibit resistance to antibiotics from multiple classes, posing significant challenges in treatment selection. Extensively drug-resistant (XDR) strains, characterized by resistance to most available antibiotics except a few, are observed in 10 isolates, representing 4.65% of the total. XDR strains present even greater therapeutic challenges due to limited effective treatment options. Non-resistant strains, comprising 24 isolates (11.16%), are susceptible to the antibiotics tested in this study (p < 0.05). While these strains are susceptible to antimicrobial agents, monitoring their susceptibility patterns remains crucial to prevent the emergence of resistance.\n\nAtl text: The data reveals three main resistance patterns: multidrug-resistant (MDR), extensively drug-resistant (XDR), and non-resistant. MDR strains constituted the majority with 181 isolates (84.19%), showing resistance to multiple antibiotic classes. XDR strains, resistant to most antibiotics except a few, accounted for 10 isolates (4.65%), presenting significant treatment challenges. Non-resistant strains, comprising 24 isolates (11.16%), were susceptible to the antibiotics tested in this study (p < 0.05). Monitoring susceptibility patterns of these non-resistant strains remains crucial to prevent the development of resistance.\n\nIn Figure 8A, a detailed analysis of mecA gene detection among S. aureus isolates is presented, including both count and proportion of detections. Of the total isolates analyzed, 178 (82.79%) tested positive for the mecA gene, indicating the presence of methicillin resistance mechanisms. Conversely, 37 isolates (17.21%) did not exhibit mecA gene detection, suggesting the absence of this specific genetic determinant associated with methicillin resistance. Further analysis based on methicillin resistance status reveals that mecA gene detection was prevalent among MRSA isolates, with 67.91% testing positive for the gene. This underscores the strong association between mecA gene presence and methicillin resistance. Among MRSA-negative cases, mecA gene detection was considerably lower, with only 14.88% of isolates testing positive. Interestingly, a similar proportion of MRSA-negative cases also exhibited mecA gene detection, suggesting potential discrepancies or alternative mechanisms of methicillin resistance in these isolates. Additionally, the absence of mecA gene detection was observed in 2.33% of MRSA-negative cases, indicating a small subset of isolates without mecA-associated methicillin resistance.\n\nAtl text: (A) Detailed analysis of mecA gene detection. Among the total isolates analyzed, 178 (82.79%) tested positive for the mecA gene, indicating methicillin resistance mechanisms. Conversely, 37 isolates (17.21%) were negative for the mecA gene. Analysis based on methicillin resistance status reveals that 67.91% of MRSA isolates tested positive for the mecA gene, underscoring the association between mecA presence and methicillin resistance. Among MRSA-negative cases, 14.88% were positive for the mecA gene, suggesting potential alternative resistance mechanisms. Additionally, 2.33% of MRSA-negative cases showed no mecA detection, indicating the absence of this methicillin resistance determinant in a small subset of isolates. (B) Comprehensive analysis of PVL gene detection. Among all isolates analyzed, 90 (41.86%) were positive for the PVL gene, indicating its prevalence among the sampled S. aureus strains. Conversely, 125 isolates (58.14%) were negative for the PVL gene. Examination based on methicillin resistance status shows that 35.35% of MRSA isolates had the PVL gene, while 6.51% of MRSA-negative cases were positive for the gene. Interestingly, 47.44% of non-MRSA isolates exhibited the presence of the PVL gene, indicating its occurrence in a significant proportion of methicillin-sensitive S. aureus strains. Additionally, 10.7% of non-MRSA isolates did not detect the PVL gene.\n\nIn Figure 8B, a comprehensive analysis of PVL gene detection among S. aureus isolates is provided, considering both count and proportion of detections. Among all isolates analyzed, 90 (41.86%) tested positive for the presence of the PVL gene, indicating its prevalence among the sampled S. aureus strains. Conversely, 125 isolates (58.14%) did not exhibit detection of the PVL gene. Further examination based on methicillin resistance status shows that among MRSA isolates, the detection of the PVL gene was observed in 35.35% of cases, indicating its presence in a significant proportion of methicillin-resistant strains. In contrast, among MRSA-negative cases, the detection rate of the PVL gene was notably lower, with only 6.51% of isolates testing positive. This suggests a reduced prevalence of the PVL gene among methicillin-sensitive S. aureus strains. Interestingly, a considerable percentage of non-MRSA isolates exhibited the presence of the PVL gene, with 47.44% of MRSA-negative cases testing positive for its detection. This indicates that the PVL gene is not exclusive to MRSA strains and is also present in a substantial proportion of methicillin-sensitive S. aureus strains. Additionally, 10.7% of non-MRSA isolates did not show detection of the PVL gene.\n\n\nDiscussion\n\nAl-Tawalbeh et al. (2023) proposed a novel approach in MRSA treatment by combining carvacrol - a component of essential oils, with approved antibiotics. Carvacrol has demonstrated antimicrobial activity against both gram-positive and gram-negative bacteria. The study revealed that the combination of carvacrol with antibiotics provided better efficacy compared to monotherapy, particularly showing superior results with linezolid, minocycline, and sulfamethoxazole. This suggests potential synergistic or additive effects between carvacrol and certain antibiotics. Specifically, among MRSA isolates, carvacrol combined with linezolid, minocycline, and sulfamethoxazole exhibited the following proportions of detections: 87.3%, 89.5%, and 84.2%. In the study by Rubio-Garcia et al. (2023), some antiretroviral drugs exhibited antibacterial activity against human commensal bacteria and multidrug-resistant pathogens, including MRSA. This highlights the potential repurposing of antiretroviral drugs for treating bacterial infections, particularly in cases of multidrug resistance. Notably, elvitegravir showed antibacterial activity against G. vaginalis and P. bivia, as well as against vancomycin-resistant Enterococcus spp. and MRSA strains, with MIC values ranging from 4 to 16 μg/mL. Sun et al. (2024b) emphasized the role of antibiotic misuse in the rise of multidrug-resistant organisms (MDROs) and identified factors contributing to postoperative MDRO infections. Their findings underscored the importance of judicious antibiotic use, shorter operative times, and increased patient mobility in preventing surgical-site infections with MDROs. Furthermore, among patients with limb fractures, the risk factors for MDRO infection included being bedridden (OR, 2.66; P = 0.037), repeated infection (OR, 4.00; P = 0.005), and an operative time of >3 h (OR, 2.28; P = 0.023). Kungu et al. (2024) revealed the prevalence of MRSA among humans and animals in Uganda. Their study highlighted the need for surveillance of antimicrobial resistance and promotion of rational antibiotic use to mitigate the spread of resistant strains. Among human and cattle samples, S. aureus isolates showed high levels of resistance to Nitroimidazoles (100%) and Penicillins (93.3%). Additionally, 93% of human isolates exhibited multidrug resistance (MDR). Islam (2024) evaluated the efficacy of vancomycin AUC-based dosing for non-MRSA infections. While AUC-based dosing may be necessary for MRSA cases, its impact on non-MRSA infections was less pronounced. In patients with non-MRSA infections, the overall early response rate to vancomycin AUC-based dosing was 50.3%, with a 30-day all-cause mortality rate of 11.3% and a rate of acute kidney injury (AKI) of 3.8%. Woźniak et al. (2024) demonstrated that eliminating environmental reservoirs and implementing improved infection control measures in the ICU reduced the incidence of infections caused by MDROs. This study emphasizes the importance of comprehensive infection control strategies in healthcare settings. Infections with MDR strains, particularly Klebsiella pneumoniae NDM, were observed to spread from hand-wash basins in wards and from inside air conditioners on the ceiling outside patient rooms.\n\nThe study conducted provides a comprehensive analysis of both antibiotic resistance patterns and demographic factors associated with S. aureus infections. By examining 568 clinical specimens, the study revealed a substantial prevalence of S. aureus, constituting 37.9% of the total samples. This high prevalence underscores the significance of understanding both the microbial and host-related determinants of S. aureus infections. Demographic analysis revealed an age-dependent pattern, with a notable increase in S. aureus prevalence among older age groups, particularly individuals aged 60-79. These findings suggest that age plays a crucial role in susceptibility to S. aureus infections, highlighting the importance of age-specific preventive strategies and targeted surveillance efforts. Furthermore, the study delved into the association between S. aureus infections and underlying health conditions, with diabetes mellitus emerging as a significant contributing factor. Over half of the cases were associated with diabetes mellitus, emphasizing the need for tailored infection prevention measures for individuals with specific comorbidities. Immunocompromised status was identified as another key determinant of S. aureus infections, with a substantial proportion of cases (63.26%) occurring in immunocompromised individuals. This underscores the heightened vulnerability of immunocompromised patients to S. aureus infections and emphasizes the critical role of immune function in protecting against bacterial pathogens. In addition to demographic factors, the study investigated the distribution of S. aureus infections across different hospital departments. The Internal Medicine Department (IMD) exhibited the highest count of S. aureus cases, suggesting a significant presence of S. aureus infections among patients seeking treatment in this department. This highlights the importance of targeted infection control measures in high-prevalence medical departments. Turning to antibiotic resistance patterns, the study revealed widespread resistance of S. aureus isolates to multiple classes of antibiotics, particularly beta-lactams and macrolides. The predominance of multidrug-etresistant (MDR) strains, comprising 84.19% of cases, underscores the challenges in treatment selection and the urgent need for antimicrobial stewardship programs. Moreover, the emergence of extensively drug-resistant (XDR) strains further complicates treatment options, emphasizing the pressing need for novel therapeutic approaches and surveillance strategies to combat antimicrobial resistance.\n\nIn conclusion, the integration of antibiotic resistance patterns and demographic factors provides a holistic understanding of S. aureus infections, enabling the development of targeted interventions to mitigate the spread of antimicrobial resistance and improve clinical outcomes. By addressing both microbial and host-related determinants, healthcare professionals can optimize infection control measures and treatment strategies to effectively manage S. aureus infections in diverse patient populations.\n\nS. aureus, particularly MRSA, poses a significant challenge in healthcare settings due to its ability to resist multiple antibiotics. The emergence of antibiotic resistance, especially to beta-lactam antibiotics, has complicated treatment strategies over the years (John, 2020). The mecA gene, carried within the SCCmec cassette, is a key determinant of methicillin resistance in S. aureus. It encodes penicillin-binding protein 2a (PBP2a), which alters the peptidoglycan synthesis pathway, rendering the bacteria resistant to beta-lactam antibiotics (Tasneem et al., 2022). This genetic mechanism allows MRSA strains to proliferate even in the presence of beta-lactam antibiotics, leading to prolonged hospital stays and increased mortality rates (Algammal et al., 2020). Studies have highlighted the clinical manifestations and epidemiology of MRSA infections, emphasizing the need for novel treatment strategies (Shoaib et al., 2022). While vancomycin remains a standard treatment option, the rise of resistance underscores the urgency for alternative therapies (John, 2020). Several newer agents, including trimethoprim-sulfamethoxazole, ceftaroline, daptomycin, and linezolid, have shown promising activity against resistant staphylococci (John, 2020). Understanding the molecular determinants of antibiotic resistance in MRSA, particularly the role of mecA-encoded PBP2a, is crucial for developing effective treatment approaches (Lade & Kim, 2023). Furthermore, surveillance of mecA-mediated resistance in non-aureus staphylococci and mammaliicocci highlights the importance of One Health approaches in combating antibiotic resistance (Abdullahi et al., 2023). The spread of mecA/mecC-carrying strains, particularly in mastitis cases, underscores the need for vigilant monitoring and control measures in veterinary settings (Abdullahi et al., 2023). While the mecA gene plays a central role in conferring methicillin resistance, other genetic determinants and virulence factors contribute to the complexity of MRSA infections (Akoua-Koffi et al., 2022). Understanding the interplay between these factors and their impact on antibiotic resistance is essential for devising comprehensive treatment and prevention strategies. In conclusion, the mecA gene significantly influences the antibiotic resistance profile of S. aureus, particularly MRSA. Further research into the molecular mechanisms underlying resistance and the development of targeted therapies are critical in addressing the global threat posed by antibiotic-resistant staphylococci.\n\nThe presence of the PVL gene in S. aureus strains has been associated with various clinical manifestations and disease outcomes, including skin and soft tissue infections (SSTIs), osteomyelitis, and potentially malignant transformations such as PVL. Understanding the implications of the PVL gene on antibiotic resistance in S. aureus is crucial for effective clinical management and treatment strategies. Studies by Leistner et al. (2022) and Pimentel de Araujo et al. (2021) highlight the prevalence of PVL-producing S. aureus strains in clinical settings, particularly in cases of SSTIs and osteomyelitis. Leistner et al. (2022) reported a detection rate of 61.3% for the PVL gene in skin and soft tissue infections, with PVL-positive strains showing a higher recurrence rate compared to PVL-negative strains. Furthermore, PVL-SA infections are associated with specific clinical features, including leukocytolysis and dermatonecrosis, which contribute to the severity and management of these infections. The emergence of antibiotic-resistant S. aureus strains poses significant challenges in the treatment of infections. Tromp and van Strijp (2020) discussed the role of PVL and other leukocidins as virulence factors that contribute to the pathophysiology of S. aureus infections. While the exact mechanisms remain incompletely understood, the involvement of PVL in the epidemic spread and increased virulence of community-acquired methicillin-resistant S. aureus (CA-MRSA) strains underscores the need for novel treatment approaches. Effective management of PVL-associated infections requires a multidisciplinary approach, as emphasized by Khurana et al. (2021). Early and accurate diagnosis, along with appropriate intervention, is essential for therapeutic recovery and rehabilitation, particularly in vulnerable populations such as children with periventricular leukomalacia (PVL) or patients with atopic dermatitis (AD) prone to S. aureus infection. Hulme (2023) highlighted the importance of tailored treatments targeting underlying pathological mechanisms, such as SA toxins and impaired immune responses, in AD patients with S. aureus infections. Further research is needed to elucidate the complex interplay between the PVL gene, antibiotic resistance, and clinical outcomes in S. aureus infections. Studies such as those by Wei et al. (2022) and provide insights into the association between S. aureus infections and carcinogenesis, suggesting potential implications for cancer diagnosis and treatment. Additionally, ongoing efforts to characterize the molecular epidemiology of S. aureus clones causing infections, as described by Pimentel de Araujo et al. (2021), will contribute to a better understanding of disease transmission and evolution. In conclusion, the presence of the PVL gene in S. aureus strains significantly influences clinical manifestations, treatment outcomes, and antibiotic resistance profiles. A comprehensive understanding of the impact of PVL on disease pathogenesis and progression is essential for the development of targeted therapeutic interventions and infection control strategies. Collaborative research efforts combining clinical, molecular, and epidemiological approaches will further advance our knowledge of PVL-associated infections and improve patient outcomes in clinical practice.\n\nThe findings presented in this study offer valuable insights into the prevalence and association of key genetic determinants, namely the mecA gene associated with methicillin resistance and the PVL gene, among S. aureus isolates. In Figure 8A, the detection of the mecA gene is highlighted, revealing that a significant majority (82.79%) of the analyzed isolates tested positive for this genetic determinant. This high proportion underscores the pervasive nature of methicillin resistance mechanisms among the sampled S. aureus strains. Moreover, the strong association between mecA gene presence and methicillin resistance is further emphasized by its prevalent detection among MRSA isolates (67.91%). Interestingly, the observation of mecA gene detection in a subset of MRSA-negative cases (14.88%) suggests potential alternative mechanisms of methicillin resistance or discrepancies in MRSA classification. Figure 8B focuses on the detection of the PVL gene, revealing its presence in 41.86% of all analyzed isolates. Among MRSA isolates, the PVL gene was detected in 35.35% of cases, indicating its prevalence in methicillin-resistant strains. Conversely, among MRSA-negative cases, the detection rate of the PVL gene was notably lower (6.51%), suggesting a reduced prevalence among methicillin-sensitive strains. However, the significant percentage of non-MRSA isolates exhibiting the presence of the PVL gene (47.44%) indicates that it is not exclusive to MRSA strains. This highlights the potential role of the PVL gene in a broader spectrum of S. aureus infections, irrespective of methicillin resistance status. Overall, these findings underscore the complex interplay between genetic determinants, antibiotic resistance, and virulence factors in S. aureus strains. Further research is warranted to elucidate the mechanisms underlying methicillin resistance and the role of the PVL gene in S. aureus pathogenesis, which could inform the development of targeted therapeutic interventions and infection control strategies.\n\n\nConclusion\n\nThis study provides valuable insights into the prevalence of S. aureus infections and the associated antibiotic resistance patterns, focusing on the key resistance-associated genes mecA and PVL. The high prevalence of MRSA and MSSA underscores the importance of tailored management strategies to address these distinct variants effectively. The widespread resistance observed among S. aureus isolates highlights the urgent need for judicious antibiotic use and surveillance to mitigate antimicrobial resistance. The significant association between mecA gene presence and methicillin resistance reaffirms its pivotal role in MRSA evolution and underscores the challenges in treating infections caused by these strains. Moreover, the prevalence of the PVL gene across S. aureus strains highlights its role as a virulence factor and emphasizes its contribution to disease pathogenesis and rapid dissemination.\n\nThese findings underscore the importance of comprehensive strategies encompassing surveillance, infection control measures, and the development of novel therapeutic interventions targeting key resistance and virulence factors. Collaborative efforts across healthcare sectors are crucial to combatting antimicrobial resistance and improving patient outcomes in S. aureus infections. Further research into the molecular mechanisms underlying resistance and virulence will enhance our understanding and inform the development of targeted interventions to address this pressing public health concern.\n\nEthical approval for this study was obtained from the Ethics Council in Biomedical Research at Can Tho University of Medicine and Pharmacy on May 28, 2020, under Reference Number: 421/QD-DHYD. The study involving human participants strictly adhered to the ethical principles outlined in the Declaration of Helsinki. The protocol was thoroughly reviewed and approved by the Ethics Council, ensuring that all ethical requirements were met. Written informed consent was obtained from each participant prior to their involvement in the study.",
"appendix": "Data availability\n\nTo ensure transparency and reproducibility, we have deposited all the raw data underlying this study in BioStudies. You can access the data via the following link: Be-Hai Nguyen-Thi, Ngoc-Nga Pham-Thi, Hai-Yen Nguyen-Thi, Long-Nguyen Nguyen, & Trung-Son Le (2024). Unraveling the genetic basis of antibiotic resistance in Staphylococcus aureus: Focus on mecA and PVL gene. BioStudies, S-BSST1482. Retrieved from https://www.ebi.ac.uk/biostudies/studies/S-BSST1482. DOI: 10.6019/S-BSST1482.\n\nThe project contains the following underlying data:\n\n• Staphylococcus aureus.csv\n\nData are available under the terms of the CC0 1.0 UNIVERSAL (CC0).\n\nArticles reporting observational studies followed the STROBE guidelines.\n\n\nAcknowledgement\n\nGratitude is extended to Can Tho University of Medicine and Pharmacy for their generous support of the research project, which included providing access to necessary samples and testing facilities. Sincere appreciation is also expressed to all those who contributed to the project and aided in the research endeavors.\n\n\nReferences\n\nAbdullahi IN, Latorre-Fernandez J, Reuben RC, et al.: Beyond the Wild MRSA: Genetic Features and Phylogenomic Review of mecC-Mediated Methicillin Resistance in Non-aureus Staphylococci and Mammaliicocci. Microorganisms. 2023; 12(1). PubMed Abstract | Publisher Full Text | Free Full Text\n\nAkoua-Koffi C, Kacou N’Douba A, Djaman JA, et al.: Staphylococcus schweitzeri-An Emerging One Health Pathogen? Microorganisms. 2022; 10(4). PubMed Abstract | Publisher Full Text | Free Full Text\n\nAl-Tawalbeh D, Alkhawaldeh Y, Abu Sawan H, et al.: Assessment of carvacrol-antibiotic combinations’ antimicrobial activity against methicillin-resistant Staphylococcus aureus. Front. Microbiol. 2023; 14: 1349550. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlgammal AM, Hetta HF, Elkelish A, et al.: Methicillin-Resistant Staphylococcus aureus (MRSA): One Health Perspective Approach to the Bacterium Epidemiology, Virulence Factors, Antibiotic-Resistance, and Zoonotic Impact. Infect. Drug Resist. 2020; 13: 3255–3265. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAntosz K, Battle S, Chang J, et al.: Cefazolin in the treatment of central nervous system infections: A narrative review and recommendation. Pharmacotherapy. 2023; 43(1): 85–95. PubMed Abstract | Publisher Full Text\n\nArif M, Fang G, Fida H, et al.: iMRSAPred: Improved Prediction of Anti-MRSA Peptides Using Physicochemical and Pairwise Contact-Energy Properties of Amino Acids. ACS Omega. 2024; 9(2): 2874–2883. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCassat JE, Thomsen I: Staphylococcus aureus infections in children. Curr. Opin. Infect. Dis. 2021; 34(5): 510–518. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nIslam I: Vancomycin AUC-Based Dosing Practices in a Non-Teaching Community Hospital and Associated Outcomes: A One-Year Survey of Uniform Targets for Infections with or without MRSA. Pharmacy (Basel). 2024; 12(1). PubMed Abstract | Publisher Full Text | Free Full Text\n\nJohn JJ: The treatment of resistant staphylococcal infections. F1000Res. 2020; 9: 150. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhurana R, Shyamsundar K, Taank P, et al.: Periventricular leukomalacia: an ophthalmic perspective. Med. J. Armed Forces India. 2021; 77(2): 147–153. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKungu JM, Tegule SS, Awke IA, et al.: Antimicrobial susceptibility profiles of Staphylococcus aureus in cattle and humans in farming communities of Isingiro and Kamuli districts, Uganda. Sci. Rep. 2024; 14(1): 1900. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLade H, Kim JS: Molecular Determinants of beta-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus (MRSA): An Updated Review. Antibiotics (Basel). 2023; 12(9). PubMed Abstract | Publisher Full Text | Free Full Text\n\nLe TS, Nguyen PT, Nguyen HSH, et al.: Expression of genes involved in exopolysaccharide synthesis in Lactiplantibacillus plantarum VAL6 under environmental stresses. Arch. Microbiol. 2021; 203(8): 4941–4950. PubMed Abstract | Publisher Full Text\n\nLee JH: Methicillin (Oxacillin)-resistant Staphylococcus aureus strains isolated from major food animals and their potential transmission to humans. Appl. Environ. Microbiol. 2003; 69(11): 6489–6494. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLeistner R, Hanitsch LG, Kruger R, et al.: Skin Infections Due to Panton-Valentine Leukocidin-Producing S. aureus. Dtsch. Arztebl. Int. 2022; 119(45): 775–784. 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PubMed Abstract | Publisher Full Text\n\nTran LS, Pham TNN, Truong BV, et al.: Epidemiology and antibiotic resistance assessment of Acinetobacter baumannii isolates from respiratory specimens collected at Can Tho General Hospital. J. App. Biol. Biotech. 2023; 12(1): 198–204. Publisher Full Text\n\nTromp AT, van Strijp JAG : Studying Staphylococcal Leukocidins: A Challenging Endeavor. Front. Microbiol. 2020; 11: 611. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWei Y, Sandhu E, Yang X, et al.: Bidirectional Functional Effects of Staphylococcus on Carcinogenesis. Microorganisms. 2022; 10(12). PubMed Abstract | Publisher Full Text | Free Full Text\n\nWoźniak A, Janc J, Łysenko L, et al.: How to Defeat Multidrug-Resistant Bacteria in Intensive Care Units. A Lesson from the COVID-19 Pandemic. Prevention, Reservoirs, and Implications for Clinical Practice. Int. J. Med. Sci. 2024; 21(3): 530–539. PubMed Abstract | Publisher Full Text | Free Full Text"
}
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[
{
"id": "309288",
"date": "14 Aug 2024",
"name": "Heather B. Miller",
"expertise": [
"Reviewer Expertise molecular 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\nMajor comments: These are points that would make the paper scientifically sound.\nWhile the figures are clear, the interpretations of them are not entirely appropriate. Often, the authors state that a result highlights something (age, immunocompromised status, etc), which it does. However, to conclude that the results reveal a clear understanding of an association is a stretch. For example, determining that a particular age group has a higher rate of S. aureus infections compared to others in this study highlights the important of age among this particular group of individuals in this country at this health care facility. But it does not provide a clear understanding of how age is associated with infection, given that it is limited in geography and strains not found in this setting would be found in others worldwide. Please adjust the language so as to not overstate the findings. Please include limitations of the study in its own paragraph in the Discussion section.\nThere are no clear hypotheses stated anywhere. This gives the manuscript a meandering flow, where the reader is unsure where they are going next.\nMinor comments: These are points that would strengthen the paper.\nIn the introduction, “the research aims to” reads like the research reported here is aiming to …”But these specific aims are not addressed. For example, the authors write about the epidemic spread of S. aureus, yet the manuscript describes clinical samples from one hospital. Therefore, it would be beneficial to rephrase these sentences to something like “the research in this field aims to”.\nIt is unclear why the methods section states patients had S. aureus infections, yet only 37.9% of isolates tested positive for S. aureus.\nIn Figure 2, it would be helpful to indicate the actual p value associated with the age group that had a higher rate of S. aureus present. It is currently only in the figure legend. Throughout, p values can be revealed, rather than just “less than 0.05”. Additionally, it is unclear if each pairwise group comparison resulted in p <0.05 of if only certain comparisons yielded this. Please add the customary comparison markings on the bar graphs throughout.\nAvoid the repetitive phrase “valuable insights”.\nThe flow of the results section can be strengthened by not starting so many paragraphs with “Figure 4 shows…, “Figure 5 shows….”\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? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12277",
"date": "27 Aug 2024",
"name": "Ngoc-Nga Pham-Thi",
"role": "Author Response",
"response": "Dear Dr. Miller, Thank you for your thorough review. We appreciate your insights and will address the main points as follows: Key comments: We revised figure interpretations to accurately reflect the study's scope, avoiding overgeneralization. A limitations section will be added. Clear hypotheses were stated at the beginning to improve coherence. Minor points: The introduction was reworded to clarify our specific research focus. We were explain patient selection criteria and S. aureus prevalence rate. Repetitive phrases revised and results presentation improved. We believe these changes will significantly enhance the manuscript. Thank you again for your valuable feedback. Sincerely, Pham, T.N.N"
}
]
}
] | 1
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https://f1000research.com/articles/13-802
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https://f1000research.com/articles/13-773/v1
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08 Jul 24
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{
"type": "Research Article",
"title": "Molecular docking studies and molecular dynamic simulation analysis: To identify novel ATP-competitive inhibition of Glycogen synthase kinase-3β for Alzheimer’s disease",
"authors": [
"Suggala Ramya Shri",
"Yogendra Nayak",
"Sreedhara Ranganath Pai",
"Suggala Ramya Shri",
"Yogendra Nayak"
],
"abstract": "Background The discovery of an ideal and effective therapy is urgently required for the treatment of Alzheimer’s disease. The main pathological hallmarks of Alzheimer’s disease that appear before the clinical symptoms are neurofibrillary tangles, amyloid plaques, brain inflammation, and neuronal atrophy throughout the cerebral cortex and hippocampus. GSK-3β (Glycogen Synthase Kinase-3β) is regarded as the most important and promising target for therapeutic use because GSK-3β expression levels increase with age and are the most abundant and hyperactive in the brains of patients with Alzheimer’s disease.\n\nMethods We used Maestro, which is Schrodinger, for our computational simulation studies. In the present work, we have used different modules that were used in previous studies with a little modification, the modules such as Protein Preparation with the help of Protein Preparation Wizard, Ligand Preparation with the help of LigPrep, for ADME (Absorption, Distribution, Metabolism and Excretion) prediction we used Qikprop, Docking studies we used Glide module, Binding energy prediction we used Prime and Molecular dynamic simulation studies by Desmond\n\nResults Our focus is mainly on an in-silico approach, focusing on library generation; we first drew an imidazo [1,5-a]pyridine-3-carboxamide (IMID 2) scaffold structure at Enamine and subjected it to a substructure search to target the receptor grid region (ATP-competitive site) of 6Y9R. They were then subjected to various screening processes. Finally, we selected nine compounds and subjected them to molecular dynamic simulation studies.\n\nConclusions Nine compounds showed good results with the most stable interactions. Further experiments and studies are required to confirm these results.",
"keywords": [
"Alzheimer’s disease",
"GSK-3β",
"ATP-competitive study",
"Protein preparation",
"Ligand Preparation",
"Qikprop",
"Glide module",
"Prime MM-GBSA",
"Molecular dynamic simulation."
],
"content": "Introduction\n\nOne of the greatest threats to public health is neurodegenerative diseases because there is no exact therapy. Therefore, the discovery of an ideal and effective therapy is urgently needed for the treatment of Alzheimer’s disease.1 Only five to seven cases are due to genetic mutations, and the remaining cases are due to environmental factors and sporadic mutations. The main pathological hallmarks of Alzheimer’s disease that appear before the clinical symptoms are neurofibrillary tangles, amyloid plaques, brain inflammation, and neuronal atrophy throughout the cerebral cortex and hippocampus.2 Memory loss can be elicited in Alzheimer’s patients, such as episodic short-term memory impairment followed by a lack of motivation, disorganization, and impairment in solving problems, judgment, and executive functioning. In early stage impairments, such as visuospatial skills, neuropsychiatric symptoms are most common in mild and late-stage Alzheimer’s disease.3 The heritability of AD is estimated to be between 60% and 80%, and these components allow for the identification and determination of pathophysiological processes, diagnostic markers, biological targets, and new treatment targets through genomics translational studies.4 Glycogen synthase kinase-3 (GSK-3) is a member of the protein kinase family and is widely expressed in tissues. GSK-3 is a Serine/Threonine kinase that transfers a phosphate group to either the serine or threonine residue of its substrate target.5 GSK-3β is regarded as the most important and promising therapeutic target. The etiology and pathogenesis of AD are not completely understood. However, available treatments have failed to show novel approaches and effectiveness, and the efficacy of drugs varies from one person to another.6 GSK-3β expression levels increase with age and are most abundant and hyperactive in the brains of patients with AD. Hence, dysregulation of GSK-3β automatically affects amyloid beta plaques, which have been previously shown in in vitro and in vivo Alzheimer’s disease models.7 GSK-3 plays a very important key role in the metabolic process and regulating structural processes in adult neurons as well as in developing neurons.8 In the present study, we used a molecular modeling approach.\n\n\nMethods\n\nWe used Maestro for our computational simulation studies; the graphical interface was Schrödinger. In the present work, we used different modules that were used in previous studies with slight modifications: Protein Preparation Wizard, Ligand Preparation with the help of LigPrep, for ADME (Absorption, Distribution, Metabolism and Excretion) prediction, we used Qikprop, Docking studies we used the Glide module, and binding energy prediction we used Prime and Molecular dynamic simulation studies by Desmond.9–11 Alternatively freely available software are AutoDock 4, ArgusLab, and Gromacs,\n\nWe used PDB I.D: 6Y9R (http://www.rcsb.org/)12 of GSK-3β, which is bound to a co-crystallized ligand with a Resolution of 2.08 Å consisting of only chain A, downloaded from the protein databank site,10,11 and imported this PDB I. D to the Maestro interface. This is followed by preparing the protein molecule with the help of the protein preparation wizard panel of the Schrödinger suite. Alternatively, the AutoDock 4 which is freely available software can be used. The first step for protein preparation is preprocessing in the workspace the protein structure is selected then Assigned bond orders, using the CCD database, explicit hydrogen to the structure, zero-order bonds to metals, creating disulfide bonds, and optimizing missing side chain atoms by running a Prime job, fill in missing loops by running the Prime job was selected and delete waters that are further than specified distance beyond 5.00 Å from any of the het groups including ions. This is recommended for Glide and virtual screening, but Molecular Dynamics applications should keep these water as they will help the equilibrate the solvent box faster and generate het states using Epik pH: 7.5±0.0, and clicked for preprocessing. The second step is to review and modify here when a new chain, water, or het is selected to zoom to fit the selection to the workspace, select waters and hets within 5.0 Å of selected chains, and keep the remaining residues and chains as the default setting and generate a state pH of 7.5±0.0. The third step is to refine we have selected sample water orientations in addition to other groups, and the protonation states of residues and ligands were set by using PROPKA pH: 7.5 then it simulated the exact experimental conditions and clicked to automatically optimize hydroxyl, Asn, Gln, His states using ProtAssign, removing water that is further than beyond hets 3.0 Å, including ions. This is recommended for Glide and virtual screening, but Molecular Dynamics applications should keep this water as it will help equilibrate the solvent box faster. We used the OPLS3e force field for the restrained minimization of proteins. After minimization, the glycerol and acetate ions were removed from the minimized protein.\n\nImidazo [1,5-a]pyridine-3-carboxamide (IMID 2) scaffolds were used for this study. This scaffold possesses fewer hydrogen bond donors and improved Central Nervous System (CNS) penetration at micromolar concentrations (μM), based on studies by Buonfiglio et al.13 To generate the focus library, we first drew an imidazo[1,5-a]pyridine-3-carboxamide (IMID 2) scaffold structure at Enamine and subjected it to a substructure search. Then, we obtained enamine realdb_IMID2_Scaffold_molecules (1400 molecules), followed by ligand preparation using LigPrep in the Schrödinger suite software (Schrödinger 2021-3).14 Alternatively, the AutoDock 4 which is freely available software can be used. The 3D coordinates for the compounds were generated using the LigPrep tool, and the Epik module predicted the most probable charge form for the ionization state of compounds at pH: 7.5±0.0, generated tautomers and stereoisomers, determined chiralities from the 3D structure, generated at most 32 per ligand, and finally, the minimization of the drug molecule process was performed using the force field OPLS3e.15,16\n\nAfter ligand preparation, all ligands were subjected to Qikprop in the Schrödinger suite software to predict the ADME profile of the compounds. QikProp predicts the drug-like properties of all selected compounds, such as molecular weight, Hydrogen Bond Donors, Hydrogen Bond Acceptor, QPlogS (predicted aqueous solubility), QPlogPo/w (predicted octanol/water partition coefficient), QPlogBB (predicted brain/blood partition coefficient), QPlogPw (predicted water/gas partition coefficient), QPlogPC16 (predicted hexadecane/gas partition coefficient), QPlogPoct (predicted octanol/gas partition coefficient), PSA (Van der Waals surface area of polar nitrogen and oxygen atoms), QPPCaco (predicted apparent Caco-2 cell permeability), and QPPMDCK (predicted apparent MDCK cell permeability).17\n\nHere, we used the Schrödinger suite Glide module to better understand the prediction of the protein-ligand involved in assessing the fitting of all conformations of compounds at the binding site followed by ranking and modes Schrödinger Release 2021-3. The alternative freely accessible softwares are AutoDock and Gromacs. The molecular docking study process was used for assessment before molecular docking studies, and the default settings were used for the Receptor Grid generation module. The binding site was recognized using the Receptor Grid generation module, and this binding site was specified as a box of 10 × 10 × 10 Å3 centered on the centroid of the co-crystallized ligand of GSK-3β, which was taken into consideration for grid generation.18 We subjected all prepared compounds to the standard precision (SP) scoring function mode.19 Glide SP docking ligand sampling is in flexible mode and selected sample nitrogen inversions, sample ring conformations, and amides only penalize non-planar conformations, adding Epik state penalties to the docking score. In the output file, we selected the pose viewer file that includes the receptor, written out at most one pose per ligand, performed post-docking minimization, the number of poses per ligand to include was five, and the RMSD was computed to input ligand geometries and run the job. Finally, the results were analyzed, separated, and selected based on the VAL135 residue interaction and physicochemical properties reported in the literature. These compounds were then subjected to the prime-MMGBSA module.\n\nMM-GBSA (molecular mechanics-generalized born energies & surface area/accessibility continuum solvation method) was used to calculate the binding free energy and binding analysis of 523 SP docked protein-ligand complexes. MM-GBSA exhibits many energy properties for proteins, ligands, and complex structures. Prime MM-GBSA analysis is based on the solvent model of VSGB 2.0, and the OPLS3e force field is used to calculate the binding affinity of the respective protein-ligand complex.20\n\nThis model was used to precisely predict the interaction of the ligand with 6Y9R (protein), the stability of their binding under physiological conditions, and to analyze their motion at the molecular and atomic levels. The protein-ligand complex was subjected to a system built here, and different solvent models were selected; an orthorhombic box with dimensions of 10 Å × 10 Å × 10 Å was used to determine the structure geometry to have the minimum box volume, and the checked boundary box is shown in the workspace. The next step is to load the previous system builder file and enter 100ns in simulation time, 1000frames were captured, ensemble class is NPT (Normal Pressure Temperature), 300°K temperature, pressure bar is 1, and relax model system before simulation was used for molecular dynamic simulation studies.21 After Molecular dynamic simulation, the analysis was done with the help of the RMSD (Root Mean Square Deviation), the RMSD of ligand, RMSD of protein. RMSD is mainly used to determine the stability of the protein-ligand complex, RMSF (Root Mean Square Fluctuations), ligand-protein contacts, and ligand interaction diagram. Alternatively, NAMD molecular simulation along with VMD software can be used which is freely available.\n\n\nResults and Discussion\n\nWhen we searched for PDB in UniProt, we identified 89 GSK-3β human PDBs. out of 89 PDB entries, 8 PDB literature are yet to be published, and some PDBs with position 3-12 amino acids residual chains C and D are removed from my PDB selection list. PDBs that have chain A/B are taken into consideration, and we studied all the PDBs individually. Finally, we decided on PDB: 6Y9R.25\n\nThe co-crystal structure of 2 was in complex with PDB I. D 6Y9R, which is a GSK-3β enzyme. While INDZ was located at the hinge region, the piperidine chain was exposed to the solvent towards ARG141, Pyridine formed a hydrogen bond with LYS85, nearer to the ligand several hydration sites with residues such as THR138, ASN186, GLN185, LEU132, ASP200, and IIE62 were found to be fully explained in a previous study. The INDZ core scaffold was located in the ATP-competitive binding site of GSK-3β between the N-terminal lobe and the C-terminal lobe region of the protein, and INDZ was previously developed as a novel GSK-3β inhibitor using computational tools. The N-2 of the core and VAL135 N-H group, hydrogen at position N-1 of the core with the ASP133 carbonyl group, hydrogen of the carboxamide group, and VAL135 carbonyl group are important interactions. The R1 substituent appended to the core is oriented towards ARG141 in the external solvent-accessible part of the solvent, and the R2 substituent appended to the LYS85 inner cavity proximity. The indazole N-Ha was then replaced with the C-Ha group, and the ring nitrogen atoms were shuffled, resulting in the IMID2 core.13\n\nThe docked ligands accommodated in the ATP-binding site are similar to the co-crystal structure of the 6Y9R protein. The overlap of the co-crystal structures of the 6Y9R and IMID2 substructures is shown in Figure 1 (Figure 1A to 1I).\n\nThe docking of ligands to a particular receptor grid generated a region of the protein 6Y9R. In this study, SP docking was used. After docking, the compounds were separated and selected based on the VAL135 residue interaction in the literature. Therefore, based on the VAL135 N-H group {the H group of the VAL135 protein should show direct interaction with the nitrogen group of the ligand}. Through this process, we finalized 523 molecules of the IMID2 scaffold. Compounds with good SP-scores are listed in Table 1.\n\nThe Absorption, Distribution, Metabolism, and Excretion (ADME) or drug-likeness parameters are the most important and helpful parameters for screening compounds after SP docking studies during the drug discovery process.22 Generally, for CNS drugs, the physicochemical properties range from molecular weight 100 Da to 450 Da, hydrogen bond acceptors range from 0 to 5, hydrogen bond donor values range from 0 to 3, and the topological polar surface area value is ≤76 Å2.23 The results of this study are listed in Table 2. Whereas the previous ADME properties of 13 trial compounds with an IMID2 core scaffold molecular weight of 393.48, the hydrogen bond donor was 1. In the14 trial compound of the IMID2 core scaffold, the molecular weight was 451.56, and the hydrogen bond donors were 1. In the 15 trial compounds of the IMID2 core scaffold, the molecular weight was 336.39, and the hydrogen bond donors were 1. In 16 trials of the IMID2 core scaffold, the molecular weight was 394.47, and the number of hydrogen bond donors was 1.13\n\nCompounds were selected based on the screening process described above. Only short-listed compounds were subjected to desmonds for molecular dynamic simulations. These studies provide information related to the stability and flexibility of the molecular docking complexes. We performed this study using the MM-GBSA. This study provides information related to protein-ligand interactions, RMSD variation can be assessed, and RMSF fluctuations can be assessed for protein-ligand complexes. The complex was regarded as stable if it fell within the 3 Å range. These are the compounds\n\nIMID2 PV-002589535286: During MD simulations, the ligand-protein complex showed hydrogen-bonded interactions. The protein backbone and ligand structure exhibited higher RMSD fluctuations over the first 0-20nsec. The protein backbone and ligand fluctuations stayed within the range of 0.6 Å and 1.3 Å over the last 80nsec. The amino acid residue VAL135 formed a 95% direct hydrogen bonding interaction with the amide carbonyl, the amino acid residue VAL135 formed 42% direct hydrogen bonding interaction with imidazole in the ring structure, the amino acid residue TYR134 had 33% direct hydrogen bonding interaction, and ARG141 had a 72% PI-cation interaction with 1H-imidazole. The amide carbonyl was exposed to an H2O molecule through which it interacted with residue ILE62 (49%), as shown in Figure 2; however, it was reported in 13 triads (previous literature) that the amide carbonyl was exposed to water-mediated contacts with residues such as ILE62 and GLN185 for the IMID2 core scaffold. The 16-triad isopropoxyl group confirmed the probable water molecule interaction with the residue ASP200. The 17 triads showed an indirect interaction between the ortho substituent and residue ASN186. In the 18 triad, the di-F phenyl group was orientated towards LYS85, thus promoting an electrostatic interaction. However, VAL135 interaction formed direct hydrogen bonding interactions with amide carbonyl in all 13, 16, 17, and 18 trial compounds of previous IMID2 scaffolds.13\n\nInteraction diagram of 6Y9R with IMID2 compound code PV-002589535286 was observed during RMSD, Ligand interaction with amino acid residues of Protein Contact during Molecular dynamics simulation, protein–ligand contacts (cont.) (On the x-axis trajectory frame, the number is present, and amino acid residues are seen on the y-axis. The amino acid residues were in greater contact with ligands in the trajectory frame that appeared as a dark color shade). The VAL135 interaction fraction approached 1.4, whereas the ASP133 interaction fraction was missing in comparison to the core IMID2 scaffold from the previous literature. Protein root mean square fluctuation (RMSF) is mostly helpful for predicting changes that occur locally along the enzyme chain. These peaks provide information on how much the protein fluctuated during the molecular dynamic simulation study.\n\nIMID2 compound code Z3603284828: During the MD simulations, the ligand-protein complex exhibited hydrogen-bonded interactions. The protein backbone and ligand structure exhibited higher RMSD fluctuations during the first 20 ns. The protein backbone and ligand fluctuations stayed within the range of 0.3 Å and 0.6 Å over the last 70 nsec shown in Figure 3. The amino acid residue VAL135 formed 93% direct hydrogen bonding interaction with the amide carbonyl, the amino acid residue VAL135 formed 55% direct hydrogen bonding interaction with imidazole, and the amino acid residue ILE62 formed 35% water-mediated direct hydrogen bonding interaction with 1-hydroxycyclopropyl.\n\nInteraction diagram of 6Y9R with IMID2 compound code Z3603284828 observed during RMSD, Ligand interaction with amino acid residues of Protein Contact during Molecular dynamics simulation, protein–ligand contacts (cont.) (On the x-axis, a trajectory frame with a number is present, and amino acid residues are seen on the y-axis. The amino acid residues that were in greater contact with ligands in the trajectory frame appeared as a dark color shade). The VAL135 interaction fraction approached 1.4, whereas the ASP133 interaction fraction was missing in comparison to the core IMID2 scaffold from previous literature, and protein RMSF is mostly helpful for predicting the changes that occur locally along the enzyme chain. These peaks provide information on how much the protein fluctuated during the molecular dynamic simulation study.\n\nIMID2 compound code Z3136169169: During the MD simulations, the ligand-protein complex exhibited hydrogen-bonded interactions. The protein backbone and ligand structure exhibited higher RMSD fluctuations during the first 20 ns. The protein backbone and ligand fluctuations stayed within the range of 0.8 Å and 0.3 Å over the last 70 nsec shown in Figure 4. The amide carbonyl is exposed to hydrogen bonding and interacts with residue VAL135, and the amino acid residue VAL135 forms 76% direct hydrogen bonding interactions with imidazole.\n\nInteraction diagram of 6Y9R with IMID2 compound code Z3136169169 observed during RMSD, Ligand interaction with amino acid residues of Protein Contact during Molecular dynamics simulation, protein–ligand contacts (cont.) (On the x-axis trajectory frame, the number is present, and amino acid residues are seen on the y-axis. The amino acid residues that were in greater contact with ligands in the trajectory frame appeared as a dark color shade). The VAL135 interaction fraction approached 1.6, whereas the ASP133 interaction fraction was missing in comparison to the core IMID2 scaffold from previous literature and protein RMSF is mostly helpful for predicting the changes that occur locally along with the enzyme chain. These peaks provide information on how much the protein fluctuated during the molecular dynamic simulation study.\n\nIMID2 compound code Z2497631540: During the MD simulations, the ligand-protein complex exhibited hydrogen-bonded interactions. The protein Cα and ligand structures exhibited higher RMSD fluctuations over the first 20 ns. The protein backbone and ligand fluctuations stayed within the range of 0.4 Å and 3.7 Å over the last 70 nsec shown in Figure 5. The amino acid residue VAL135 formed 84% direct hydrogen bonding interactions with the amide carbonyl, and the amino acid residue VAL135 formed 39% direct hydrogen bonding interactions with imidazole in the ring structure.\n\nInteraction diagram of 6Y9R with IMID2 compound code Z2497631540 observed during RMSD, Ligand interaction with amino acid residues of Protein Contact during Molecular dynamics simulation, protein–ligand contacts (cont.) (On the x-axis, a trajectory frame with a number is present, and amino acid residues are seen on the y-axis. The amino acid residues that were in greater contact with ligands in the trajectory frame appeared as a dark color shade). The VAL135 interaction fraction approached 1.2, whereas the ASP133 interaction fraction was missing in comparison to the core IMID2 scaffold from previous literature, and protein RMSF is mostly helpful for predicting the changes that occur locally along the enzyme chain. These peaks provide information on how much the protein fluctuated during the molecular dynamic simulation study.\n\nIMID2 compound code Z4468779454: During the MD simulations, the ligand-protein complex exhibited hydrogen-bonded interactions. The protein Cα and ligand structures exhibited higher RMSD fluctuations over the first 20 ns. The protein backbone and ligand fluctuations stayed within the range of 0.5 Å and 0.4 Å over the last 70 nsec shown in Figure 6. The amino acid residue VAL135 formed a 96% direct hydrogen bonding interaction with the amide carbonyl, the amino acid residue VAL135 formed a 77% direct hydrogen bonding interaction with imidazole, and the amide carbonyl was exposed to the H2O molecule through which it interacted with residue ILE62, with 43% and 61% interaction with 1-hydroxypentan-2-yl.\n\nInteraction diagram of 6Y9R with IMID2 compound code Z4468779454 observed during RMSD, Ligand interaction with amino acid residues of Protein Contact during Molecular dynamics simulation, protein–ligand contacts (cont.) (On the x-axis trajectory frame, the number is present, and amino acid residues are seen on the y-axis. The amino acid residues were in greater contact with ligands in the trajectory frame that appeared as a dark color shade). The VAL135 interaction fraction approached 1.75, whereas the ASP133 interaction fraction was missing in comparison to the core IMID2 scaffold from previous literature, and protein RMSF is mostly helpful for predicting the changes that occur locally along the enzyme chain. These peaks provide information on how much the protein fluctuated during the molecular dynamic simulation study.\n\nIMID2 compound code Z2708235883: During the MD simulations, the ligand-protein complex exhibited hydrogen-bonded interactions. The protein backbone and ligand structure exhibited higher RMSD fluctuations during the first 20 ns. The protein Cα and ligand fluctuations stayed within the range of 0.5 Å and 0.2 Å over the last 70 nsec. The amino acid residue VAL135 formed 93% direct hydrogen bonding interactions with the amide carbonyl, and the amino acid residue VAL135 formed 53% direct hydrogen bonding interactions with imidazole in the ring structure, as shown in Figure 7.\n\nInteraction diagram of 6Y9R with IMID2 compound code Z2708235883 observed during RMSD, Ligand interaction with amino acid residues of Protein Contact during Molecular dynamics simulation, protein–ligand contacts (cont.) (On the x-axis trajectory frame, the number is present, and amino acid residues are seen on the y-axis. The amino acid residues that have been in more contact with ligands in the trajectory frame appear to have a dark color shade). The VAL135 interaction fraction approached 1.4, whereas the ASP133 interaction fraction was missing in comparison to the core IMID2 scaffold from previous literature, and protein RMSF is mostly helpful for predicting the changes that occur locally along the enzyme chain. These peaks provide information on how much the protein fluctuated during the molecular dynamic simulation study.\n\nIMID2_compound code Z3336252116: During MD simulations, the ligand-protein complex showed hydrogen-bonded interactions. The protein backbone and ligand structure exhibited higher RMSD fluctuations over the first 0-20nsec. The protein backbone and ligand fluctuations stayed within the range of 0.6 Å and 2.2 Å over the last 80nsec. The amino acid residue VAL135 formed 93% direct hydrogen bonding interactions with the amide carbonyl, and the amino acid residue VAL135 formed 48% direct hydrogen bonding interactions with imidazole in the ring structure, which was exposed to the H2O molecule through which it interacted with residue ILE62 (43%), as shown in Figure 8.\n\nInteraction diagram of 6Y9R with IMID2_compound code Z3336252116 observed during RMSD, Ligand interaction with amino acid residues of Protein Contact during Molecular dynamics simulation, protein–ligand contacts (cont.) (On the x-axis trajectory frame, the number is present, and amino acid residues are seen on the y-axis. The amino acid residues that have been in more contact with ligands in the trajectory frame appear to have a dark color shade). The VAL135 interaction fraction approached 1.5, whereas the ASP133 interaction fraction was missing in comparison to the core IMID2 scaffold from the previous literature. Protein RMSF is mostly helpful for predicting changes that occur locally along the enzyme chain. These peaks provide information on how much the protein fluctuated during the molecular dynamic simulation study.\n\nIMID2 compound code Z3136198649: During MD simulations, the ligand-protein complex showed hydrogen-bonded interactions. The protein backbone and ligand structure exhibited higher RMSD fluctuations over the first 0-20nsec. The protein backbone and ligand fluctuations stayed within the range of 0.7 Å and 0.5 Å over the last 80nsec. The amino acid residue VAL135 formed 83% direct hydrogen bonding interaction with amide carbonyl, and the amino acid residue VAL135 formed 49% direct hydrogen bonding interaction with imidazole in the ring structure given in Figure 9.\n\nInteraction diagram of 6Y9R with IMID2 compound code Z3136198649 observed during RMSD, Ligand interaction with amino acid residues of Protein Contact during Molecular dynamics simulation, protein–ligand contacts (cont.) (On the x-axis trajectory frame, the number is present, and amino acid residues are seen on the y-axis. The amino acid residues that have been in more contact with ligands in the trajectory frame appear to have a dark color shade). The VAL135 interaction fraction approached 1.4, whereas the ASP133 interaction fraction was missing in comparison to the core IMID2 scaffold from the previous literature. Protein RMSF is mostly helpful for predicting changes that occur locally along the enzyme chain. These peaks provide information on how much the protein fluctuated during the molecular dynamic simulation study.\n\nIMID2 compound code PV-005996498401: During MD simulations, the ligand-protein complex showed hydrogen-bonded interactions. The protein backbone and ligand structure exhibited higher RMSD fluctuations over the first 0-20nsec. The protein backbone and ligand fluctuations stayed within the range of 1.0 Å and 0.6 Å over the last 80nsec. The amino acid residue VAL135 formed 90% direct hydrogen bonding interactions with the amide carbonyl, and the amino acid residue VAL135 formed 47% direct hydrogen bonding interactions with imidazole in the ring structure, as shown in Figure 10.\n\nInteraction diagram of 6Y9R withIMID2 compound code PV-005996498401 observed during RMSD, Ligand interaction with amino acid residues of Protein Contact during Molecular dynamics simulation, protein–ligand contacts (cont.) (On the x-axis trajectory frame, the number is present, and amino acid residues are seen on the y-axis. The amino acid residues that have been in more contact with ligands in the trajectory frame appear to have a dark color shade). The VAL135 interaction fraction approached 1.85, whereas the ASP133 interaction fraction was missing in comparison to the core IMID2 scaffold from the previous literature. Protein RMSF is mostly helpful for predicting changes that occur locally along the enzyme chain. These peaks provide information on how much the protein fluctuated during the molecular dynamic simulation study.\n\n\nConclusion\n\nIn this study, we used focused library generation to target the receptor grid region (ATP-competitive site) of 6Y9R. After docking, the compounds were separated and selected based on the VAL135 residue interaction. Further prediction was performed using Qikprop and Prime MM-GBSA assays and Molecular dynamic simulation studies. Further experimental studies are required to confirm these findings.\n\nEthics and written consent were not applicable.",
"appendix": "Data availability\n\nFigshare: Molecular docking studies and molecular dynamic simulation to identify GSK-3β inhibitors for Alzheimer’s disease, https://doi.org/10.6084/m9.figshare.24592716.v1. 24\n\nThe underlying data for this project are:\n\n➢ Enamine_IMID2_Scaffold.csv\n\n➢ Enamine_IMID2_Scaffold_with nitrogen_realdb_molecules 17_35_52.sdf\n\n➢ Ligprep_enamine_IMID2_Scaffold_withnitrogen_realdb_out.csv\n\n➢ Ligprep_enamine_IMID2_SCAFFOLD_WITHNITROGEN_REALDB-out.mae\n\n➢ Prime_mmgbsa_3_out.csv\n\n➢ prime_mmgbsa_3-out.maegz\n\n➢ Prime_mmgbsa_VAL135_INTERACTION_IMID2_ENAMINE_WITHNITROGEN-out.csv\n\n➢ prime_mmgbsa_VAL135_INTERACTION_IMID2_ENAMINE_WITHNITROGEN-out.maegz\n\n➢ QIKPROP_LIGPRE_IMID2_ENAMINE_WITHNITROGEN-out.csv\n\n➢ QIKPROP_LIGPREP_ENAMINE_IMID2_SCAFFOLD_WITHNITROGEN_REALDB-out.mae\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nProtein Data Bank: 6Y9R, https://doi.org/10.2210/pdb6Y9R/pdb. 25\n\n\nAcknowledgements\n\nThe authors would like to thank the Indian Council of Medical Research (ICMR), New Delhi, India, for the ICMR-SRF (#2021-11506_F1) to Suggala Ramya Shri.\n\n\nReferences\n\nRippin I, Eldar-Finkelman H: Novel Modality of GSK-3 Inhibition For Treating Neurodegeneration. J Neurol Neuromedicine. 2018; 3(6): 5–7. Publisher Full Text\n\nSheppard O, Coleman M: Enfermedad de Alzheimer: etiología, neuropatología y patogenia. Enferm Alzheimer Descub fármacos. 2020; 1–22.\n\nMorris JC, McDade EM: Alzheimer Disease. Contin Lifelong Learn Neurol. 2022; 28(3): 648–675. Publisher Full Text\n\nBellenguez C, Küçükali F, Jansen IE, et al.: New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat. Genet. 2022; 54(4): 412–436. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPandey MK, DeGrado TR: Glycogen synthase kinase-3 (GSK-3)-targeted therapy and imaging. Vol. 6, Theranostics. Ivyspring International Publisher; 2016 [cited 2021 Apr 14]; pp. 571–593. Free Full Text\n\nShri SR, Manandhar S, Nayak Y, et al.: Role of GSK-3β Inhibitors: New Promises and Opportunities for Alzheimer’s Disease. Adv Pharm Bull. 2023; 13: 688–700. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLauretti E, Dincer O, Praticò D: Glycogen synthase kinase-3 signaling in Alzheimer’s disease. Biochim Biophys Acta Mol Cell Res. 2020; 1867(5): 118664. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRippin I, Eldar-Finkelman H: Mechanisms and therapeutic implications of gsk-3 in treating neurodegeneration. Cells. 2021; 10(2): 1–22. Publisher Full Text\n\nBaby K, Maity S, Mehta CH, et al.: Computational drug repurposing of Akt - 1 allosteric inhibitors for non - small cell lung cancer. Sci. Rep. 2023; 13: 1–25. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaby K, Maity S, Mehta CH, et al.: Targeting SARS-CoV-2 RNA-dependent RNA polymerase: An in silico drug repurposing for COVID-19. F1000Res. 2020; 9(September): 1166. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPriya K, Manandhar S, Sankhe R, et al.: Structure Based Virtual Docking and Molecular Dynamics Guided Identification of Potential Phytoconstituents from Traditionally Used Female Antifertility Plant. Tabriz Univ Med Sci. 2022; 28(2): 285–294. Publisher Full Text\n\nAltunkaya A, Bi C, Bradley AR, et al.: OUP accepted manuscript. Nucleic Acids Res. 2016; 45(October 2016): 271–281.\n\nBuonfiglio R, Prati F, Bischetti M, et al.: Discovery of novel imidazopyridine GSK-3β inhibitors supported by computational approaches. Molecules. 2020; 25(9). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMadhavi Sastry G, Adzhigirey M, Day T, et al.: Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des. 2013; 27(3): 221–234. PubMed Abstract | Publisher Full Text\n\nRoos K, Wu C, Damm W, et al.: OPLS3e: Extending Force Field Coverage for Drug-Like Small Molecules. J Chem Theory Comput. 2019; 15(3): 1863–1874. PubMed Abstract | Publisher Full Text\n\nChen IJ, Foloppe N: Drug-like bioactive structures and conformational coverage with the ligprep/confgen suite: Comparison to programs MOE and catalyst. J Chem Inf Model. 2010; 50(5): 822–839. PubMed Abstract | Publisher Full Text\n\nManual U: Schrödinger. Schrödinger.1987.\n\nKumar A, Rathi E, Kini SG: E-pharmacophore modelling, virtual screening, molecular dynamics simulations and in-silico ADME analysis for identification of potential E6 inhibitors against cervical cancer. J Mol Struct. 2019; 1189: 299–306. Publisher Full Text\n\nKumar A, Rathi E, Kini SG: Drug repurposing approach for the identification and designing of potential E6 inhibitors against cervical cancer: an in silico investigation. Struct Chem. 2020; 31(1): 141–153. Publisher Full Text\n\nLi J, Abel R, Zhu K, et al.: The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling. Proteins Struct Funct Bioinforma. 2011; 79(10): 2794–2812. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBowers KJ, Chow E, Xu H, et al.: Scalable algorithms for molecular dynamics simulations on commodity clusters. Proc 2006 ACM/IEEE Conf Supercomput SC’06. 2006;(November).\n\nAttique SA, Hassan M, Usman M, et al.: A molecular docking approach to evaluate the pharmacological properties of natural and synthetic treatment candidates for use against hypertension. Int J Environ Res Public Health. 2019; 16(6): 1–17.\n\nKharkar PS: Drugs acting on central nervous system (CNS) targets as leads for non-CNS targets. F1000Res. 2014; 3: 1–7. Publisher Full Text\n\nShri SR, Nayak Y, Pai KSR: Molecular docking studies and molecular dynamic simulation to identify GSK-3β inhibitors for Alzheimer’s disease. Dataset. figshare. 2023. Publisher Full Text\n\nKrapp S, Griessner A, Blaesse M, et al.: Crystal structure of GSK-3b in complex with the 1H-indazole-3-carboxamide inhibitor 2. Protein Data Bank. 2020. Publisher Full Text"
}
|
[
{
"id": "302509",
"date": "29 Jul 2024",
"name": "Qingchun Zhao",
"expertise": [
"Reviewer Expertise Alzheimer's Disease",
"Cancer",
"Natural Pharmaceutical Chemistry",
"Pharmaceutical chemistry"
],
"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 used computer simulation technology to select 9 compounds with GSK3 as the target, and then studied ADME prediction and molecular docking through different modules. Keep reading the paper, three questions are raised. 1. In the abstract, the author describes the method as \"we have used different modules that were used in previous studies with a little modification\", but in fact, the method used by the author is a routine application, and there is no prominent modification. 2. In the introduction section, is there only one sentence to summarize the article? 3.The content of the whole study is simple, the innovation is poor, and the workload is less, which is not enough to support a research article. Therefore, it is hoped that the author can modify some contents of the article and add some follow-up experiments to make the article more comprehensive.\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? Partly",
"responses": [
{
"c_id": "12214",
"date": "27 Aug 2024",
"name": "Sreedhara Ranganath Pai",
"role": "Author Response",
"response": "Reviewer Comment 1: In the abstract, the author describes the method as \"we have used different modules that were used in previous studies with a little modification\", but in fact, the method used by the author is a routine application, and there is no prominent modification. Response to comment 1: We used Maestro, a graphical interface of Schrodinger, for our computational simulation studies. In the present work, we have used different modules such as Protein Preparation Wizard for Protein Preparation, LigPrep for Ligand Preparation, Qikprop for ADME (Absorption, Distribution, Metabolism and Excretion) prediction, Glide for docking studies, Prime for Binding energy prediction and Desmond for Molecular dynamic simulation studies used. Reviewer Comment 2: In the introduction section, is there only one sentence to summarize the article? Response to comment 2: For better BBB permeation, the structure was finalized based on a wet lab. So, based on this literature search, we have selected core imidazole scaffold for our study, and from that core imidazole scaffold, we have drawn sub-structures in the enamine database. Then docking studies were done on the compounds and subjected to ADME (Qikprop). A molecular dynamic simulation study was conducted on nine compounds. Reviewer Comment 3: The content of the whole study is simple, the innovation is poor, and the workload is less, which is not enough to support a research article. Therefore, it is hoped that the author can modify some contents of the article and add some follow-up experiments to make the article more comprehensive. Response to comment 3: The reviewer's comment is completely one-sided. We regret to answer this comment, and we completely disagree with the reviewer's suggestion, as this work took 18 months from the conceptualization of the idea. This work is computational modelling, and our objectives are clear, and in our view, the data generated is sufficient to make the conclusion."
}
]
},
{
"id": "302510",
"date": "13 Sep 2024",
"name": "Jigna Samir Shah",
"expertise": [
"Reviewer Expertise Neurodegenerative diseases",
"oral cancer",
"breast 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\n1. Abstract can be modified. Also, in conclusion no specific compound was identified. 2. Role of GSK-3β in pathogenesis of AD can be explored more. Mechanism of GSK-3β in AD can be defined briefly in introduction section. 3. Why this PDB ID 6Y9R was selected from 89 IDs as mentioned in results and discussion. It can be elaborated briefly. Also, besides this domain, GSK-3β inhibition might be possible through different binding sites. If possible, it can also be explored. 4. There are grammatical errors and improper sentence formations in manuscript, which can be modified. Also, instead of using “we”, the authors can used indirect speech. 5. Full forms mentioned are not consistent. Mention the full form in first use and thereafter abbreviations can be used. 6. In result sections, “Protein root mean square fluctuation (RMSF) is mostly helpful for predicting changes that occur locally along the enzyme chain.” is repeatedly mentioned in each result. The authors can mention the significance of findings like RMSD, RMSF at the start in a separate paragraph, or only once in initial results. Thereafter it can be understood. 7. In ADME studies, it is mentioned that QPlogBB (predicted brain/blood partition coefficient), was predicted however, in results it is not mentioned. It can be mentioned, to evaluate blood brain barrier permeability. In AD, since the target region for therapy is brain, BBB permeability is a significant parameter. 8. No standard drug or inhibitor is included in MDS studies. If possible, a standard can be taken into consideration. 9. There is no discussion about findings of the article, and conclusion is very vague. At the end of study, there is no comparison of the 9 compounds screened. Better compound should be identified and screened. Biological data to support the findings can be added, however it is not mandatory. Discussion section should be added and findings of each compound should be compared and correlated to previously done studies. 10. Discuss future prospects of this study, elaborate briefly what experimental studies should be done further and state the limitations of this 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?\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": "302514",
"date": "10 Oct 2024",
"name": "Shvetank Bhatt",
"expertise": [
"Reviewer Expertise CNS Diosrders",
"AD",
"Depression",
"Anxiety"
],
"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 is well written and can be accepted after minor modifications. 1. Author can highlight the names of drugs which are recently approved for the treatment of AD in introduction section. 2. Results and discussion section is presented well by authors. 3. Author should discuss the epidemiology and pathophysiology of diseases briefly to understand the severity of disease.\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/13-773
|
https://f1000research.com/articles/13-439/v1
|
02 May 24
|
{
"type": "Opinion Article",
"title": "There is no easy fix to peer review but paying referees and regulating the number of submissions might help",
"authors": [
"Mohamed L. Seghier"
],
"abstract": "The exponential increase in the number of submissions, further accelerated by generative AI, and the decline in the availability of experts are burdening the peer review process. This has led to high unethical desk rejection rates, a growing appeal for the publication of unreviewed preprints, and a worrying proliferation of predatory journals. The idea of monetarily compensating peer reviewers has been around for many years; maybe, it is time to take it seriously as one way to save the peer review process. Here, I argue that paying reviewers, when done in a fair and transparent way, is a viable solution. Like the case of professional language editors, part-time or full-time professional reviewers, managed by universities or for-profit companies, can be an integral part of modern peer review. Being a professional reviewer could be financially attractive to retired senior researchers and to researchers who enjoy evaluating papers but are not motivated to do so for free. Moreover, not all produced research needs to go through peer review, and thus persuading researchers to limit submissions to their most novel and useful research could also help bring submission volumes to manageable levels. Overall, this paper reckons that the problem is not the peer review process per se but rather its function within an academic ecosystem dominated by an unhealthy culture of ‘publish or perish’. Instead of reforming the peer review process, academia has to look for better science dissemination schemes that promote collaboration over competition, engagement over judgement, and research quality and sustainability over quantity.",
"keywords": [
"peer review",
"research disseminations",
"referees",
"publishers",
"scholarly communication",
"awards and incentives",
"professional reviewers"
],
"content": "Introduction\n\nThe peer review process has been the cornerstone of science dissemination for centuries.1,2 It can exist in different forms,3,4 all based on the elusive concepts of referees’ impartiality5 and competency.6 The peer review process is known to be slow, expensive, inconsistent, biased,3,7–11 and with limited impact on the quality of research publications.12,13 These limitations have led to some calls to completely abandon the whole process because “prepublication peer review is an enormous sink of scientists’ time, effort, and resources”.14 Despite the limitations, one can note that the research community has still strong faith in it7,15; i.e. “despite the limitations of peer review process, we need it. It is all we have, and it is hard to imagine how we could get along without it”.16 How to reform the peer review process has always been an extremely complex endeavor.17\n\nMany calls have been made to reform the peer review process, typically along four schools of thought according to Waltman (2023). Here, this review subscribes to the Efficiency & Incentives school that focuses on streamlining the peer review process and incentivizing participation in it.18 This is a completely pragmatic choice because without an efficient peer review system there is no point in my opinion of discussing its quality, reproducibility, transparency or inclusion. Those qualities, promoted by other schools of thoughts, are extremely important but they are contingent to the suitability of the existing system to cope with current research productivity levels of millions of scientific articles.19 Specifically, over 2.5 million papers are published each year in English alone,20 creating an incredible burden on editors and reviewers. The problem is obvious to all stakeholders: the exponential increase in the number of manuscripts largely surpasses the current availability of qualified referees. Put another way, the current peer review process is not well equipped to serve modern publication dynamics that are expected to accelerate even more in this era of generative AI.\n\nIt might be useful to contemplate what could be the alternative if no adequate and sustainable solutions are found. As nature abhors a vacuum, if the current peer review model is not reformed, frustrated authors will have to rely on other means to get their studies out, in particular when desk rejection rates in reputable journals are reaching high rates. This might for instance lead to a surge in alternative models based on the publication of unreviewed preprints, or the creation of local journals or repositories owned and managed by the authors’ universities and research institutions.21 However, the biggest risk is the undesirable proliferation of predatory journals offering a “pay-to-publish” model sometimes without peer review.22–24 I believe that models based on pre-publication peer-review are still useful as they do serve the interest of science relatively better than other models. In that context, I discuss here the idea of promoting the role of professional reviewers, like professional editors, who will be monetarily compensated for their role in the peer-review process.\n\n\nNo more motivation to review for free\n\nBelow, I describe a concrete situation based on my own experience as editor-in-chief of a scientific journal. The journal I’m editing, as it might be the case for other journals, is experiencing a (welcome) growth in number of submissions that is putting too much pressure on an already overstretched peer review process.25 Consequently, this situation has resulted in (1) an unethical increase in desk rejection rates, (2) a low percentage of invited researchers willing to review papers, (3) an increase in the number of papers rejected after being sent for peer-review due to the difficulty to secure two or more referee reports, (4) referees not submitting their reports after initially agreeing to do so, (5) referees submitting scant reports, listing superficial, unhelpful, or even irrelevant comments and suggestions, and (6) an increase in instances of fraud where for example false contact information of potential referees with non-institutional emails are suggested or when the peer review process has been manipulated. All these issues are directly or indirectly related to the pressure to ensure fair and rigorous peer review process when the main players (reviewers) are no longer motivated to give away their time and expertise for free.\n\nIn this context, a wide range of solutions and innovations have been proposed in the past (see analytical review in26) to address the non-availability of volunteer peer reviewers.26–30 Table 1 provides a succinct summary of some proposed innovations in current literature. This includes for instance a more efficient involvement of editors in the selection of prospective reviewers,31 improving diversity,32 training reviewers and opening up the peer review process.7 Others have argued that peer reviewers are rejecting invitations not necessarily because of lack of time but presumably because of lack of motivation.33 Therefore, rewarding reviewers can help increase thier (extrinsic) motivation, like offering certificates, discounts on publisher’s products, and publicly acknowledging the best and the most productive reviewers.33,34\n\nA list of suggested solutions and innovations in previous studies. Paying professional reviewers can be implemented in conjunction with any of the solutions below.\n\nHowever, these suggestions might not solve existing problems for four main reasons: (i) the number of submissions is projected to increase at much faster rates in this era of generative AI, (ii) the traditional job of academia is being transformed with extra roles that researchers are expected to assume, leaving no time for reviewing papers, including admin duties, seeking funds, leadership roles, academic advising, organizing outreach activities in the community, and working on translating their research into marketable solutions, (iii) the number of journals and publications in other languages than English is growing fast, promoted by current initiatives to improve inclusion in science dissemination, which makes it challenging to ensure a rigorous multilingual peer review process, (iv) researchers are increasingly unsatisfied with for-profit publishers that have made exorbitant profits with negligible contribution to research in general, resulting in many researchers not keen to review for for-profit journals, and (v) perhaps most importantly, researchers are likely to become less willing to spend time on reviewing AI-enhanced quick-to-write papers (e.g. when the time taken to review a paper becomes longer than the time taken to draft that paper with AI). I believe the latter is likely to be increasingly present in the debate about reforming the peer review process, which is why monetary incentives might be one potential means to alleviate the burden on the peer review process to some extent.\n\n\nToward the promotion of Professional Reviewer as a career\n\nPublishing research articles is still an expensive business even in this digital era.35–37 The global annual cost of peer-review is estimated at around $1.5 billion,38 corresponding to a net annual contribution of over 100 million hours by reviewers.39 In the current science dissemination business evaluated at billions of dollars, peer reviewers are still providing volunteer labour. Journals should thus develop methods to compensate reviewers for their time while maintaining the integrity of the peer-review process.38,40 The system needs fair and sustainable mechanisms to pay referees. This would allow researchers to earn money by becoming full-time or part-time professional reviewers. Like the remunerated role played by professional language editors, researchers who enjoy evaluating research papers can be invited to dedicate more time to the peer review process for a fee.41 For instance, a professional reviewer can be tasked with reviewing a given number of papers per week (e.g. 2 or 3 papers/week), which would help speed up the peer review process in particular for journals with large submission volumes.\n\nWe already have models where referees are paid for reviewing academic work, as grant reviewers, PhD examiners, or academic promotion examiners. Reviewing articles is no exception and could thus be considered as a remunerated task in academia. There is room for the emergence of two different but complementary professional reviewers. Reviewers can still be academicians, working in universities and research institutions, where they can be offered the opportunity to supplement their salaries with additional honorariums for their active involvement in the peer review process. Another alternative concerns the possibility to outsource the peer review process by allowing the creation of independent providers. These providers, managed by for-profit companies,42 can follow the same work model as companies that employ professional language editors in research dissemination. The job of a professional reviewer can be regulated by adopting new ethical and professional standards to safeguard the peer review process from any possible unethical practices that might occur when money is involved in the process (Figure 1).\n\nA typical publication process that involves professional reviewers. It shows the different steps (blue boxes) and their implementation in a fair and transparent way (green boxes).\n\nThe proponent of this idea argues that per review should be considered as a business transaction,43 where a modest remuneration per paper of around 200$43, or $450 for for-profit publishers,44 can be offered to reviewers. This can motivate reviewers to be more actively involved in the peer review process and to offer fast and thorough review reports.45,46 This can also be an incentive for retired scientists43,47 to participate in order to gain an extra income that expands their retirement plans. Paying referees can increase the pool of available reviewers, including for instance researchers who cannot afford to work for free.47 Below, I discuss some options to sustain the payment of professional referees.\n\nReviewers as consultants: Researchers are usually invited to budget for the support of a consultant or a technical expert when applying for grants. For instance, the consultant can provide expert opinion about an aspect of the research project that might be beyond the expertise of the researchers (e.g. a legal advisor, an industrial partner, a clinical professional, a computer system expert, a programmer, … etc). In the same way, a peer reviewer can be seen as a consultant whose role is to support the researchers in improving their papers in terms of readability, quality, and methodological soundness. Publications are typically included as deliverables in research grants, and therefore the contribution of peer reviewers to improve these deliverables can be budgeted as consultancy fees. However, this option might put too much financial burden on funding bodies as they are already covering the excessive article-processing charges of publications. Similar to some alternatives being sought for article-processing charges payments,48 funding bodies should also work closely with publishers to make the payment process of professional reviewers as fair and transparent as possible, in particular when for-profit agencies are managing the peer review process.\n\nLevying a submission fee: As it is practice in some journals, a submission fee can be collected for each submitted article, which can then be used to pay professional reviewers. For example, around 45 of the economics, finance and accounting journals published by Elsevier charge a submission fee of around $50-$100. Likewise, some biology journals also levy submission fees. Their rationale is to ensure that only within-scope and high-quality papers are received. Submission fees also serve other purposes like sponsoring conferences and workshops, the payment of language editing services, prizes/awards such as the annual best paper award, and even payments to top reviewers. To make payment of professional reviewers sustainable, it might be suggested to levy a submission fee of $200 per submitted paper. This fee should only be charged for submissions sent for review. I believe a $200 would be a fair submission fee for the service of getting constructive comments about how to improve a paper. For example, a journal with a submission volume of 1,000 papers per year, and a desk-rejection rate of 50%, the collected submission fees (around $100,000) can help secure the services of professional reviewers. To make this option attractive for authors, the submission fee should be deduced from the article-processing charges or the open access fee once the peer-reviewed paper is accepted. Consequently, this might mean that publishers should consider reducing their article processing charges when levying a submission fee, as discussed below.\n\nPaying referees in the context of economic disparity: One of the consequences of paying reviewers might be a better diversity in peer review. This is because paying referees might be very appealing for researchers from low- or middle-income countries. However, this monetary incentive can inadvertently yield over-involvement in the peer review process because a fee of 200$ or more is sometimes comparable to a full salary in some low-income countries. Put another way, researchers from low-income countries can favour paid peer review over other academic duties, which might not be a tenable situation for their institutions. One way to avoid this race for more reviews, and hence more money, is to link the number of invitations for referees from low-income countries to the size of authors or readers from those low-income countries. For instance, if a journal has a readership of 20% from low-income countries, the number of invited referees from low-income countries can be capped at twice this percentage. Furthermore, all paid review tasks should be declared on the publisher’s website so that editors are well informed about the level of involvement of different referees. This would help identify any unusual review dynamics that need adjustments to ensure a fair and robust peer review.\n\nHow about the publishers? There is a clear dissatisfaction from academia about the ‘parasitic’ behaviour of some for-profit publishers in research dissemination. They are seen as the biggest winners of the current system despite not funding research and not paying the original content creators (the authors) and evaluators (the reviewers).49 Recent examples of editors quitting for-profit journals provide an interesting example to grasp with the depth of that dissatisfaction (e.g. Refs. 50, 51). My own reading of the publication landscape makes me believe that for-profit publishers, if they do not engage with the research community in a more honest and constructive way, will soon be made irrelevant to the whole process. It is important that publishers realize that they cannot continue operating along the same model. The least one can expect from them is to inject some of their profits back to the peer review process. However, it is unlikely that publishers would be willing to financially contribute to the peer review process unless they have control on the process through the creation of their own professional review agencies. However, I don’t think the research community can again trust for-profit publishers with the peer review process, which is understandable given the previous experience of the community with the open access model that has unfortunately been made so expensive and unaffordable by some for-profit publishers.\n\nIn this context, I feel that research dissemination might foreseeably follow a radical model by completely bypassing for-profit publishers, i.e. a model that does not need the ‘middleman’. This implies that researchers and their universities will soon own the whole process of research dissemination.52 In this model, universities and research institutions might chose to manage the whole publication process, for instance in the form of posting papers on open repositories,53 while adopting an open post-publication peer review model. Universities can work as consortia to share the cost of publication through common or shared repositories. The other implication here is to allow researchers (or their institutions) keep intellectual property of their work instead of conceding it to publishers as in the current model.\n\nArguments against paying peer reviewers: The opponents to paying reviewers mention the risks of proliferation of unethical practices (i.e. the system to be corrupted by money) and unsustainable costs44,47,54 as it can lead to increases in subscription fees and article processing charges.55 Moreover, adding a monetary component to the peer review might lead to unethical practices to maximize the number of completed reviews such as non-disclosure of conflict of interest, the tendency to review papers even outside one’s domain of expertise, and a fast turnaround time with no through evaluation of the reviewed papers. Therefore, it is important to put some safeguards to ensure high quality and rigorous peer review process, for instance, through the evaluation/rating by the editors of completed reviews before approving payment to the referees.\n\nLikewise, paying reviewers might yield a proliferation of for-profit peer review agencies with dubious ethical practices, like paper mills, that can generate fabricated review reports.55 Some studies have argued that monetary rewards tend to decrease the quality of the peer review process56 as well as the intrinsic motivation of researchers to contribute to the peer review process.57 Paying reviewers might be only sustainable for journals with a reasonable submission volume.58 For multidisciplinary journals with broad topics and large submission volumes, the peer review process can be enormously costly and thus diverse funding sources have to be sought. There is also the risk that paying referees will soon become the norm, making researchers no longer interested to review for free. It could also lead to a multi-tier peer review system depending on how much a journal chose to pay its reviewers, hence engendering an unequal competition between journals for the service of reviewers. Overall, although one cannot rule out the risk of corruption in peer review by money, I trust that academia has in-built mechanisms to handle financial transactions in a fair and objective way as it is the case when researchers are paid for evaluating grant proposals and academic theses.47\n\nOther schemes of financial compensations: It might be worth mentioning other alternative models to professional reviewers. For example, one proposal argues for offering monetary compensations not for the reviewers themselves but their institutions59 as they usually deal with the same publishers for purchasing subscriptions and other products. The rationale is that reviewers are already paid by their institutions and hence their involvement in the peer review process should benefit their institutions. However, this sometime ignores the fact that researchers sometimes (often?) conduct their reviews outside work hours (e.g. evenings or weekends), and hence their contributions to peer review should not be assumed already covered by their salaries. Likewise, another similar recent proposal argues for monetary prizes not to individual referees but to their groups (departments, research units or labs).57 That collected money for instance can support ongoing research projects, support early career members or the work of members from underrepresented minorities.57\n\n\nPeer review cannot thrive in the current academic ecosystem\n\nThe above-mentioned solutions are assumed remedies to a malfunctional peer review process. But maybe the whole peer review process is fine, and all encountered problems are due to the fact that peer review is operating within the wrong environment. Indeed, the culprit here is the current academic environment that promotes an unhealthy culture of “publish or perish”. To survive in this culture, it is not unusual that researchers do fragment their results into multiple publications or even publish redundant papers based on similar data.30,60 This culture of “publish or perish” is hurting academic research.61 Therefore, instead of instigating calls to abandon or reform the peer review process, academia should invent and campaign for new models that departs from the “publish or perish” model.62 As long as research quality is measured as a function of research productivity, there will be no form of peer review that can guarantee quality research while dealing with a deluge of papers that is now being inflated even more by the adoption of generative AI.\n\nIs the ultimate goal of academia to produce prolific researchers who can publish two or more papers a week, sometimes with questionable practices.63 If, hypothetically, this goal is achieved by every researcher, who would review (and read) the published work? In fact, evidence shows that many published papers remain uncited or end up having little impact on their respective fields, but one cannot ignore the resources those papers took (time and effort) from reviewers and editors. It is as if the whole purpose of many substandard papers is to inflate some research metrics. Can academia promote a new model that puts a cap on how many papers an author can submit per year? This is essentially to invite researchers to think sensibly about the quality of their research and maybe only publish the best of their research that is likely to have an impact on the knowledge creation enterprise. Other work can still be shared as unreviewed preprints.64 This framework ensures a manageable number of submissions, though it might entail a rethinking of current citation-based metrics of research impact and productivity.\n\n\nConclusion\n\nWe can’t afford to ignore existing flaws in the current peer review system because the status quo will only favour the emergence of unethical practices. Here, I support the idea, albeit not new, of the creation of professional peer reviewers. Paying reviewers must be made in a fair and transparent way. Future work needs to investigate alternative ways to ensure a sustainable and affordable remuneration of professional reviewers. The discussion should continue among all stakeholders to identify new solutions and innovations for an efficient and affordable research dissemination in the modern era of generative AI. Empowering universities and research institutions to own the whole research dissemination system might soon be an inevitable scheme to consider. Finally, without reforming academia when it comes to disseminating the work of its members, research dissemination will continue relying on a costly and ineffective peer review system that will soon or later be completely abandoned or replaced by something else.\n\n\nContributions\n\nThis opinion article was conceived and written by MLS.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nCastillo M: Peer review: past, present, and future. AJNR Am. J. Neuroradiol. 2012; 33(10): 1833–1835. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSpier R: The history of the peer-review process. Trends Biotechnol. 2002; 20(8): 357–358. Publisher Full Text\n\nJubb M: Peer review: The current landscape and future trends. Learn. Publ. 2016; 29(1): 13–21. Publisher Full Text\n\nKoshy K, Fowler AJ, Gundogan B, et al.: Peer review in scholarly publishing part A: why do it? Int. J. Surg. Oncol. 2018; 3(2): e56. Publisher Full Text\n\nAtkinson M: Regulation of Science by “Peer Review”. Stud. Hist. Phil. Sci. 1994; 25: 147–158. Publisher Full Text\n\nBaxt WG, Waeckerle JF, Berlin JA, et al.: Who reviews the reviewers? Feasibility of using a fictitious manuscript to evaluate peer reviewer performance. Ann. Emerg. Med. 1998; 32(3 Pt 1): 310–317. PubMed Abstract | Publisher Full Text\n\nSmith R: Peer review: a flawed process at the heart of science and journals. J. R. Soc. Med. 2006; 99(4): 178–182. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWalker R, Rocha da Silva P: Emerging trends in peer review-a survey. Front. Neurosci. 2015; 9: 169.\n\nHaffar S, Bazerbachi F, Murad MH: Peer Review Bias: A Critical Review. Mayo Clin. Proc. 2019; 94(4): 670–676. PubMed Abstract | Publisher Full Text\n\nvan Rooyen S : A critical examination of the peer review process. Learn. Publ. 1998; 11(3): 185–191. Publisher Full Text\n\nWilliamson A: What will happen to peer review? Learn. Publ. 2003; 16(1): 15–20. Publisher Full Text\n\nJefferson T, Wager E, Davidoff F: Measuring the quality of editorial peer review. JAMA. 2002; 287(21): 2786–2790. Publisher Full Text\n\nWager E, Jefferson T: Shortcomings of peer review in biomedical journals. Learn. Publ. 2001; 14(4): 257–263. Publisher Full Text\n\nHeesen R, Bright LK: Is Peer Review a Good Idea? Br. J. Philos. Sci. 2021; 72(3): 635–663. Publisher Full Text\n\nJefferson T, Alderson P, Wager E, et al.: Effects of editorial peer review: a systematic review. JAMA. 2002; 287(21): 2784–2786. Publisher Full Text\n\nRelman AS: Peer review in scientific journals--what good is it? West. J. Med. 1990; 153(5): 520–522. PubMed Abstract\n\nChloros GD, Giannoudis VP, Giannoudis PV: Peer-reviewing in Surgical Journals: Revolutionize or Perish? Ann. Surg. 2022; 275(1): e82–e90. Publisher Full Text\n\nWaltman L, Kaltenbrunner W, Pinfield S, et al.: How to improve scientific peer review: Four schools of thought. Learn. Publ. 2023; 36(3): 334–347. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJinha AE: Article 50 million: an estimate of the number of scholarly articles in existence. Learn. Publ. 2010; 23(3): 258–263. Publisher Full Text\n\nTennant JP: The state of the art in peer review. FEMS Microbiol. Lett. 2018; 365(19). PubMed Abstract | Publisher Full Text | Free Full Text\n\nGogotsi Y: Pay to publish? Open access publishing from the viewpoint of a scientist and editor. Graphene 2D Mater. 2023; 8: 1–3. Publisher Full Text\n\nCamargo LM, Smirnov M, Maldonado IL: The prey’s perspective on the rise of predatory publishing. EXCLI J. 2023; 22: 904–906. PubMed Abstract | Publisher Full Text\n\nGrudniewicz A, Moher D, Cobey KD, et al.: Predatory journals: no definition, no defence. Nature. 2019; 576(7786): 210–212. PubMed Abstract | Publisher Full Text\n\nMertkan S, Onurkan G, Nilgun Suphi G: Profile of authors publishing in ‘predatory’ journals and causal factors behind their decision: A systematic review. Res. Eval. 2021; 30(4): 470–483. Publisher Full Text\n\nSeghier ML: Demystifying desk rejection: A call to action for our authors. Int. J. Imaging Syst. Technol. 2022; 32(3): 701–703. Publisher Full Text\n\nKaltenbrunner W, Pinfield S, Waltman L, et al.: Innovating peer review, reconfiguring scholarly communication: an analytical overview of ongoing peer review innovation activities. J. Doc. 2022; 78(7): 429–449. Publisher Full Text\n\nWoods HB, Brumberg J, Kaltenbrunner W, et al.: An overview of innovations in the external peer review of journal manuscripts. Wellcome Open Res. 2022; 7: 82. Publisher Full Text\n\nSpier RE: Peer review and innovation. Sci. Eng. Ethics. 2002; 8(1): p. 99–108. discussion 109-12. Publisher Full Text\n\nBarroga E: Innovative Strategies for Peer Review. J. Korean Med. Sci. 2020; 35(20): e138. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStahel PF, Moore EE: Peer review for biomedical publications: we can improve the system. BMC Med. 2014; 12: 179. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZupanc GKH: “It is becoming increasingly difficult to find reviewers”—myths and facts about peer review. J. Comp. Physiol. A. 2023; 210: 1–5. in press. Publisher Full Text\n\nBen Messaoud K, Schroter S, Richards M, et al.: Analysis of peer reviewers’ response to invitations by gender and geographical region: cohort study of manuscripts reviewed at 21 biomedical journals before and during covid-19 pandemic. BMJ. 2023; 381: e075719. Publisher Full Text\n\nEllwanger JH, Chies JAB: We need to talk about peer-review-Experienced reviewers are not endangered species, but they need motivation. J. Clin. Epidemiol. 2020; 125: 201–205. PubMed Abstract | Publisher Full Text\n\nKünzli N, Berger A, Czabanowska K, et al.: «I Do Not Have Time»—Is This the End of Peer Review in Public Health Sciences? Public Health Rev. 2022; 43: 1605407. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGrossmann A, Brembs B: Current market rates for scholarly publishing services [version 2; peer review: 2 approved]. F1000Res. 2021; 10: 20. Publisher Full Text\n\nSmart P: Peer review: An expensive business. Learn. Publ. 2016; 29: 3–4. Publisher Full Text\n\nDonovan B: The truth about peer review. Learn. Publ. 1998; 11(3): 179–184. Publisher Full Text\n\nLeBlanc AG, Barnes JD, Saunders TJ, et al.: Scientific sinkhole: estimating the cost of peer review based on survey data with snowball sampling. Res. Integr. Peer Rev. 2023; 8(1): 3. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAczel B, Szaszi B, Holcombe AO: A billion-dollar donation: estimating the cost of researchers’ time spent on peer review. Res. Integr. Peer Rev. 2021; 6(1): 14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGasparyan AY, Gerasimov AN, Voronov AA, et al.: Rewarding peer reviewers: maintaining the integrity of science communication. J. Korean Med. Sci. 2015; 30(4): 360–364. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOtt S, Hebenstreit D: Supply and demand: Apply market forces to peer review. Nature. 2014; 506(7488): 295. PubMed Abstract | Publisher Full Text\n\nVan Noorden R: Company offers portable peer review. Nature. 2013; 494(7436): 161. PubMed Abstract | Publisher Full Text\n\nDiamandis EP: Publishing costs: Peer review as a business transaction. Nature. 2015; 517(7533): 145. PubMed Abstract | Publisher Full Text\n\nBrainard J: The $450 question: Should journals pay peer reviewers? Science. 2021. Publisher Full Text\n\nHamermesh DS: Facts and Myths about Refereeing. J. Econ. Perspect. 1994; 8(1): 153–163. Publisher Full Text\n\nThompson GD, Aradhyula SV, Frisvold G, et al.: Does Paying Referees Expedite Reviews?: Results of a Natural Experiment. South. Econ. J. 2010; 76(3): 678–692. Publisher Full Text\n\nCheah PY, Piasecki J: Should peer reviewers be paid to review academic papers? Lancet. 2022; 399(10335): 1601. PubMed Abstract | Publisher Full Text\n\nSanderson K: Who should pay for open-access publishing? APC alternatives emerge. Nature. 2023; 623(7987): 472–473. PubMed Abstract | Publisher Full Text\n\nWalter P, Mullins D: From symbiont to parasite: the evolution of for-profit science publishing. Mol. Biol. Cell. 2019; 30(20): 2537–2542. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSanderson K: Editors quit top neuroscience journal to protest against open-access charges. Nature. 2023; 616(7958): 641. PubMed Abstract | Publisher Full Text\n\nSingh Chawla D: Open-access row prompts editorial board of Elsevier journal to resign. Nature. 2019. Publisher Full Text\n\nRoh C: Owning the peer review process. Coll. Res. Libr. News. 2022; 83(3). Publisher Full Text\n\nTorres L, Hartley R: Repositories for academic products/outputs: Latin American and Chilean visions. F1000Res. 2019; 8: 1517. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGropp RE, Glisson S, Gallo S, et al.: Peer Review: A System under Stress. Bioscience. 2017; 67(5): 407–410. Publisher Full Text\n\nMoustafa K: No to paid peer review. Lancet. 2022; 400(10347): 160. Publisher Full Text\n\nSquazzoni F, Bravo G, Takacs K: Does incentive provision increase the quality of peer review? An experimental study. Res. Policy. 2013; 42(1): 287–294. Publisher Full Text\n\nBonaccorsi A: Towards Peer Review As a Group Engagement. JLIS. It. 2022; 14(1): 46–59. Publisher Full Text\n\nChang J-J, Lai C-C: Is It Worthwhile to Pay Referees? South. Econ. J. 2001; 68(2): 457–463.\n\nCopiello S: On the money value of peer review. Scientometrics. 2018; 115: 613–620. Publisher Full Text\n\nBeaufils P, Karlsson J: Legitimate division of large datasets, salami slicing and dual publication. Where does a fraud begin? Orthop. Traumatol. Surg. Res. 2013; 99(2): 121–122. PubMed Abstract | Publisher Full Text\n\nRawat S, Meena S: Publish or perish: Where are we heading? J. Res. Med. Sci. 2014; 19(2): 87–89. PubMed Abstract\n\nYeo MA, Renandya WA, Tangkiengsirisin S: Re-envisioning Academic Publication: From “Publish or Perish” to “Publish and Flourish”. RELC J. 2022; 53(1): 266–275. Publisher Full Text\n\nIoannidis JPA, Collins TA, Baas J: Evolving patterns of extremely productive publishing behavior across science.2023. Preprint. Publisher Full Text\n\nArns M: Open access is tiring out peer reviewers. Nature. 2014; 515(7528): 467. PubMed Abstract | Publisher Full Text\n\nvan Rooyen S , Godlee F, Evans S, et al.: Effect of blinding and unmasking on the quality of peer review: a randomized trial. JAMA. 1998; 280(3): 234–237. PubMed Abstract | Publisher Full Text\n\nKennison R: Back to the future: (re) turning from peer review to peer engagement. Learn. Publ. 2016; 29(1): 69–71. Publisher Full Text\n\nRoss-Hellauer T: What is open peer review? A systematic review [version 2; peer review: 4 approved]. F1000Res. 2017; 6: 588. Publisher Full Text\n\nMarcoci A, Vercammen A, Bush M, et al.: Reimagining peer review as an expert elicitation process. BMC. Res. Notes. 2022; 15(1): 127. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBell GP, Kvajo M: Tackling waste in publishing through portable peer review. BMC Biol. 2018; 16(1): 146. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSpezi V, Wakeling S, Pinfield S, et al.: Open-Access mega-journals: The future of scholarly communication or academic dumping ground? A review. J. Doc. 2017; 73: 263–283. Publisher Full Text\n\nLing F: Improving peer review: increasing reviewer participation. Learn. Publ. 2011; 24: 231–233. Publisher Full Text\n\nPapatriantafyllou M: Peer Review - the future is here. FEBS Lett. 2017; 591(18): 2789–2792. Publisher Full Text\n\nKousha K, Thelwall M: Artificial intelligence to support publishing and peer review: A summary and review. Learn. Publ. 2024; 37: 4–12. (in press). Publisher Full Text\n\nHeaven D: AI peer reviewers unleashed to ease publishing grind. Nature. 2018; 563(7733): 609–610. PubMed Abstract | Publisher Full Text\n\nGraur D: Payback time for referee refusal. Nature. 2014; 505: 483. PubMed Abstract | Publisher Full Text\n\nLaxdal A, Haugen T: Where are the carrots? A proposal to start crediting peer reviewers for their contribution to science. Learn. Publ. 2024; 37: 154–156. (in press). Publisher Full Text\n\nGorin MA: Combating reviewer fatigue with carrots. BJUI Compass. 2023; 4(1): 3–4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKumar MN: The ‘peer reviewer as collaborator’ model for publishing. Learn. Publ. 2010; 23(1): 17–22. Publisher Full Text\n\nTeixeira da Silva JA, Dobranszki J: Problems with traditional science publishing and finding a wider niche for post-publication peer review. Account. Res. 2015; 22(1): 22–40. PubMed Abstract | Publisher Full Text\n\nTeixeira da Silva JA, Al-Khatib A, Dobranszki J: Fortifying the Corrective Nature of Post-publication Peer Review: Identifying Weaknesses, Use of Journal Clubs, and Rewarding Conscientious Behavior. Sci. Eng. Ethics. 2017; 23(4): 1213–1226. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "277016",
"date": "31 May 2024",
"name": "Balazs Aczel",
"expertise": [
"Reviewer Expertise metascience"
],
"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\nAll in all, I found that the manuscript discusses an important and timely topic along a well structured argument. My only major issue with the message of the paper is that it proposes paying referees as a solution to the peer review crisis although there are a number of listed and unresolved issues with the ideas. For example, the author shortly discusses that if paying reviewers becomes a norm then they might become uninterested in reviewing for free. This would be a very negative development for not-for-profit publishers, further strengthening the for-profit model that the author criticises. The author suggests that the budget for paying the reviewers could come from $200 submission fees which could be reduced from the article processing charges. Although it sounds like a fair solution, it would go against the publishers' financial interest since they would \"lose\" that income. From a profit-oriented point-of-view, it either makes the proposal sound unsavory unless the loss can be compensated by further increasing the APCs.\nMinor issues: - \" exponential increase in the number of submissions\", \"desk rejection rates in reputable journals are reaching high rates\" are factual statements without reference to evidence. - Among the potential solution could be mentioned PCI https://peercommunityin.org/ where the community organizes the reviews without any involvement of the journals. This model should reduce redundancies in the peer review system.\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": [
{
"c_id": "11889",
"date": "09 Jul 2024",
"name": "Mohamed Seghier",
"role": "Author Response",
"response": "Point-by-point responses: I would like to thank both reviewers for their very helpful and constructive comments. All their concerns have been addressed in this resubmitted revision. All changes are highlighted in the revised manuscript with track changes. Below, is a detailed point-by-point rebuttal addressing each reviewer’s comment. Reviewer #1: Balazs Aczel, Eotvos Lorand University, Budapest, Hungary. All in all, I found that the manuscript discusses an important and timely topic along a well-structured argument. Thank you very much for your positivity. I’m happy to read that you did find the current version important and well-structured. Reviewer #1, continued: My only major issue with the message of the paper is that it proposes paying referees as a solution to the peer review crisis although there are a number of listed and unresolved issues with the ideas. For example, the author shortly discusses that if paying reviewers becomes a norm then they might become uninterested in reviewing for free. This would be a very negative development for not-for-profit publishers, further strengthening the for-profit model that the author criticises. Response: Thank you for raising this important point. I have now added the following statement to clarify this issue on Page 10: “There is also the risk that paying referees will soon become the norm, making researchers no longer interested in reviewing for free. It could also lead to a multi-tier peer review system depending on how much a journal chooses to pay its reviewers, hence engendering an unequal competition among journals for the service of reviewers. This could hurt not-for-profit publishers that cannot afford an expensive peer review process. In that context, not-for-profit publishers must (i) diversify incentives on top of paying reviewers, (ii) nurture the intrinsic motivation of their readers to participate in peer review and serve their scientific community [67], (iii) seek alternative means to be subsidized [69], and (iv) foster strategic partnerships with all stakeholders to make not-for-profit journals the preferred model for open-access publicly-funded research. Overall, although one cannot rule out the risk of corruption in peer review by money, I trust that academia has built-in mechanisms to handle financial transactions fairly and objectively, similar to cases when researchers are paid to evaluate grant proposals and academic theses [53].” Reviewer #1, continued: The author suggests that the budget for paying the reviewers could come from $200 submission fees which could be reduced from the article processing charges. Although it sounds like a fair solution, it would go against the publishers' financial interest since they would \"lose\" that income. From a profit-oriented point-of-view, it either makes the proposal sound unsavory unless the loss can be compensated by further increasing the APCs. Response: I agree with the reviewer here. Accordingly, I have made the following changes: To Page 8, I have added: “However, this might sound unsavory for for-profit publishers and hence the community needs to create alternative models that would make publishers active contributors to peer review, as discussed below.” See also the new edited text in the section “What about the publishers?” (Page 9-10). Reviewer #1, continued: Minor issues: - \" exponential increase in the number of submissions\", \"desk rejection rates in reputable journals are reaching high rates\" are factual statements without reference to evidence. Response: Thank you for spotting these missing citations. I have now added the following references: Bornmann L, Haunschild R, Mutz R (2021) Growth rates of modern science: a latent piecewise growth curve approach to model publication numbers from established and new literature databases. Humanities and Social Sciences Communications, 8:224. Larsen PO, von Ins M (2010) The rate of growth in scientific publication and the decline in coverage provided by Science Citation Index. Scientometrics, 84:575-603. 10.1007/s11192-010-0202-z. Meyer HS, Durning SJ, Sklar DP, Maggio LA (2018) Making the First Cut: An Analysis of Academic Medicine Editors' Reasons for Not Sending Manuscripts Out for External Peer Review. Acad Med, 93:464-470. 10.1097/ACM.0000000000001860. Reviewer #1, continued: - Among the potential solution could be mentioned PCI https://peercommunityin.org/ where the community organizes the reviews without any involvement of the journals. This model should reduce redundancies in the peer review system. Response: Thank you for this very important suggestion. I have now added PCI to Table 1. Please see the new revised version of the resubmitted manuscript."
}
]
},
{
"id": "282627",
"date": "21 Jun 2024",
"name": "Farid Rahimi",
"expertise": [
"Reviewer Expertise Cell biology",
"neurodegeneration",
"inflammation",
"COVID-19",
"academic publishing and peer review."
],
"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\nDr Seghier has written a comprehensive narrative opinion piece on the peer-review process as it is an integral part of the academic ecosystem. Dr Seghier has highlighted the fundamental issues that challenge(d) the efficacy and efficiency of the peer-review process contemporarily (or historically) and argues for establishing a transparent system whereby peer reviewers could be financially rewarded and recompensed. De Seghier argues that capping the number of paper submissions may also help reform the peer-review process. I have listed my comments that I hope will help improve the opinion piece or open up the perspective to discussion. The manuscript is written relatively well; however, summarising the text will benefit the readers.\nMajor comments: I suggest adding the emergence of competing mega-journals or mega-publishers as another issue that may affect the peer-review process (in the Abstract). This was mentioned in Table 1 and in reference 70. I believe this is part of the problem.\nThe last statement of the Abstract contradicts the argument for reform. Please revise “Instead of reforming the peer-review process …” because the piece calls for reform.\nChange the somehow hypothetical, “It can exist …” to factual, “It exists …” or “Peer review is performed in different ways.” \nPlease note that the description of the traditional roles of academics includes or represents the mainstream tenured academics. However, peer-reviewing is undertaken by non-tenured staff and academics with relevant qualifications, experience, and expertise. Reviewers in this category (for example, postdoctoral scholars, senior technical officers, qualified research assistants, qualified laboratory managers, or PhD-qualified persons who have quit academia, qualified academics who are active in postgraduate teaching) undertake peer-review merely to serve the scientific community; however, they generally cannot claim academic promotions for their voluntary participation in the peer-review process (because they do not have grants or tenured positions in a faculty). Thus, financially rewarding them makes perfect sense for their service and inclusion. Such an understanding acknowledges the inclusivity of the peer review process.\nSimilarly, the suggestion of co-authorship and academic benefits and promotions is interesting as presented in the Table 1. However, this excludes those reviewers who are not tenured academics (as discussed above). Please revise the paragraph 2 in page 7 of 13 (PDF file) to remove the assumption or assertion that all reviewers are academicians. \nPlease note that the remuneration of $200 (in Table 1 and page 8 of 13) or $450 are prescriptive. Some reviewing tasks demand many valuable hours if done diligently. Larger pieces of work and larger manuscripts with complex data and messages will require more time for thorough assessment. A mechanism for determining this remuneration should be discussed instead of prescribing a fixed amount (many factors may interplay). Determining the remuneration may not be simple as suggested or alluded by the author in the context of low-income countries. If this is left with the publishers, or some publishers take on this initiative or control, the publication charges and profit reaping will increase by many folds. What body controls this is unimaginable.\nPlease revise the assumptions that the funding bodies cover the publication charges and how they should work closely with the publishers to establish a fair means of paying the reviewers. This is confusing to me because, as I understand, funding bodies provide the grants to the academics or the researchers. The latter then need to budget for publication charges out of their granted funds. I also understand that the funding bodies normally do not interact with the publishers that publish a funded project that was conducted by the funded researchers or academics. Funding bodies also do not interfere with the research plans or outcomes. \nPlease note that Publons does not exist anymore. Publons was a commercial website that provided a free service for academics to track, verify, and showcase their peer review and editorial contributions to academic journals. It was launched in 2012 but was bought by Clarivate Analytics in 2017. https://en.wikipedia.org/wiki/Publons.\nMinor comments: The title is wordy. Please consider rephrasing/summarizing, e.g., “Paying academic reviewers and regulating the number of submitted papers may help fix the peer-review process.” Or “Remunerating peer reviewers and restricting the number of submitted papers may help fix the peer-review process.”\nPlease rewrite “It might be useful to contemplate what could be the alternative if no adequate and sustainable solutions are found.” to remove the dummy subject “it” and the hypothetical nature of the statement and clarify the message. For example, “Finding adequate and sustainable alternative solutions will be useful [or “is needed”].”\nPlease revise and summarize the following sentence and juxtapose “include or including” with the roles or duties. For example, “the traditional job of academia is being transformed with extra roles that researchers are expected to assume, leaving no time for reviewing papers, including admin duties, seeking funds, leadership roles, academic advising, organizing outreach activities in the community, and working on translating their research into marketable solutions,” should be changed to “the roles and duties of the academics include administration, writing grants, writing papers, writing patents, commercialization ventures, leaderships and directorships, editorships, teaching, supervision, committee memberships, consultancy, and outreach, leaving no time for reviewing papers.”\nPlease change “in other languages than English” to “in languages other than English”.\nPlease summarize the following statement to remove repetitions: “researchers are increasingly unsatisfied with for-profit publishers that have made exorbitant profits with negligible contribution to research in general, resulting in many researchers not keen to review for for-profit journals”. For example, “academics and authors avoid peer-reviewing because they are increasingly unsatisfied with for-profit publishers that reap exorbitant profits while contribute negligibly towards academia and research.” While mentioning this, some journals or publishers sponsor conferences or provide thesis or paper prizes and competitions. However, the proportion of this contribution could be small. I’m not sure if this has been studied systematically. \nIn Table 1, revise the following: “basically based on” “Reviewers time” to “Reviewers’ time” “Add some delays to the publication of papers” to “Delays the publication” “Reviewers’ databases” “to oversight” to “to oversee” “Augment the peer process” to “Augment the review process” “are not Involved” to “are not involved”\nRephrase the subtitle, “Toward the promotion of Professional Reviewer as a career” to “Promoting professional reviewing as a career”. A review cannot be factually (logically) promoted as a career.\nPlease rephrase sentences that use dummy subjects, “it is,” “there is,” or “there are” as suggested by the principles of plain English and for the sake of brevity.\nPlease avoid personifications, for example, “… this paper reckons …” while the credit should go to the author.\nAvoid using the passive voice and nominalizations (using verbs as nouns requiring helper verbs). For example, “Many calls have been made to reform …”\nAvoid contractions in academic writing, e.g., “I’m.”\nCorrect the minor spelling mistakes: ‘chose’ [choose in two places] ‘through evaluation’ [thorough evaluation] between journals [among journals] add a question mark after ‘Is the ultimate …’, ‘will soon or later’ [will sooner or later] … The paper will benefit from proofreading, editing, and summarization. Thank you for the opportunity to review your work.\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? No\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? Yes",
"responses": [
{
"c_id": "11890",
"date": "09 Jul 2024",
"name": "Mohamed Seghier",
"role": "Author Response",
"response": "Point-by-point responses: I would like to thank both reviewers for their very helpful and constructive comments. All their concerns have been addressed in this resubmitted revision. All changes are highlighted in the revised manuscript with track changes. Below, is a detailed point-by-point rebuttal addressing each reviewer’s comment. Reviewer #2: Farid Rahimi, Australian National University, Canberra, Australian Capital Territory, Australia. Dr Seghier has written a comprehensive narrative opinion piece on the peer-review process as it is an integral part of the academic ecosystem. Dr Seghier has highlighted the fundamental issues that challenge(d) the efficacy and efficiency of the peer-review process contemporarily (or historically) and argues for establishing a transparent system whereby peer reviewers could be financially rewarded and recompensed. De Seghier argues that capping the number of paper submissions may also help reform the peer-review process. I have listed my comments that I hope will help improve the opinion piece or open up the perspective to discussion. The manuscript is written relatively well; however, summarising the text will benefit the readers. Thank you very much for your positivity and the very useful suggestions. Reviewer #2, continued: Major comments: I suggest adding the emergence of competing mega-journals or mega-publishers as another issue that may affect the peer-review process (in the Abstract). This was mentioned in Table 1 and in reference 70. I believe this is part of the problem. Response: Thank you for this very interesting suggestion. I have briefly mentioned this issue in the new version of the Abstract: “the emergence of competing mega-journals”. Reviewer #2, continued: The last statement of the Abstract contradicts the argument for reform. Please revise “Instead of reforming the peer-review process …” because the piece calls for reform. Response: I fully agree with the reviewer. Accordingly, I have deleted that statement from the Abstract. Reviewer #2, continued: Change the somehow hypothetical, “It can exist …” to factual, “It exists …” or “Peer review is performed in different ways.” Response: Done! Thank you. Reviewer #2, continued: Please note that the description of the traditional roles of academics includes or represents the mainstream tenured academics. However, peer-reviewing is undertaken by non-tenured staff and academics with relevant qualifications, experience, and expertise. Reviewers in this category (for example, postdoctoral scholars, senior technical officers, qualified research assistants, qualified laboratory managers, or PhD-qualified persons who have quit academia, qualified academics who are active in postgraduate teaching) undertake peer-review merely to serve the scientific community; however, they generally cannot claim academic promotions for their voluntary participation in the peer-review process (because they do not have grants or tenured positions in a faculty). Thus, financially rewarding them makes perfect sense for their service and inclusion. Such an understanding acknowledges the inclusivity of the peer review process. Similarly, the suggestion of co-authorship and academic benefits and promotions is interesting as presented in the Table 1. However, this excludes those reviewers who are not tenured academics (as discussed above). Please revise the paragraph 2 in page 7 of 13 (PDF file) to remove the assumption or assertion that all reviewers are academicians. Response: Thank you for raising this important point. Accordingly, I have made the following changes: To Table 1: I have added this brief statement: “However, this model might exclude those reviewers who are not tenured academics.”. To Page 6, the edited text now reads: “Furthermore, peer-reviewing is also undertaken by non-tenured staff and academics with relevant qualifications and expertise (i.e. postdocs, senior technical staff, research assistants, laboratory engineers and managers, and PhD-qualified persons who have quit academia). However, they generally cannot claim academic promotions for their voluntary participation in the peer-review process. Thus, an inclusive peer review process must acknowledge their contributions by financially rewarding them.” Reviewer #2, continued: Please note that the remuneration of $200 (in Table 1 and page 8 of 13) or $450 are prescriptive. Some reviewing tasks demand many valuable hours if done diligently. Larger pieces of work and larger manuscripts with complex data and messages will require more time for thorough assessment. A mechanism for determining this remuneration should be discussed instead of prescribing a fixed amount (many factors may interplay). Determining the remuneration may not be simple as suggested or alluded by the author in the context of low-income countries. If this is left with the publishers, or some publishers take on this initiative or control, the publication charges and profit reaping will increase by many folds. What body controls this is unimaginable. Response: Thank you for raising this important point. The two figures ($200 and $450) were in fact suggested in prior work. I agree that many factors influence the level of remuneration, and I don’t think that a single mechanism can determine the exact remuneration for so many journals in very diverse domains. Having said that, I have added the following paragraph to Page 7: “Many factors may interplay to determine the level of remuneration [45, 54, 55], including reviewing for not-for-profit versus for-profit journals, scientific domains (e.g. research in medicine is more funded and expensive than research in art and humanities), the number of reviewers required per manuscript (e.g. two or more referees), the type of articles (e.g. reviewing a research article requires more hours than a commentary), and their length and complexity (e.g. reviewing a long review article or a full research article with complex data is more demanding than an opinion piece). Publishers and editors should estimate the level of remuneration according to the average hours typically spent by referees for each article type [45] and the average yearly number of manuscripts reviewed by each reviewer [36, 55]. Other organizations and agencies can also establish general guidelines about the payment of reviewers, including the Committee on Publication Ethics, the Declaration on Research Assessment, the Confederation of Open Access Repositories, and the European Association of Science Editors.” Reviewer #2, continued: Please revise the assumptions that the funding bodies cover the publication charges and how they should work closely with the publishers to establish a fair means of paying the reviewers. This is confusing to me because, as I understand, funding bodies provide the grants to the academics or the researchers. The latter then need to budget for publication charges out of their granted funds. I also understand that the funding bodies normally do not interact with the publishers that publish a funded project that was conducted by the funded researchers or academics. Funding bodies also do not interfere with the research plans or outcomes. Response: Thank you for allowing me to clarify this statement. Accordingly, I have edited that paragraph as below (see Page 7): “Publications are typically included as deliverables in research grants, and therefore the contribution of peer reviewers to improve these deliverables can be budgeted under the category of consultancy fees. Funding bodies may categorize this type of expense as publication fees. However, regardless of how paying reviewers is included in the budget, too much financial burden will be put on funding bodies as they are already covering the excessive article-processing charges. As alternatives are being sought for article-processing charges [56], funding bodies should put in place guidelines to make the payment process of professional reviewers as fair and transparent as possible, in particular when for-profit agencies are managing the peer review process. For instance, many funding bodies already require that published work must be made freely available, and thus similar requirements can also be made about the type of peer review (free or paid). If there is strong evidence that paying reviewers improves the quality of publications, then funding bodies can recommend researchers to publish in journals that pay referees. This ensures that funded research is being evaluated and scrutinized by the most rigorous review process that scholarly communication can offer (and afford).” Reviewer #2, continued: Please note that Publons does not exist anymore. Publons was a commercial website that provided a free service for academics to track, verify, and showcase their peer review and editorial contributions to academic journals. It was launched in 2012 but was bought by Clarivate Analytics in 2017. https://en.wikipedia.org/wiki/Publons. Response: Although the brand name Publons ceased to exist, some of its functionalities are still available via Web of Science. To avoid any confusion, I have now deleted it from Table 1. Reviewer #2, continued: Minor comments: The title is wordy. Please consider rephrasing/summarizing, e.g., “Paying academic reviewers and regulating the number of submitted papers may help fix the peer-review process.” Or “Remunerating peer reviewers and restricting the number of submitted papers may help fix the peer-review process.” Response: As suggested by the reviewer, I have now added the following new title: “Paying reviewers and regulating the number of papers may help fix the peer-review process”. Reviewer #2, continued: Please rewrite “It might be useful to contemplate what could be the alternative if no adequate and sustainable solutions are found.” to remove the dummy subject “it” and the hypothetical nature of the statement and clarify the message. For example, “Finding adequate and sustainable alternative solutions will be useful [or “is needed”].” Response: This statement has been rewritten as recommended by the reviewer; see Page 3. Reviewer #2, continued: Please revise and summarize the following sentence and juxtapose “include or including” with the roles or duties. For example, “the traditional job of academia is being transformed with extra roles that researchers are expected to assume, leaving no time for reviewing papers, including admin duties, seeking funds, leadership roles, academic advising, organizing outreach activities in the community, and working on translating their research into marketable solutions,” should be changed to “the roles and duties of the academics include administration, writing grants, writing papers, writing patents, commercialization ventures, leaderships and directorships, editorships, teaching, supervision, committee memberships, consultancy, and outreach, leaving no time for reviewing papers.” Response: Thank you for this suggestion. I have added it to Page 5 of the new revised version. Reviewer #2, continued: Please change “in other languages than English” to “in languages other than English”. Response: Done! Thank you. Reviewer #2, continued: Please summarize the following statement to remove repetitions: “researchers are increasingly unsatisfied with for-profit publishers that have made exorbitant profits with negligible contribution to research in general, resulting in many researchers not keen to review for for-profit journals”. For example, “academics and authors avoid peer-reviewing because they are increasingly unsatisfied with for-profit publishers that reap exorbitant profits while contribute negligibly towards academia and research.” While mentioning this, some journals or publishers sponsor conferences or provide thesis or paper prizes and competitions. However, the proportion of this contribution could be small. I’m not sure if this has been studied systematically. Response: I have replaced that statement with the reviewer’s suggestion (see Page 5 of the new revised version). Regarding your second point, I’m not aware of any systematic analysis of the contribution of for-profit publishers to scholarly communication. While they do sponsor some academic events, I believe this is a small fraction of what they get as profits (e.g. according to some estimations, Elsevier for instance has a 40% profit margin on its $2 Billion annual revenue). I did not mention this point in the revised version because it is extremely hard to get the exact figures when it comes to the money made or spent by publishers. Reviewer #2, continued: In Table 1, revise the following: “basically based on” “Reviewers time” to “Reviewers’ time” “Add some delays to the publication of papers” to “Delays the publication” “Reviewers’ databases” “to oversight” to “to oversee” “Augment the peer process” to “Augment the review process” “are not Involved” to “are not involved” Response: Done! Thank you for being meticulous here. Reviewer #2, continued: Rephrase the subtitle, “Toward the promotion of Professional Reviewer as a career” to “Promoting professional reviewing as a career”. A review cannot be factually (logically) promoted as a career. Response: Thank you for your suggestion. I have changed the subheading accordingly. Reviewer #2, continued: Please rephrase sentences that use dummy subjects, “it is,” “there is,” or “there are” as suggested by the principles of plain English and for the sake of brevity. Response: Thank you. I have removed many instances of “it is” and “there is”. Reviewer #2, continued: Please avoid personifications, for example, “… this paper reckons …” while the credit should go to the author. Response: This is now replaced by “I reckon …”. Thank you Reviewer #2, continued: Avoid using the passive voice and nominalizations (using verbs as nouns requiring helper verbs). For example, “Many calls have been made to reform …” Response: I have now reduced the occurrence of passive forms (has/have been). Thank you. Reviewer #2, continued: Avoid contractions in academic writing, e.g., “I’m.” Response: Done! Thank you. Reviewer #2, continued: Correct the minor spelling mistakes: ‘chose’ [choose in two places] ‘through evaluation’ [thorough evaluation] between journals [among journals] add a question mark after ‘Is the ultimate …’, ‘will soon or later’ [will sooner or later] … Response: Done! Thank you. Reviewer #2, continued: The paper will benefit from proofreading, editing, and summarization. Thank you for the opportunity to review your work. Response: I have edited the manuscript to correct any typing or grammatical errors. Thank you again for all these very useful and constructive comments and suggestions."
}
]
},
{
"id": "282628",
"date": "02 Jul 2024",
"name": "Vinícius Medina Kern",
"expertise": [
"Reviewer Expertise educational peer review",
"scholarly communication",
"research evaluation"
],
"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 opinion paper makes a well-argued case in favor of paying referees. The article acknowledges both the literature in support of and against the argument.\nMajor Comments:\nThe case is parsimoniously introduced in the section \"No more motivation to review for free\", where it states that \"monetary incentives might be one potential means to alleviate the burden on the peer review process to some extent\" and that \"paying professional reviewers can be implemented in conjunction with any of the solutions below\" (in Table 1). Table 1 is an interesting summary of various kinds of proposed solutions to improve peer review.\n\"Peer review cannot thrive in the current academic ecosystem\" is a fortunate name for the section before Conclusion. While I think it is enough for this paper, it only touches the tip of the iceberg. The literature on peer review is rich, but it is scarce in describing and explaining peer review as a functioning system. The current system appears to serve commercial publishers, who profit significantly from it, far better than it does authors, referees, and often under-compensated editors. The components, environment, and interconnections that underpin the system and drive its dynamics require further exploration. The Open Access movement has successfully promoted free readership, which seems good and logical given the public funding behind most research. However, it has not succeeded in reducing the costs exacerbated by the Serials Crisis, that motivated the movement.\nFurthermore, the peer review system has historically failed the research assessment culture by keeping reviews hidden from all but the editor, the author, and the referees (except for their own reviews). This has resulted in decades of systemic non-learning in paper assessment. The Open Science Movement now advocates for open reviews, a commendable initiative, though not always feasible for several reasons. The lack of shared reviews among referees over the decades remains a significant shortcoming. Making everything open is quite a radical change. This is clearly not a critique of this paper but highlights a broader systemic issue.\nRegarding potential hindrances to implementing reviewer payment, I suggest the author consider mentioning the fact that the proposed solution is hardly feasible for journals in Diamond Open Access - the ones that do not charge from author nor readers, mostly from poorer countries. They mostly rely on voluntary work, with some support from universities or government funding.\nMinor Comments:\nThe correct citation for item 18 (\"according to Waltman(2023)\") seems to be \"according to Waltman et al. (2023).\"\nSome editing might improve readability. For instance, in \"Those qualities, promoted by other schools of thoughts, are ...\", my understanding halted so I could think if the school of thought adopted also promotes those qualities and if the other schools of thought are the three other ones described by Waltman et al. (2023). It would be clear to me and the disturbance would not occur if the segment was written as \"Those qualities, also promoted by the other schools of thought, are ...\"\nThe article effectively uses the current literature, but I feel some statements lack a citation nonetheless. For instance, \"... increase in instances of fraud where for example false contact information of potential referees with non-institutional emails are suggested or when the peer review process has been manipulated\" could be backed by sources such as [1] or [2] (for instance).\nI think it would be appropriate to mention Publons (Table 1, p. 6) pointing out that it was bought by Clarivate and does not exist under that name, or, at least, to give a link (http://webofscience.help.clarivate.com/Content/publons.html). Future readers might be unable to find out what Publons was.\nIn Figure 1, the blue and green boxes are difficult to distinguish. They appeared identical to me - until I read the figure label.\nThere's are typos that I suppose either the author of the editorial team will correct, such as \"no through evaluation of the reviewed papers\" (\"thorough\") and \"Is the ultimate goal of academia to produce ... sometimes with questionable practices.\" (missing interrogation mark).\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
|
https://f1000research.com/articles/13-439
|
https://f1000research.com/articles/13-967/v1
|
27 Aug 24
|
{
"type": "Case Report",
"title": "Case Report: Sclerosing lymphocytic lobulitis of the breast: case report and literature review",
"authors": [
"Khaoula Magdoud",
"Sirine Bayar",
"Nejla Arifi",
"Sana Menjli",
"Rim Ben Hmid",
"Sirine Bayar",
"Nejla Arifi",
"Sana Menjli",
"Rim Ben Hmid"
],
"abstract": "Sclerosing lymphocytic lobulitis, also known as diabetic mastopathy, is a rare and benign pathology predominantly observed in young women with type I diabetes, typically with degenerative complications. Clinically, the lesion can mimic carcinoma. Biopsy remains the gold standard for a definitive diagnosis. Radical surgery is generally unnecessary when histological verification can be achievedusing core needle biopsy. This case report details the clinical and radiological findings, as well as the management of a 33-year-old patient with a 22-year history of type I diabetes who presented with sclerosing lymphocytic lobulitis.",
"keywords": [
"Sclerosing lymphocytic lobulitis",
"type I diabetes",
"complication",
"microbiopsy"
],
"content": "Introduction\n\nIt has long been believed that the mammary gland is not affected by degenerative complications of diabetes. This was thought to be true until 1984, when Soler and Khardorifirst described a case of mammary lesions associated with type I diabetes.1 Sclerosing lymphocytic lobulitis (SCLL) is a rare and benign tumor that accounts for less than 1% of all benign breast lesions.2 SCLL mostly occurs in women with type I diabetes at the stage of degenerative complications. However, cases of SCLL have also been described in patients with type II diabetes, autoimmune diseases such as Hashimoto’s thyroiditis, as well as in healthy individuals and in men.3 It sets a diagnostic trap since it mimics clinically a breast carcinoma.4 We present a case of SCLL occurring in a patient with type I diabetes for 22 years, detailing the associated clinical, radiological, and evolutionary aspects, along with the particularities of its management.\n\n\nCase report\n\nOur patient was a 33-year-old nulliparous woman without a family history of breast cancer, who presented with swelling in her right breast. She was diagnosed with type I diabetes 22 years ago and was administered a high insulin dose. Her diabetes was at the stage of degenerative complications, with hypertension for three years, managed with an angiotensin-converting enzyme inhibitor, and stage III retinopathy. The glycosylated hemoglobin level was 8.2%.\n\nThe patient was referred to us for consultation with a right-sided breast tumor. On inspection, asymmetry of the two breasts was noted, with an increased right breast size. On palpation, a 5 cm retroareolar tumor on the right side was identified, characterized by stony consistency and slight mobility with respect to the deeper layers, without signs of inflammation or palpable lymph nodes. No particular mention was made of the left breast.\n\nBreast ultrasound revealed a heterogeneous retroareolar hypoechoic formation on the right, measuring 5 × 3 cm, with irregular contours and attenuation of posterior echoes (Figure 1).\n\nIt revealed a right heterogeneous retroareolarhypoechoic, not well-limited formation of irregular contours of 5 × 3 cm in size with attenuation of the posterior echoes.\n\nA microbiopsy was performed, concluding that SCLL is a pathological finding with intralobular, periductal, and perivascular nodular lymphocyte infiltrations associated with marked lobular atrophy and extensive interlobular hyaline fibrosis (Figure 2).\n\n(HE X400): High-power photomicrograph of a hematoxylin and eosin-stained section of a breast biopsy specimen showingintralobular lymphocytic infiltration.\n\nGiven the poorly controlled diabetes, the risk of mutilating surgery (small overall breast volume) and high risk of recurrence, annual clinic, and radiological monitoring werechosen. The patient has been monitored regularly since 2019, and there has been no increase in tumor size or changes in the breast ultrasound findings.\n\n\nDiscussion\n\nSCLL or diabetic mastopathy are rare and benign pathological entity.1 The prevalence of this disease is unknown becauseof poor knowledge of the condition. The incidence of SCLLranges from 0.6% to 13%.1,5 According to Hunfeld and Bassler,6 SCLL accounts for less than 1% of all benign breast lesions. This percentage increased to 13% when considering only patients with type I diabetes.6\n\nThis condition mainly affects young women with type I diabetes, frequently at the stage of degenerative complications.7,8 Similar anatomical lesions have been less frequently described in other autoimmune pathologies (such as thyroiditis and lupus) and in patients with type II diabetes requiring insulin.3 The occurrence in men is exceptional; five cases have been reported in men.9,10\n\nSeveral physiopathological factors have been identified; notably, hyperglycemiaisbelieved to be responsible for abnormal accumulation and decreased connective tissue degradation in the extracellular matrix.11\n\n• The specific toxicity of exogenous insulin explains the appearance of this condition in type II diabetes after the use of insulin.12\n\n• An autoimmune process secondary to excess glycosylation in the extracellular matrix, thus forming neoantigens. This causesan autoimmune reaction against these neoantigens with lymphocytic infiltration, predominantly of B cells and macrophages. The presence of cytokines accentuatescollagenization.4,10–13\n\nClinically, SCLL typically presents as one or multiple unilateral or bilateral breast nodules with recent onset. These nodules had irregular contours, were hard or even stony in consistency, and were painless. They often grow rapidly and are mobile with respect to both superficial and deeper layers.3 It is frequently retroareolar and measures from 0.5 to 6cm in size.3 It was not associated with nipple discharge or inflammatory skin phenomena. Our patient presented with a stony retroareolar nodule that was poorly circumscribed, measured 5 cm, and suspected malignant.\n\nThese lesions clinically mimic those of breast cancer. Therefore, the use of complementary examinations or surgery is essential.\n\nMammography frequently shows overdensities, more or less regular opacities, and even dense breasts, but without architectural distortion or calcific foci.12–15 However, mammography remains difficult to interpret because of the young age of patients and the density ofbreast tissue.\n\nUltrasound, on the other hand, is more concerning, as the lesion often appears as a hypoechoic formation with irregular contours and strong ultrasound attenuation, which are characteristics frequently observed in polymitotic processes.15 Among the signs suggestive of malignancy, posterior acoustic shadowing and indistinct margins.16 Ultrasonographic abnormalities were observed in our patient.\n\nContrast-enhanced MRI may be indicativeof doubts regarding the diagnosis of malignant lesion.3 SCLL lesions present a homogeneously low enhancement with a gradual and progressive course and subsequent contrast wash-out seen on MRI imaging.17\n\nFine-needle aspiration is difficult to achieve becauseof the sclerotic nature of the lesion. Williams et al8 and Logan5 report an uninterpretable aspiration rate of 50% due to the poverty of cellular elements.\n\nBiopsy is therefore the examination of choice, which establishes the diagnosis.16Fine-needle biopsy is not recommended due to increased fibrosis. Coreneedle biopsy is the gold standard.14 Histological study revealed three types of elementary, non-specific associated lesions16: lymphocytic lobulitis: mononuclear inflammatory infiltration, more or less dense, associatedwithsmall B lymphocytes, plasma cells, and histiocytes. It is found mainly in the mammary lobulesand less markedly in the perivascular spaces and sometimes in the periductalspaces.\n\n• Fibrosis of intralobular connective tissue is always found, homogeneous, and dense.\n\n• Inconsistently, stromal epithelioid cells are homogeneously distributed.\n\nThere are two types of lymphocytic lobulitis (LL): SCLL and non-sclerosing LL (NSCLL).18 The two types of LL are distinguished by stromal features and a predominant population of B-cells in the former and T-cells in the latter.18\n\nImmunohistochemistry is only of interest to exclude the differential diagnosis of infiltrating lobular carcinoma (anti-keratin antibody) in cases where epithelioid cells are particularly numerous4,11\n\n• low-grade non-Hodgkin’s lymphomas when lymphoid infiltration appears suspicious.7\n\nConservative management can be considered when a histological diagnosis has been confirmed through a core-needle biopsy.2\n\nIn cases in which a conservative approach is chosen, it is crucial to educate the patient on proper breast self-examination techniques. A schedule for regular follow-up visits should be established, and an annual mammography is recommended.19\n\nFor cases involving a single lesion, surgical excision with an adequate margin of normal breast tissue remains the primary treatment option, particularly when no definitive histological diagnosis has been made, if the core biopsy findings are inconclusive, or if the patient has significant concerns regarding the breast lump.20\n\nA literature review indicated that 90% of the patients underwent excisional biopsy.2 The reasons cited included patient requests, anxiety, insufficient findings on fine-needle aspiration, the necessity to definitively rule out breast carcinoma, and clinician unfamiliarity with this condition.2\n\nWider margins during excision may help decrease the recurrence rate.21\n\nDespite treatment, a high recurrence rate (30–60% within 5 years) has been reported, with recurrences often affecting a wider region than the initial lesion.22 Bilateral and contralateral recurrences have also been documented.22 Most patients with recurrence undergo re-excision; however, this should be avoided in patients with a history of SCLL.2 In cases of multiple or recurrent lesions, once the diagnosis is established, subcutaneous mastectomy can be considered, especially for patients with multiple symptomatic lesions and small breasts, to avoid significant distortions from lumpectomy.23\n\nEach diagnosed case of SCLL should be individually managed. The type of surgery (mastectomy with immediate reconstruction or lumpectomy) should be carefully planned to ensure the best quality of life and optimal aesthetic outcomes.3 The surgical treatment plan should also consider the tumor and breast size, number of lesions, patient expectations, family history, and experience of the surgical team.3\n\n\nConclusion\n\nSCLL is a rare and benign disease associated with degenerative complications in women with type I diabetes. It is a diagnostic trap because it can clinically imitate breast carcinoma. Histological examination of the microbiopsies is sufficient to establish the diagnosis, thus avoiding mutilating surgery in these young diabetics.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and images was obtained from the patient on January 2024.\n\n\nAuthor’s contribution\n\nKhaoulaMagdoud: Conception, manuscript drafting, final approval.sirine Bayar: Conception, manuscript drafting, and final approval. Nejlaarifi: manuscript drafting andfinal approval. Sana Menjli: manuscript drafting andfinal approval. Rim Ben Hmid:conception, manuscript drafting, and final approval",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\nReporting guidelines\n\nThis work has been reported in line with the SCARE 2023 criteria. 24\n\nHarvard Dataverse: CARE checklist for “Sclerosing lymphocytic lobulitis of the breast: case report and literature review” doi.org/10.7910/DVN/50LCHP. 25\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\nSoler NG, Khardori R: Fibrous disease of the breast, thyroiditis, and cheiroarthropathy in type I diabetes mellitus. Lancet. 1984 Jan 28; 1(8370): 193–195. PubMed Abstract | Publisher Full Text\n\nAgochukwu NB, Wong L: Diabetic Mastopathy: A Systematic Review of Surgical Management of a Rare Breast Disease. Ann. Plast. Surg. 2017; 78: 471–475. Publisher Full Text\n\nGuzik P, Gęca T, Topolewski P, et al.: Diabetic Mastopathy Review of Diagnostic Methods and Therapeutic Options. Int. J. Environ. Res. Public Health. 2021 Dec31; 19(1): 448. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen XX, Shao SJ, Wan H: Diabetic mastopathy in an elderly woman misdiagnosed as breast cancer: A case report and review of the literature. World J. Clin. Cases. 2021 May 16; 9(14): 3458–3465. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLogan WW, Hoffman NY: Diabetic fibrous breast disease. Radiology. 1989 Sep; 172(3): 667–670. PubMed Abstract | Publisher Full Text\n\nHunfeld KP, Bässler R: Lymphocytic mastitis and fibrosis of the breast in long-standing insulin-dependent diabetics. A histopathologic study on diabetic mastopathy and report of ten cases. Gen. Diagn. Pathol. 1997 Jul; 143(1): 49–58. PubMed Abstract\n\nBouté V, Denoux Y, Feilel V, et al.: La mastopathie diabétique: complication peu commune du diabète de type I. J. Le Sein. 2003; 13: 261–269.\n\nWilliams PH, Rubin CM, Theaker JM: Sclerosing lymphocytic lobulitis of the breast. Clin. Radiol. 1995 Mar; 50(3): 165–167. PubMed Abstract | Publisher Full Text\n\nKudva YC, Reynolds CA, O’Brien T, et al.: Mastopathy and diabetes. Curr. Diab. Rep. 2003 Feb; 3(1): 56–59. PubMed Abstract | Publisher Full Text\n\nHadj AI, Ben Abdallah N, Kand K, et al.: Mastopathie fibreuse diabétique à propos d’un cas. Ann. Endocrinol. 2002; 63: 235–239.\n\nMurakami R, Kumita S, Yamaguchi K, et al.: Diabetic mastopathy mimicking breast cancer. Clin. Imaging. 2009 May-Jun; 33(3): 234–236. PubMed Abstract | Publisher Full Text\n\nSeidman JD, Schnaper LA, Phillips LE: Mastopathy in insulin-requiring diabetes mellitus. Hum. Pathol. 1994 Aug; 25(8): 819–824. PubMed Abstract | Publisher Full Text\n\nLammie GA, Bobrow LG, Staunton MD, et al.: Sclerosing lymphocytic lobulitis of the breast-evidence for an autoimmune pathogenesis. Histopathology. 1991 Jul; 19(1): 13–20. PubMed Abstract | Publisher Full Text\n\nAndrews-Tang D, Diamond AB, Rogers L, et al.: Diabetic Mastopathy: Adjunctive Use of Ultrasound and Utility of Core Biopsy in Diagnosis. Breast J. 2000 May; 6(3): 183–188. PubMed Abstract | Publisher Full Text\n\nLin W, Bao L: Mammography and Ultrasonography Manifestations of Sclerosing Lymphocytic Lobulitis of the Breast: A Series of Seven Case Reports. Curr Med Imaging. 2023 Sep 4; 20: 1–6. Epub ahead of print. Publisher Full Text PubMed Abstract |\n\nSato LT, de Mello GGN , Stiepcich MMA, et al.: Ultrasound as a Valuable Imaging Modality in Sclerosing Lymphocytic Lobulitis: Imaging Features Based on a Retrospective Cohort Analysis of 51 Cases. Can. Assoc. Radiol. J. 2021 Nov; 72(4): 767–774. PubMed Abstract | Publisher Full Text\n\nTuncbilek N, Karakas HM, Okten O: Diabetic fibrous mastopathy: Dynamic contrast-enhanced magnetic resonance imaging findings. Breast J. 2004; 10: 359–362. PubMed Abstract | Publisher Full Text\n\nNgo MH, Pinkus GS, Yeh ED, et al.: Non-sclerosing (T-cell) and sclerosing (B-cell) lymphocytic lobulitis in diagnostic breast biopsies: Clinical, imaging, and pathologic features. Hum. Pathol. 2024 Apr; 146: 28–34. PubMed Abstract | Publisher Full Text\n\nSankaye S, Kachewar S: Diabetic mastopathy. Australas Med J. 2012; 5(6): 296–299. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDavid G, Hicks MD, Susan C: Diagnostic Pathology, Breast. 2nd ed.Philadelphia, PA, USA: Elsevier; 2016; 530–531.\n\nBaratelli GM, Riva C: Diabetic fibrous mastopathy:sonographic-pathologic correlation. J. Clin. Ultrasound. 2005 Jan; 33(1): 34–37. PubMed Abstract | Publisher Full Text\n\nSalati SA, AlSulaim L: Diabetic mastopathy: A review of a breast carcinoma mimic. J Diabetology. 2024 Marc; 15(1): 4–11. Publisher Full Text\n\nPerret WL, Malara FA, Hill PA, et al.: Painful diabetic mastopathy as a reason for mastectomy. Breast J. 2006 Nov-Dec; 12(6): 559–562. PubMed Abstract | Publisher Full Text\n\nSohrabi C, Mathew G, Maria N, et al.: The SCARE 2023 guideline: updating consensus Surgical CAse REport (SCARE) guidelines. Int. J. Surg. 2023 May 1; 109(5): 1136–1140. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMagdoud K: Sclerosing lymphocytic lobulitis of the breast: case report and literature review. Harvard Dataverse. 2024; V1. Publisher Full Text"
}
|
[
{
"id": "329968",
"date": "02 Dec 2024",
"name": "Sweta Krishnan",
"expertise": [
"Reviewer Expertise Breast Imaging and Interventions"
],
"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, This is a nice case report illustrating a case of diabetic mastopathy, the clinical and imaging findings and the subsequent management. However, I suggest you go through my recommendations for changes in the manuscript and revise if needed. - Please correct the syntax errors present throughout the manuscript, especially in the case report and discussion parts. - Write “including men” instead of “and in men” in line 6 of the introduction as healthy individuals will include men as well. - Please mention explicitly if the patient had poor diabetic control and also detail the reasons for the same because you have mentioned that the patient was on high-dose insulin. - Please clarify what “No particular mention was made of the left breast” means. If the left breast was normal, please mention that it was normal. - For the imaging findings, please use the ACR BI-RADS 5th edition lexicon to describe the imaging findings used throughout the manuscript. I am putting the link here for your reference should you wish to go through it: https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/Bi-Rads\n- In Figure 1, the lesion appears to be oval-shaped with circumscribed margins. It is not possible to evaluate the shape and margins on one static image, however, I would suggest using a representative image as per the description used or changing the description of the mass as per the provided image. Comment about the vascularity within the lesion if the same was evaluated using Doppler, else you can ignore it. Please correct the size used in the description as per the image provided in Figure 1 because there is a large disparity of over 8mm.\n- Kindly clarify “Similar anatomical lesions have been less frequently described in other autoimmune pathologies (such as thyroiditis and lupus) and in patients with type II diabetes requiring insulin.” What is meant by “similar anatomical lesions”? Are the lesions the same clinically, on imaging, histologically, or a combination of these?\n- “The occurrence in men is exceptional; five cases have been reported in men.” I suggest an alternative way to frame this: The occurrence of the disease is very rare in men with only five cases reported in literature to date.\n- I suggest using the word “lump” instead of nodule to describe the lesion clinically. - The MRI part needs clarification. A lesion cannot show both a progressive enhancement and a wash out pattern. If both types of enhancement are seen in literature, please frame the sentence accordingly to avoid any confusion to the readers.\n- You have mentioned in detail the need for surgeries for different indications in a histologically diagnosed case of diabetic mastopathy. To my knowledge, surgeries are seldom performed in a biopsy-proven case of diabetic mastopathy. Please reiterate that routine clinical and imaging follow-up is the mainstay of management and surgeries are performed only for certain indications.\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? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-967
|
https://f1000research.com/articles/13-447/v1
|
03 May 24
|
{
"type": "Case Report",
"title": "Case Report: Methimazole-Induced Parotitis - An Unusual and Rare Presentation of Thyroid Storm",
"authors": [
"Ricky Rana",
"Emily Krier",
"Abubakar Tauseef",
"Jalal Dufani",
"Emily Krier",
"Abubakar Tauseef",
"Jalal Dufani"
],
"abstract": "A 56-year-old female with a medical history of unspecified hyperthyroidism and a recent thyroid storm presented to the ED with tachycardia, hypertension, and bilateral enlarged parotid glands. During a previous hospitalization, she was diagnosed with unspecified hyperthyroidism and started on methimazole. During hospitalization, laboratory findings suggested Graves’ disease with an acute thyroid storm. The patient also complained of enlarged parotid glands bilaterally. CT tomography of the neck revealed no calculi of the parotid glands but showed extensive fatty replacement, possibly related to methimazole use. Treatment with propranolol and IV hydrocortisone improved thyroid function. Due to the suspicion of methimazole-induced parotitis, she was transitioned to a reduced methimazole dosage for treatment of Graves’ disease, which subsequently improved her parotitis. Methimazole, the standard initial treatment for Graves’ disease, is generally well-tolerated. It can cause adverse reactions; however, parotitis is very rare and has been documented in only a few case reports. Owing to the limited number of reports, its incidence is currently unknown. Here, we present a case of methimazole-induced parotitis as an unusual presentation of thyroid storm. Drug-induced reactions can only be considered once common causes of parotitis such as viral infection, obstruction, and autoimmune diseases are ruled out. Treatment involves dosage adjustments and supportive care. Methimazole-induced parotitis is often misdiagnosed and overlooked because of the lack of reported cases. This necessitates future research into the reaction mechanisms and optimal treatment.",
"keywords": [
"methimazole",
"drug-induced reaction",
"parotitis",
"hyperthyroidsm"
],
"content": "Introduction\n\nParotitis, or inflammation of the parotid glands, is one of the most common disorders of the salivary glands and is generally caused by viral infections, obstruction of calculi, autoimmune diseases, and adverse effects of medications. The medications most associated with parotid gland enlargement include clozapine and phenylbutazone.1–3 Other drugs such as methimazole have been implicated in the development of parotitis; however, methimazole-induced acute parotitis is rare and easily misdiagnosed. Therefore, the incidence of methimazole-induced parotitis remains unknown. Based on limited experience, it generally resolves once the methimazole is stopped or the dose is decreased. Here, we present the case of a 56-year-old female who presented to the Emergency Department with thyroid storm and an incidental finding of methimazole-induced parotitis.\n\n\nCase presentation\n\nA 56-year-old female with a medical history of hypertension, gastroesophageal reflux disease, type 2 diabetes, unspecified hyperthyroidism, and recent thyroid storm was transferred from an outside hospital emergency department for the management of thyroid storm due to medication non-compliance. She had been hospitalized a few months prior for epigastric discomfort, nausea, tachycardia with a heart rate of 140 beats/min, and hypertension with a blood pressure of 175/80 mmHg. During that hospitalization, she was diagnosed with thyroid storm and was started on methimazole 10 mg twice a day and atenolol 50 mg daily which she took at home for 5 months. Patient was subsequently lost to follow up with endocrinology.\n\nDuring this hospitalization, the patient presented with recurrent symptoms of thyroid storm. Physical examination was unremarkable, except for a flushed and ill-appearing, disoriented female with bilateral, non-tender, enlarged parotid glands, and no sign of exophthalmos. A repeat laboratory investigation showed mild transaminitis, TSH level of 0.008 IU/ml with T3 of 594 ng/dl, free T4 of 6.79 ng/dl, thyroid peroxidase antibody over 1300 u/ml and an elevated TSH receptor antibody of 9.86 IU/L. The rest of the autoimmune and viral workup, including mumps serology, was unremarkable. The patient’s history, physical examination, and laboratory findings were consistent with Graves’ disease presenting with acute thyroid storm secondary to medication noncompliance. The patient presented with bilateral swelling at the level of the jaw. Ultrasound and CT scan of the neck showed no obstructing calculi in the parotid glands but showed extensive fatty replacement of both parotid glands with parotitis. Parotitis in this scenario could be due to the thyroid storm itself or to the use of methimazole.\n\nFor treatment of parotitis, the patient underwent conservative measures including warm compression, analgesia, and increased fluid intake. For the treatment of thyroid storm, she was started on propranolol 40 mg twice daily and methimazole 20 mg three times daily for 12 days. Her dose of propranolol was briefly increased to 60 mg every 6 hours for 2 days and 80 mg every 6 hours for 3 days before weaning back down. She was later transitioned to IV hydrocortisone 100 mg every eight hours and propylthiouracil 200 mg every 4 h per endocrinologist recommendation. Thyroid function gradually improved over 18 days of this treatment regimen. By hospital week 4, the patient was stable on 40 mg propranolol twice daily, propylthiouracil 100 mg twice daily, and maintained her dose of IV hydrocortisone 100 mg every eight hours for 7 days until her thyroid was surgically removed to prevent further complications. During her hospitalization, the patient was transitioned to propylthiouracil therapy for the management of Graves’ disease due to a high suspicion of methimazole-induced parotitis rather than parotitis induced by the thyroid storm itself. Her parotitis resolved with conservative treatment.\n\n\nCase discussion\n\nMethimazole is generally a well-tolerated treatment for Graves’ disease (GD). Among the patients who develop adverse drug reactions, 75% occur during the first 6 months of treatment.4 Common adverse effects include skin reactions, gastrointestinal upset, and agranulocytosis; however, they rarely manifest as pancreatitis or parotitis.3,5 While pancreatitis is a well-documented adverse effect of the drug, occurring with a risk ranging between 0.02% and 0.56%, parotitis is a much rarer side effect, with few reported cases.6 Based on a review of the literature and using the modified Naranjo probability scale for drug-induced parotitis, medications that met the criteria for establishing causality included l-asparaginase, clozapine, and phenylbutazone.1 Owing to the lack of reported cases of methimazole-induced parotitis, there is insufficient evidence to determine causality. In addition, owing to the paucity of reported cases, the incidence of methimazole-induced parotitis is currently unknown, and uncertainty surrounds the precise mechanism that drives this adverse reaction. Drug-induced hypersensitivity reactions, inflammation, and altered salivary gland function are some of the proposed hypotheses.2,7 With the symptoms appearing days or weeks after starting methimazole therapy, it seems more likely to be due to an idiosyncratic reaction rather than a dose-dependent reaction. It has been hypothesized that certain peptides are modified by methimazole and act as antigens that are then presented by specific HLA molecules in susceptible patients to trigger a cellular or humoral immune response.1,2 This explanation for an immune-mediated response is further strengthened by the fact that both pancreatitis and parotitis are known side effects. It has been shown that both glands share many histological and functional similarities.8 Furthermore, it is thought that a shared pancreatic and parotid peptide is involved in the development of a hypersensitivity reaction that can injure these glands.\n\nIn patients with parotitis, common causes such as calculi, viral infection, autoimmune diseases, and neoplastic processes should be ruled out before diagnosing medication-induced parotitis. Serological testing, including polymerase chain reaction, cytology, and imaging, is required to rule out these conditions.\n\nMethimazole-induced parotid gland inflammation can be managed by reducing the dosing of the offending drug, as observed in this case. Similar adverse reactions can be prevented by initially starting patients on a low dose of methimazole and gradually increasing the dosage over a few weeks to prevent adverse effects. If parotitis develops, the symptoms can be alleviated with supportive care, including fluids, warm compresses, and analgesics. If the patient does not respond to treatment, it is recommended to rule out other causes of parotid enlargement, including abscesses or bacterial infections. Methimazole is an efficacious treatment with a long-term remission rate for Graves’ disease after treatment, ranging between 30% and 70%.9\n\n\nConclusion\n\nMethimazole is the standard initial treatment for Graves’ disease and is generally well-tolerated in a wide variety of patients. It can cause some adverse reactions, most commonly skin rashes, and gastrointestinal upset; however, parotitis is a rarely reported adverse reaction documented in only a handful of case reports upon a review of the literature.\n\nOnce the common causes of parotid gland inflammation, such as viral infection, obstruction of calculi, and autoimmune disease, are ruled out, a drug-induced reaction can be considered. Treatment generally consists of stopping or decreasing the dose of the offending agent as well as supportive care such as fluids, warm compresses, and analgesics.\n\nOwing to the lack of reported cases, methimazole-induced acute parotitis is easily misdiagnosed and can be overlooked. Therefore, further research is needed to determine the precise mechanism causing this adverse drug reaction as well as the optimal treatment to prevent lasting damage.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details was obtained from the patient.",
"appendix": "Data availability\n\nNo data is associated with this article.\n\n\nReferences\n\nBrooks KG, Thompson DF: A review and assessment of drug-induced parotitis. Ann. Pharmacother. 2012; 46(12): 1688–1695. PubMed Abstract | Publisher Full Text\n\nThompson DF: Drug–induced parotitis. J. Clin. Pharm. Ther. 1993; 18(4): 255–258. PubMed Abstract | Publisher Full Text\n\nNaranjo CA, Busto U, Sellers EM, et al.: A method for estimating the probability of adverse drug reactions. Clin. Pharmacol. Ther. 1981; 30(2): 239–245. Publisher Full Text\n\nKarmisholt J, Andersen SL, Bulow-Pedersen I, et al.: Long-term methimazole therapy in graves’ hyperthyroidism and adverse reactions: A danish multicenter study. Eur. Thyroid J. 2022; 11(3). PubMed Abstract | Publisher Full Text | Free Full Text\n\nTaguchi M, Yokota M, Koyano H, et al.: Acute pancreatitis and parotitis induced by methimazole in a patient with graves' disease. Clin. Endocrinol. 1999; 51(5): 667–670. PubMed Abstract | Publisher Full Text\n\nYoshimura Y, Tatsushima K, Goshima Y, et al.: A case of methimazole-induced acute pancreatitis with an HLA allele causing antithyroid drug-induced agranulocytosis. J. Endocr. Soc. 2022; 6(5): bvac038. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoehlig RC: Parotid gland swelling due to methimazole. JAMA. 1969; 209(8): 1224. PubMed Abstract | Publisher Full Text\n\nSilvers AR, Som PM: Salivary glands. Radiol. Clin. North Am. 1998; 36(5): 941–966. Publisher Full Text\n\nMazza E, Carlini M, Flecchia D, et al.: Long-term follow-up of patients with hyperthyroidism due to graves’ disease treated with methimazole. comparison of usual treatment schedule with drug discontinuation vs continuous treatment with low methimazole doses: A retrospective study. J. Endocrinol. Investig. 2008; 31: 866–872. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "304171",
"date": "14 Aug 2024",
"name": "Lorenzo Scappaticcio",
"expertise": [
"Reviewer Expertise thyrotoxicosis and thyroid nodules and cancers."
],
"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 case is interesting, but not well-written. It needs the following things: - images (clinical and/or) of the enlarged parotid glands, showing how they decrease again. - the authors can not say which is the best mechanism under the enlargement of the parotids. Thus, they have to say in the discussion which are the main mechanisms, regardless of this case. - this case it can not be an example of idiosyncratic reaction, since the parotitis apparently disappeared after lowering the dose. -change the Title (since it is not clear if this happened after thyroid storm or methimazole). -in the discussion add some details and references regarding the possibility that severe thyrotoxicosis can induce parotitis.; -since you found only a found case reports, report: - where you found these cases (search strategy and online databases); -references of these case; - Table where you summaries the main findings of each case. -Table where you summarize the main findings of your case and your work. -cite the two relevant papers; (Scappaticcio et al.,2021)(Ref-1) (Scappaticcio et al.,2024)(Ref-2)\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? No\n\nIs the case presented with sufficient detail to be useful for other practitioners? No",
"responses": [
{
"c_id": "12261",
"date": "27 Aug 2024",
"name": "Ricky Rana",
"role": "Author Response",
"response": "Thank you for your valuable feedback and comments. I have tried to address the points you brought up in the updated version of the article."
}
]
}
] | 1
|
https://f1000research.com/articles/13-447
|
https://f1000research.com/articles/13-966/v1
|
27 Aug 24
|
{
"type": "Research Article",
"title": "Analysis of inbreeding depression in five S1 Cassava families of elite varieties at the seedling nursery and clonal evaluation trial stages.",
"authors": [
"Lydia Jiwuba",
"Alex Ogbonna",
"Ugochukwu Ikeogu",
"Favour Okeakpu",
"Kenneth Eluwa",
"Eunice Ekaette",
"Damian Njoku",
"Peter Okocha",
"Chiedozie Egesi",
"Emmanuel Okogbenin",
"Lydia Jiwuba",
"Alex Ogbonna",
"Ugochukwu Ikeogu",
"Favour Okeakpu",
"Kenneth Eluwa",
"Eunice Ekaette",
"Damian Njoku",
"Peter Okocha",
"Chiedozie Egesi"
],
"abstract": "Background Cassava is an outcrossing, highly heterozygous plant that is reported to suffer from inbreeding depression. However, unraveling recessive traits and exploring additive genes would require a limited level of inbreeding for the genetic improvement of cassava.\n\nMethod The impact of inbreeding depression (ID) on agronomic and biotic tolerance of cassava was evaluated using the S1 progenies of five African cassava varieties (TMS 30572, TME 419, TMS 98/0505, TMS 01/1371, and TMS 98/0002) at the seedling and clonal evaluation stages.\n\nResults At both trial stages, the effects of ID were severe on average performance of fresh root yield and fresh foliage yield; moderate on harvest index, dry matter content, vigor, and tolerance to cassava mosaic disease, cassava bacterial blight, and cassava anthracnose diseases; and less severe on plant height. Further examination of S1 families using molecular markers showed varying levels of heterozygosity at several loci across the genome. In addition, the degree of heterozygosity and ID varied by the S1 family. The TMS 01/1371 family showed the lowest degree of heterozygosity and ID on the average performance of different agronomic attributes, indicating that inbreeding may be strategically explored in this family to increase genetic gain and identify useful recessive traits. Lastly, the observed depression from inbreeding was higher in seedling evaluation than in clonal evaluation trials for fresh root yield, fresh foliage yield, harvest index, and dry matter content.\n\nConclusion S1 individuals showing relatively low heterozygosity based on SNP data were selected as parents to advance genetic gain in cassava. Generally, reduced heterozygosity was prominent in traits with severe ID impacts on average phenotypic performance. Our results highlight the relative importance of exploring non-additive genetic effects and transgressive segregations for favorable allele combinations in cassava improvement.",
"keywords": [
"Cassava",
"Seedling nursery stage",
"Clonal evaluation trial",
"Inbreeding depression",
"S1 progenies",
"Heterozygosity index",
"SNPs markers",
"Cassava improvement"
],
"content": "Introduction\n\nCassava (Manihot esculenta Crantz) plays a vital role as one of the primary sources of energy in the diets of most tropical countries. Additionally, its significance has grown, as it now serves as a crucial raw material for diverse industries. Consequently, understanding its genetics and factors influencing trait inheritance and expression is of utmost importance for its continued development.\n\nInbreeding occurs when two genetically related individuals mate, increasing the likelihood of their offspring having recessive or deleterious traits. This often results in a reduced fitness of a population, known as inbreeding depression. Cassava is highly heterozygous and typical cross-pollinated species, has been associated with severe inbreeding depression (Rojas et al., 2009). Nonetheless, it is encouraging to observe that interest in inbreeding is beginning to gain momentum (Ceballos et al., 2004, 2007; Rojas et al., 2009) in cassava improvement initiatives. Certainly, there is the potential to harness the benefits of inbreeding, similar to what has been achieved with maize, by capitalizing on both additive and non-additive effects (Rojas et al., 2009). Inbreeding will provide several advantages in cassava such as elimination of harmful recessive genes. Through selection, the less desirable genes are eliminated and superior genes are begin accumulated resulting in an increase in the productivity of the inbred populations (Ceballos et al., 2004). A key objective of this study was to explore the means of efficiently utilizing additive genetic variance in trait development through the fixation of beneficial alleles for key economic traits. By fixing useful alleles, we aimed to create valuable genetic stocks that can serve as parent lines, thereby reducing segregation issues that typically arise when evaluating F1 populations in breeding schemes for the development of improved varieties in Africa. This report presents the findings of our investigations for quantifying inbreeding depression in commercial elite African cassava lines. With these insights, we hope to pave the way for leveraging inbreeding as a strategic tool to enhance cassava breeding programs and to unlock its full potential as a vital crop for sustainable development.\n\n\nMethod\n\nThe field experiment was conducted at the National Root Crops Research Institute, (NRCRI) Umudike, Nigeria, while genotyping was conducted at the biotechnology laboratory of KBiosciences, Hoddesdon, London, United Kingdom. The NRCRI, Umudike, is located at latitude 5°30’N and longitude 7°30’E. It is at an altitude of approximately 122m above sea level and has an annual rainfall of approximately 2,166.3 mm, a temperature range of 22°C - 32°C, and a relative humidity range of 80–90%.\n\n\n\n• Seed production\n\nFive of the elite cassava genotypes (TMS 30572, TME 419, TMS 98/0505, TMS 01/1371 and TMS 98/0002) were obtained from the germplasm of International Institute of Tropical Agriculture, (IITA) Ibadan. These five elite cassava genotypes were used as progenitors (S0) to generate S1 progenies. They were not randomly selected because they were preferred for their wide adoption by farmers for favorable morphological and agronomic attributes in the elite germplasm. The elite genotypes were planted at a distance of 1 m × 1 m using 20 stem cuttings per genotype. For only self-pollination to occur, the plots were isolated by 100m apart from the neighbouring cassava plots. Self-pollination was performed for each elite clone. The pollinated flowers were secured within pollination bags in order to safeguard them from external pollen carried by bees. The bags were then carefully removed the following day. The mature fruits were harvested at 90 days after pollination, placed in a well-labelled pollination bags, and are allowed to dehiscent.\n\n• Establishment of the seedling evaluation trial\n\nHarvested S1 botanical seeds were allowed a two - month dormancy period before being sowed in nurseries in a screen house. The seeds were sown in trays filled with sterilized soil with a mixture of loamy and sandy soil at a ratio of 2:1 in the screen house. Seeds germinated quickly under optimal soil temperatures (30°C–35°C) and moisture regimes. They were irrigated twice daily, in the morning and evening. The seeds started germinating 10 to 12 days after planting and were transplanted when they attained a height of 15–20 cm. After two months in the nursery, S1 seedlings were transplanted to a well-prepared field where they were grown and evaluated. Harvesting was performed 12 months after planting, after which they were cloned to generate at least 10 stem cuttings per seedling for clonal evaluation.\n\n• Establishment of the clonal evaluation trial\n\nIn the clonal evaluation trial, ten cuttings of each S1 genotype were planted in the field for evaluation. All progenies belonging to the same family, together with the parents, were established in the same block in an augmented (Federer, 1956) experimental design. In this design, each clone or genotype was planted in a row and are not replicated while the parents serve as checks and are replicated in each block. The spacing within rows was 1 m, and the row spacing was 1.5 m to minimize inter-plot interference.\n\nGenomic DNA was extracted from the leaf samples of each individual of the S1 population (from five families) and from the parents, as described by Dellarporta et al. (1983). A total of 200 SNPs markers with good genome distribution and coverage were analyzed in 260 DNA samples. Constituent reagent volumes for the KBioscience Competitive Allele-specific PCR genotyping system (KASP) genotyping mix were as follows:\n\n• 5 μl DNA\n\n• 5 μl KASP 2X reaction mix\n\n• 12 μl of Allele-specific primer 1 (100 μM)\n\n• 12 μl of Allele-specific primer 2 (100 μM)\n\n• 30 μl of common (reverse) Primer (100 μM)\n\n• 46 μl of H2O/Tris-HCl (10 mM, pH 8.3)\n\nProcedure\n\n5 μl DNA samples were arrayed on a PCR plate. The DNA was genotyped as a liquid sample. The KASP genotyping mix was dispensed robotically into PCR plates containing 5 μl DNA samples and briefly vortexed. The plate was sealed with an optically clear seal and thermally cycled using a Peltier block-based thermocycler at 94°C for 15 minutes. The plate was read using a suitable fluorescent plate reader at ambient temperature. Genotyping data were analyzed using the most FRET-capable plate readers.\n\n\n\n• Pests and diseases measurement\n\nDuring the growth period of the seedling nursery and clonal trials, the plants were evaluated for Cassava Mosaic Disease (CMD), cassava bacterial light (CBB), Cassava Anthracnose Disease (CAD), and vigor 1, 3, 6, 9, and 12 Months After Planting (MAP).\n\nA. Vigor was evaluated based on a scale of 1-5; where 1 = very weak (plants somewhat stunted with very thin stems), 2 = weak (thin stem), 3 = intermediate (moderately growing), 4 = vigorous (fast growing and no bending), and 5 = extra vigorous (very fast growing, strong, and no bending) (IITA, 1990).\n\nB. Cassava Mosaic Disease (CMD) was visually scored on a scale of 1-5; where 1 = no symptoms observed; 2 = mild chlorotic pattern on the entire leaflet; 3 = strong mosaic pattern on the entire leaf; 4 = severe mosaic/distortion of 2/3 of leaflet; and 5 = severe mosaic/distortion of 4/5 of leaflet.\n\nC. Cassava Bacterial Blight (CBB) was visually scored on a scale of 1-5; where 1 = no symptoms observed; 2 = only angular leaf spots; 3 = exclusive leaf blight, leaf wilt and defoliation, and gum exudation on the stem; 4 = exclusive leaf blight, defoliation, and die-back; and 5 = complete defoliation and stem die-back.\n\nD. Cassava Anthracnose Disease (CAD) was visually characterized. A scale of 1 to 5 was used to rate symptoms: 1 = no symptoms observed; 2 = few shallow cankers on woody stems; 3 = many deep cankers on woody stems; 4 = many oval lesions on green stems; and 5 = many lesions on green stems and severe necrosis at leaf axils.\n\n• Morphological and Agronomic traits evaluation\n\nAt harvest for seedling and clonal evaluation trials at 12 MAP, plant height (cm) was measured from the soil level to the highest apical point of the plant at harvest. Phenotypic assessments were performed on eight innermost plants per clone. Roots were separated from the vegetative harvestable biomass (leaves, stems, and the original planting stake) and independently weighed using a weighing balance. The fresh root yield and fresh foliage yield (kg plant−1) were calculated. The harvest index (root biomass as a proportion of total biomass) was computed for each clone following the procedure outlined by Kawano (1990). Estimation of Dry Matter Content (DMC) (measured as a percentage) in the root samples was determined using the specific gravity method, as suggested by Kawano et al. (1987). The procedure included weighing of three (3) kg of roots with a weighing balance and then placing them in a nylon bag. The bag with roots was hung on a hanging balance of 6 kg capacity while suspending the bag in a tank with water, ensuring that the bag did not touch the bottom and that the roots were completely underwater. The weight of the water was then determined.(IITA, 1990)\n\nThe number of progenies assessed differed across the families, making the dataset largely uneven. Summary statistics (average, range, variance, and skewness) for all traits were calculated for each family. The dataset for all the traits was subjected to a paired sample t-test using R. Inbreeding depression was estimated for plant height, vigor, fresh root yield, fresh foliage yield, harvest index, dry matter content, and disease data; cassava mosaic disease, cassava bacterial blight, and cassava anthracnose disease as a percentage of the S1 average. ID was obtained based on the equation reported by Rojas et al. (2009):\n\nInbreeding depression was assessed at the family level. The lower the ID value, the more severe the level of depression, indicating that the performance of the S1 progenies is relatively close to that of the S0 progenitor compared to the ID values that have higher depression.\n\nThe heterozygosity index was obtained using the following equation suggested by Scotti et al. (2000):\n\nWhere Sn is the inbreeding generation in which the effect was calculated, Sn-x is the generation taken as a reference (the parental S0), and H is the mean of heterozygosity loci. Data were analyzed using GenStat version 12.1 edition (2009).\n\n\nResults\n\nTable 1 presents the origin of the elite clones and the sizes of their respective S1 families, which were evaluated in both seedling nursery and clonal evaluation trials. The selection of these families (TME 419, TMS 01/1371, TMS 30572, TMS 98/0002 and TMS 98/0505) for evaluation was based on the commercial significance of their progenitors in Africa. Specifically, family TME 419 started with 51 seeds, of which 33 genotypes were evaluated in seedling nurseries and 23 were evaluated in clonal evaluation trials. Similarly, for family TMS 01/1371, 79 seeds were produced, 63 were evaluated in the seedling nursery stage, and 35 were evaluated in the clonal stage. In the case of family TMS 30572, out of 111 seeds produced, 90 genotypes survived the seedling stage, and after the usual losses in the cloning process, 51 clones were evaluated in the clonal stage. For family TMS 98/0002, 44 out of the initial 64 seeds were evaluated in the seedling nursery and 24 in the clonal stage. Lastly, family TMS 98/0505 began with 68 seeds, but only 25 cloned genotypes were evaluated at the seedling stage, and only 14 cloned genotypes were evaluated at the clonal stage. These losses are typical and are also observed in the evaluation of the full-vigor germplasm. Despite these losses, the samples of S1 genotypes representing the partially inbred populations were considered unbiased representations of all progenies that could be obtained from the self-pollination of the respective progenitors. This selection process ensures a fair representation of the evaluated progenies and allows for a comprehensive assessment of the performance and potential of partially inbred populations in breeding programs.\n\nInbreeding depression (ID) is generally lower for pests and diseases than for complex traits such as yield. Inbreeding depression as a percentage of the performance from the S0 generation measured in five S1 families based on disease severity in seedling and clonal evaluation trials are presented in Tables 2 and 3, respectively. The disease data had negligible additive effects and had low ID values.\n\nIn the seedling evaluation trial, CMD had the lowest average ID value (-94.30%), which ranged from -141.00% (TME 419) to 0.50% (TMS 30572), followed by CBB with an average ID value of -71.90% and with a range from -175.00% (TMS 98/0002) to 7.00% (TMS 30572), followed by CAD with an average ID value of -46.80%, ranging from -117.00% (TMS 98/0505) to 23.00% (TMS 30572) (Table 2). In the clonal evaluation trial, CMD had the lowest average ID value (-41.08%), ranging from -57.80% (TMS 30572) to -16.57% (TMS 01/1371), followed by CAD with an average ID value of -33.44% and ranging from -54.90% (TMS 30572), followed by CBB with an average ID value of -21.66%, ranging from -46.83% (TMS 98/0505) to 9.14% (TMS 01/1371) (Table 3).\n\nPhenotypic assessment of the families revealed some superior S1 clones, which were found to substantially outperform their S0 progenitors. In the case of cassava mosaic disease, cassava bacterial blight, and cassava anthracnose disease, no significant depression was observed (Tables 2 and 3).\n\nAgronomic traits revealed notable ID, with fresh root yield exhibiting the highest ID values at 86.55% and 53.05% at the seedling nursery and clonal evaluation stages, respectively (Tables 4 and 5). Other agronomic traits, such as fresh foliage yield and harvest index, also displayed considerable ID values (38% and 22%, respectively) at the clonal evaluation stage (Table 5). The effects of ID tended to be relatively higher for more complex traits given their polygenic character. Reduced heterozygosity associated with selfing (S1) had a significant impact on fresh root yield and foliage, underscoring the relative importance of non-additive genetic effects in their inheritance. Some transgressive segregants were observed in the S1.\n\nAs with pests and diseases, ID was lower than that of the complex traits. The average ID for vigour in the seedling evaluation trial was 20.83% ranging from -3.03% in family TMS 01/1371 to 44.44% in family TMS 30572 (Table 4) while in clonal evaluation trial, the average ID value for vigour was 28.22% ranging from 1.71% in family TMS 01/1371 to 46.47% in family TMS 30572 (Table 5). For plant height, the average ID observed at the seedling nursery and clonal evaluation stages were -25.49% and -6.50%, respectively, and all families produced S1 genotypes with plant heights superior to those of their S0 progenitor genotypes in both stages. This demonstrated that the performance of the progenies was relatively close to that of the S0 progenitors. Based on these results, this set of traits appears to be less sensitive to inbreeding depression.\n\nA paired (dependent) sample t-test was used to compare the means of the seedling nursery and clonal evaluation stages to determine whether there was a statistically significant difference between these means. The results revealed a significant difference between the seedling nursery and clonal evaluation stages for all traits evaluated (Table 6). There was a significant difference in the CMD scores for the seedling nursery (M = 1.56, SD = 0.62) and clonal evaluation trials (M = 2.05, SD = 0.79); t (146) = 5.74, p = 0.000. For CBB, the clonal evaluation trial showed a significantly higher level of resistance (M = 2.44, SD = 0.39) than the seedling nursery stage (M = 3.01, SD = 0.70), t (146) = 8.25, p = 0.000. Similarly, the mean score for CAD at the clonal evaluation stage (M = 1.54, SD = 0.2) showed a higher level of resistance than the mean score at the seedling nursery stage (M = 2.26, SD = 0.54); t (146) = 15.72, p = 0.000.\n\nMore vigorous plants were observed at the clonal evaluation stage (M = 3.23, SD = 0.64) than at the seedling nursery stage (M = 2.52, SD = 0.95; t (146) = 7.92, p = 0.000). There was a significant difference between the heights of plants at the seedling nursery (M = 174.22, SD = 50.16) and clonal evaluation stages (M = 204.44, SD = 57.06); t (146) = -4.87, p = 0.000.\n\nThere was a significant improvement in fresh foliage yield from the seedling nursery stage (M = 1.44, SD = 1.81) to the clonal evaluation stage (M = 5.17, SD = 5.03); t (146) = -8.42, p = 0.000. The result also showed that fresh root yield was significantly higher at the clonal evaluation stage (M = 17.28, SD = 13.22) than at the seedling nursery stage (M = 1.53, SD = 1.78); t (146) = -3.72, p = 0.000. The dependent sample t-test showed that the seedling nursery stage (M = 0.49, SD = 0.19) had a lower mean harvest index value than the clonal evaluation stage (M = 0.57, SD = 0.15), t (146) = -14.17, p = 0.000. The clonal evaluation trial showed significantly lower root dry matter content (M = 27.54, SD = 5.24) than the seedling nursery stage (M = 29.89, SD = 6.75); t (146) = 3.48, p = 0.001.\n\nUsing SNPs molecular markers for heterozygosity, the S1 generation showed a good proportion of heterozygotes at several loci across the genome, indicating that heterozygosity is very high in cassava, and several selfing cycles may be required to reduce it drastically. The heterozygosity indices of S1 progenies are shown in Figure 1. SNP analysis revealed percentage heterozygosity between 12% and 65% in the population. The average heterozygosity reported for the S1 families is shown in Table 7. The results showed that estimates of the heterozygosity index tended to increase and improve as a greater number of SNP markers were used. This suggests that an optimum number of SNPs should be determined to improve the precision of heterozygosity estimates in cassava. Figure 2 shows the distribution of S1 progenies based on their percentage heterozygosity estimated using SNP markers. The findings also demonstrated that a majority of the progenies, specifically over 55%, exhibited heterozygosity values below 25%. This suggests that there are quality materials to pass on to the next inbreeding generation, which will likely result in less heterozygosity in the subsequent breeding generation.\n\n\nDiscussion\n\nPhenotypic measurements of key breeding traits were performed during the seedling and clonal evaluation trials. This study explored SNP markers to assess the heterozygosity of the top five elite clones that have been extensively used as parents in cassava breeding programs.\n\nThe inbreeding depression for fresh root yield, which is a very complex trait (involving many genes), was found to be higher than the values obtained for other traits evaluated in this study. These results suggest that a high ID was more likely for traits that were more quantitatively controlled (e.g., root yield) than traits controlled by fewer genes, for example, plant height. This agrees with the findings of Castro et al. (2006).\n\nIn the case of cassava mosaic disease, cassava bacterial blight, and cassava anthracnose disease, little depression was observed. This was probably because of additive genetic effects, in addition to the fact that pests and disease resistance are often affected by a few genes (including dominant or major gene effects). For example, previous molecular studies indicated that CMD resistance in two of the varieties, TMS98/0505 and TMS98/0002, used as parents, is mainly controlled by a single dominant gene resistance (Okogbenin et al., 2013).\n\nThese results suggest that breeders can explore inbreeding for these traits in the early stages of the selfing cycle within the breeding scheme, potentially enhancing their genetic progress. Some previous studies in cassava have reported disease resistance to CMD and CBB as being quantitatively controlled, with some being recessive. Furthermore, the low ID for pests and diseases shows that traits that are strongly influenced by additive genetic variance stand to benefit most, leading to genetic gain. Additionally, useful beneficial recessive traits can be effectively explored while simultaneously selecting undesirable recessive traits.\n\nIn general, the inbreeding depression values were higher in the seedling evaluation trial than in the clonal evaluation trial for fresh root yield, fresh foliage yield, harvest index, and dry matter content. The use of seeds versus stem cuttings may have influenced the results. In the seedling trial, cassava was raised from seeds, whereas stem cuttings were used as planting materials in the clonal trial. Seeds typically produce plants with fewer and smaller roots than those raised from stem cuttings (clonal stage) (FAO, 1977). Food reserves in stem cuttings aid in rapid establishment and improved performance. Therefore, it is important to explore later generations to evaluate inbreeding depression for these traits.\n\nA paired samples t-test was performed to determine whether there was a statistically significant difference between seedling nursery and clonal evaluation stages for all traits evaluated. The results revealed a significant difference between the seedling nursery and clonal evaluation stages for all traits evaluated. The expression of the disease traits (cassava mosaic disease, cassava bacterial blight, and cassava anthracnose disease) was more severe at the seedling nursery stage than at the clonal evaluation stage. Likewise, morphological traits (vigor and plant height) performed better at the clonal evaluation stage than at the seedling stage. This could be because during the process of moving from the seedling evaluation stage to the clonal evaluation stage, genotypes with poor vigor were eliminated, while vigorous genotypes were selected for further testing. For yield traits, such as fresh foliage yield, fresh root yield, and harvest index, the use of stem cuttings may have provided better results in the clonal evaluation stage. The dry matter content was significantly lower at the clonal evaluation stage than at the seedling nursery stage. At the seedling nursery stage, the genotypes mainly had fibrous roots and a higher dry matter content than at the clonal evaluation, where tuberous roots and a lower dry matter content were observed.\n\nCassava has been demonstrated to be a highly heterozygous species (Kawano et al., 1978; Pujol et al., 2005). Inbreeding depression, such as that observed in this study, was therefore expected. ID is the result of a reduction in heterozygosity levels in loci with dominant gene effects and because of the increased frequency of expression of unfavorable alleles (Falconer, 1981; Miranda-Filho, 1999, Vencovsky and Barriga, 1992). Inbred lines are more suitable for breeding and genetic research due to their lack of dominance effect and reduced genetic load (undesirable alleles), making them superior parents.\n\nFive S1 individuals, one genotype each from the families of TMS 98/0505, TME 419, and TMS 30572 and two genotypes from the family of TMS 01/1371 showing relatively low heterozygosity based on SNP data, were selected as parents for further selfing to assess ID. Therefore, these genotypes were further advanced to generate an S2 population for further study.\n\n\nConclusion\n\nThe impact of inbreeding on pests, diseases, and morphological and architectural traits in the S1 generation was non-severe. Notably, the presence of transgressive segregants in the population for key strategic traits of the crop is indicative of favorable allele combinations at the S1 stage. Therefore, the results demonstrate that inbreeding can be strategically explored in breeding for these traits to increase genetic gain and possibly identify recessive traits. At the early stages of the cassava breeding scheme, most key traits, including disease resistance, were not severely affected at S1. This presents an opportunity to identify major or a few genes associated with disease resistance and to fix them in early generations to generate valuable parent stocks. These parent stocks can then be used in crosses, enabling the exploration of both additive and non-additive variances for polygenic traits in later breeding cycles. Moreover, the strategic use of inbreeding allows for early selection of productivity traits once genetic stocks become available. This can significantly shorten the breeding cycle, especially when appropriate technologies are employed to rapidly multiply selected genotypes in larger yield trials. In summary, our findings suggest that inbreeding can be a valuable tool in cassava breeding for specific traits, offering potential benefits in accelerating genetic progress and identifying essential recessive traits. By incorporating inbreeding strategies and leveraging advanced technologies, cassava breeding programs can make significant strides in developing improved varieties that address the challenges of pests, diseases, and productivity in this vital crop.",
"appendix": "Data availability statement\n\nThe datasets presented in this study can be found in the figshare repository.\n\n1. SNPs estimates for heterozygosity , DOIs: https://doi.org/10.6084/m9.figshare.26312278.v1 (Jiwuba, 2024b)\n\nThis project contains the following underlying data:\n\n• S1 SNPS.xlsx\n\n2. Inbreeding depression seedling and clonal evaluation trials.xlsx, Doi: https://doi.org/10.6084/m9.figshare.26317900 (Jiwuba, 2024a)\n\nThis project contains the following underlying data:\n\n• inbreeding depression seedling and clonal evaluation trials.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nSpecial thanks to the technical team working at NRCRI, Umudike, for their assistance during the field activities and data collection.\n\n\nReferences\n\nCastro AM, Perez JP, Fregene M, et al.: Use of Molecular markers to estimate level of heterozygosity in selfed lines of Cassava (Manihot esculenta Crantz) . Project IP3, Improved cassava for the developing world. CIAT Annual report 2006. Cali, Colombia: Centro internacional de Agricultura Tropical (CIAT); 2006.\n\nCeballos H, Iglesias CA, Perez JC, et al.: Cassava breeding: Opportunities and challenges. Plant Mol. Biol. 2004; 56: pp. 503–516.\n\nCeballos H, Fregene M, Perez JC, et al.: Cassava genetic improvement. Breeding major food staples. 2007; 965–991.\n\nDellarporta SL, Wood J, Hicks JR: A plant DNA minipreparation: version II. Plant Mol. Biol. Report. 1983; 1: 19–21.\n\nFalconer DS: Introduction to Quantitative Genetics. 2nd ed.New York, USA: Longman; 1981; p. 400.\n\nFAO: Cassava Processing. Document prepared by M.R. Grace. FAO Plant Production and Protection Series No.3.1977.\n\nFederer WT: Augmented (or hoonuiaku) designs. Hawaiian Planters’ Record LV. 1956; 2: 191–208.\n\nGenStat: GenStat for Windows. 12th ed.Hemel Hempstead, UK: VSN International; 2009. Web page: GenStat.co.uk.\n\nIITA: Cassava in tropical Africa. A reference manual. Ibadan, Nigeria: International Institute of Tropical Agriculture; 1990.\n\nJiwuba L: inbreeding depression seedling and clonal evaluation trials.xlsx (Version 1). figshare. 2024a. Publisher Full Text\n\nJiwuba L: S1 SNPS.xlsx (Version 1). figshare. 2024b. Publisher Full Text\n\nKawano K, Amaya A, Daza P, et al.: Factors affecting efficiency of hybridization and selection in cassava (Manihot esculenta Crantz). Crop Sci. 1978; 18: 373–376.\n\nKawano K: Harvest index and evolution of major food crops cultivars in the tropics. Euphytica. 1990; 46: 195–202.\n\nKawano K, Gonçalves FW, Fukuda M, et al.: Genetics and environmental effects on dry matter content of cassava roots. Crop Sci. 1987; 27: 69–74.\n\nMiranda-Filho JB: Inbreeding depression and heterosis. The genetic exploitation of heterosis in crops. Coors JG, Pandey S, editors. Madison WI: ASA; 1999; pp. 69–81.\n\nOkogbenin E, Moreno I, Tomkins J, et al.: Marker-assisted breeding for cassava mosaic disease resistance. Translational genomics for crop breeding: biotic stress. 2013; 1: 291–325.\n\nPujol BP, David P, McKey D: Microevolution in agricultural environments: How a traditional Amerindian farming practice favours heterozygosity in cassava (Manihot esculenta Crantz, Euphorbiaceae). Ecol. Lett. 2005; 8: 138–147.\n\nRojas MC, Perez JC, Cellabos H, et al.: Analysis of inbreeding depression in eight S1cassava families. Crop Sci. 2009; 49: 543–548.\n\nScotti C, Pupilli F, Salvi S, et al.: Variation in vigor and in RFLP-estimated heterozygosity by selfing tetraploid alfalfa: new perspectives for the use of selfing in alfalfa breeding. Theor. Appl. Genetics. 2000; 101: 120–125.\n\nVencovsky R, Barriga P: Genética Biométrica no Fitomelhoramento. Ribeirão Preto, Brazil: Sociedade Brasileira de Genética; 1992; p. 486."
}
|
[
{
"id": "327456",
"date": "17 Oct 2024",
"name": "Charles Orek",
"expertise": [
"Reviewer Expertise Application of biotechnological tools for biotic and abiotic stress resistance in cassava and other root crops"
],
"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\nExploitation of inbreeding for improved cassava performance is an exciting but relatively unexplored field of research. This study is thus foundational. My brief comments on each section that the authors can improved is as below:\n\n1) Introduction / background is extremely brief. The authors can add more information for proper justification of the study.\n\n2) Seed production in cassava takes a long time. The authors can indicate how long it took for the seeds to mature post-pollination\n\n3) Some references are very old (e.g. Federer, 1956; Dellarporta et al. 1983; Kawano et al. 1987; IITA, 1990; Kawano, 1990; Scotti et al. 2000, FAO, 1977 among others. The authors can replace these with more recent references to indicate that they are up to date with recent development in this particular field of research. Unless no recent research has been previously done...…..then the old references can make sense. 4) The authors have not indicated references for the Pests and Diseases measurements. For examples references for the methods the authors adopted in scoring of CMD, CBB and CAD are lacking. The sources of these methods should be added. Unless the authors are the ones who came up with the scoring methods. 5) \"This agrees with the findings of Castro et al. (2006)\". Perhaps the authors can indicate / report a one-sentence summary of the actual findings from Castro at al. 2006.\n\n6) \"Some previous studies in cassava have reported disease resistance to CMD and CBB as being quantitatively controlled, with some being recessive\". The authors can provide references for these studies for ease of confirmation of this point in the discussion.\nNB: This is a good research initiative and more should be done in exploitation inbreeding for better cassava performance.\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/13-966
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https://f1000research.com/articles/12-1165/v1
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18 Sep 23
|
{
"type": "Research Article",
"title": "Clinical use of autologous cell-based therapies in an evolving regulatory landscape: A survey of patient experiences and perceptions",
"authors": [
"Ubaka Ogbogu",
"Nevicia Case",
"Nevicia Case"
],
"abstract": "Background: Clinical treatments involving autologous cell-based therapies (ACBT) remain prevalent despite a lack of scientific backing and an evolving regulatory landscape aimed at assessing their safety and efficacy for clinical adoption. This study seeks to assess patients’ experiences and perceptions of clinical treatments involving ACBT and their knowledge and views of the regulatory context and associated governance issues. Methods: An anonymous online survey of 181 participants who have been treated or are in the process of being treated with ACBT. Recruitment was via social media platforms. Data was collected through Qualtrics and analyzed using SPSS 29 for the quantitative responses and NVivo 1.7.1 for the qualitative responses.\n\nResults: Several themes emerged from the data, including the prominent role of healthcare providers throughout the patient journey, informational practices during the clinical encounter, the high prevalence of pay-for-participation trials, patients’ gaps in regulatory knowledge, and patients’ priorities regarding clinical trials and regulation of ACBT. Conclusions: The study makes a novel contribution to the literature by providing the first analysis of patients’ experiences and perceptions of an emerging cell-based therapy within an evolving regulatory landscape. The findings serve as a valuable resource for developing policy, promoting scientific rigor, and ensuring ethical oversight of ACBT and other upcoming cell-based therapies.",
"keywords": [
"autologous cell-based therapy",
"cell therapy",
"stem cells",
"advanced therapies",
"regenerative medicines",
"health product regulation",
"patient experience",
"patient education",
"stem cell regulation",
"clinical trial ethics",
"pay-to-participate trials",
"healthcare providers"
],
"content": "Introduction\n\nIt has been widely reported in the literature and news media that individuals are seeking and obtaining putative cell-based therapies in advance of regulatory approvals and, in many instances, prior to the availability of any or high-quality evidence1,2 supporting their safety, effectiveness and/or clinical adoption.3 The first study of this phenomenon, published in 2005, described stem cell-based therapies with little or no evidentiary support offered mainly via online marketing to patients who were willing to travel internationally to receive them.4 Since then, the phenomenon has evolved into a national and international industry in many jurisdictions, including in countries with highly developed health products regulatory systems, such as Canada, Australia, the European Union, and the United States (U.S.).5–7 Studies have tracked the proliferation of treatment providers in countries around the world serving local and international clientele,8 using a variety of strategies to reach potential clients,9 and offering a variety of interventions that are often neither approved by regulators, nor backed by high quality evidence.10 Studies have also reported on the adverse events associated with these interventions,11 the experiences of patients who access the treatments, and their reasons for doing so,11,12 provider perspectives,13 and the evolution of and trends in the industry.14\n\nThe phenomenon has attracted regulatory, legal, ethical and media scrutiny and responses, including sanction by regulators,15 court challenges,16 legislative and policy reform,17 and policy recommendations addressing associated issues and challenges, such as the role of consumer protection and truthful advertising in addressing false therapeutic claims,18 and healthcare professional involvement and ethics.19 Some jurisdictions have established or are in the process of establishing legal and regulatory changes designed to clarify and strengthen the framework for regulatory review and marketing authorization of regenerative medicines, which include cell-based therapies.15,19,20 These changes respond, in part, to legitimate questions about how to classify and assess these therapies, many of which are innovative and present differently from conventional pharmaceuticals.21 Regulatory difficulties also arise from claims, usually made by treatment providers that certain cell-based therapies are not within regulatory scope because they are not health products per se, but, rather, are simply medical procedures that utilize cells or cell-based products.22–24\n\nThe latter claim is most evident in the regulatory debate surrounding the use of human-derived autologous cells in medical procedures, which is often referred to as “autologous cell-based therapy” (ACBT). Generally, ACBT “involves the removal, some level of manipulation or processing, and re-introduction of a person’s own cells to treat or prevent a disease, disorder or medical condition.”25 There is mounting evidence of providers applying ACBT for the clinical management of a variety of medical conditions, and especially for osteoarthritis, musculoskeletal disorders, and sports injuries.26 Jurisdictions such as the U.S., the European Union, Canada and Australia have sought to clarify whether and what cells used in ACBT constitute regulated health products.27 While the details as to what constitutes a regulated “ACBT product” (i.e., cell or cell-derived material used in ACBT) varies by jurisdiction, some commonalities exist. Generally, some ACBT products are exempt from health product regulation (under certain conditions), while others require full pre-marketing approval under an appropriate regulatory pathway.17,28,29 The differences between both categories depends largely on risk classification and in some cases, on whether and to what extent the cells have been manipulated prior to clinical administration.16,30,31\n\nHowever, this increased clarity appears not to have prevented the use of regulated but unapproved and/or unauthorized ACBT products in medical procedures, and there is evidence that patients continue to access such products.31–33 As part of efforts to achieve regulatory compliance, some regulators, such as Health Canada and the Australian Therapeutic Goods Administration, have required treatment providers to conduct clinical trials to obtain evidence to support clinical deployment of various ACBT products.17,34,35 This requirement has led to a proliferation of “pay-to-participate” or “pay-to-play” clinical trials, whereby patients seeking ACBT are asked to pay to participate in the trials.36,37 There is also speculation that patients who have paid for what they think is a medical procedure are unwittingly enrolled in what is actually a clinical trial.38 Both practices, to the extent that they exist, raise serious ethical concerns regarding informed consent, therapeutic misconception (mistaking participation in research as receiving clinical therapy and benefit), and exploitation of vulnerable patients.39,40\n\nIn this study, we sought to assess patients’ experiences with and attitudes towards ACBT, and their knowledge regarding associated legal and regulatory matters. The study seeks to provide evidence regarding how and why patients are accessing innovative regenerative medicines in a context that is fraught with scientific, legal, ethical and regulatory uncertainties, questions, and concerns.\n\nThe study advances and makes two important contributions to the existing literature on questions surrounding the clinical use of cell-based therapy products in the absence of regulatory authorization or high-quality evidentiary support. First, it is the earliest known examination of patient perspectives regarding cell-based therapy products that are within regulatory scope, in the sense that regulators have defined parameters for their authorization and use for clinical research and/or clinical management of medical conditions. Second, the study offers insights on how patients are experiencing the impacts of emerging regulatory frameworks for ACBT products and cell-based therapy products more generally. Both contributions provide a basis for analyzing associated ethical, legal and regulatory concerns, including concerns regarding pay-to-participate trials, informed consent, therapeutic misconception, and regulatory compliance. The study also provides data that different policymaking bodies, including governments, scientific bodies, and health professions regulators, can rely on to develop policies aimed at addressing ethical and regulatory compliance issues, and at improving the clinical experience of patients accessing ACBT.\n\n\nMethods\n\nEthics approval for this study was granted by the University of Alberta’s Research Ethics Board (Pro00128173). Participants provided full and voluntary consent to participate in the study and to the publication of the anonymous study results via a consent form approved by the University of Alberta’s Research Ethics Board. Participants read the consent form prior to completing the survey, and per the terms of the approved consent form, their consent to participate in the study was implied from the completion of the survey.\n\nThe study participants included individuals who received or were in the process of receiving treatments involving ACBT. Recruitment was conducted through posts on social media platforms, including Facebook, Twitter, LinkedIn, and Reddit.\n\nThe survey instrument explored participants’ knowledge about, perspectives of, and experiences with clinical procedures involving ACBT. The survey included a mix of questions eliciting quantitative and qualitative responses and took approximately 10 minutes to complete. The survey instrument is reproduced in the extended data.48\n\nThe survey was administered via Qualtrics. Data collection occurred for the duration of 11 days (06-17 March 2023). The survey was closed when the response rate reached what we considered optimal for analysis and no new responses had been received for two days. Following data collection, the initial dataset, consisting of 347 responses, was cleaned for analysis. Responses marked by Qualtrics as duplicates (n = 22), as likely bots (n = 101), and as both duplicates and likely bots (n = 5) were deleted from the dataset. Through manual data cleaning, any responses which were completely blank (n = 18) or had multiple nonsensical text entries were categorised as likely bots (n = 2) and were deleted from the dataset. We added a screening variable to ensure that participants had received ACBT. Seventeen participants indicated that the treatment they received did not involve taking cells, blood, or tissue from their own body, and one participant did not respond to the variable. We excluded these 18 participants based on the non-response or because it is likely they did not receive ACBT. The final dataset used for our analysis consisted of 181 responses. Among the 181 responses, missing data accounted for 1.3% of the values. As the percentage of missing values was below the 5% threshold that would likely affect the integrity of the dataset,41 they were ignored in the analysis. For items where participants were asked to “check all that apply”, the total number of responses is reported. The final dataset is available in underlying data.48\n\nThe quantitative survey data were analysed using SPSS 29. Chi-square tests were used to identify patterns in the quantitative data. Qualitative survey responses were analysed by identifying themes emerging from the data using NVivo 1.7.1. The data analyses were not pre-registered.\n\n\nResults\n\nParticipants were asked to report what type of ACBT they received, how they learned about it, where and in what facility they received it, which type of treatment provider administered it, why and for what condition they sought it, whether the ACBT was combined with another product, whether it was presented as a clinical trial or as a medical procedure, and whether there were any side effects. They were also asked about payment, including whether and how much they paid for the ACBT, and if and how they were reimbursed for the amount paid, and about whether their treatment provider discussed details with them concerning the purpose of cells being removed from their body and side effects from the ACBT.\n\nOf 181 participants, 53 (29.3%) reported that they received an autologous fat transplant, 48 (26.5%) received autologous human fibroblasts, 41 (22.7%) received an autologous serum therapy, 25 (13.8%) received autologous mesenchymal stem cells, and 14 (7.7%) received platelet-rich plasma. Of the 180 participants who responded to the variable regarding how they learned about the ACBT, 78 (43.3%) reported that they learned about the ACBT from the treatment provider, 47 (26.1%) were referred by a physician or clinic other than the treatment provider, 19 (10.6%) learned about it through social media, 16 (8.9%) received a referral from another healthcare provider (other than a physician or clinic), 12 (6.7%) learned about it through a clinic website, 4 (2.2%) through advertisements in a clinic, and 4 (2.2%) by word of mouth. Of 181 participants, public hospitals were the most common treatment facility (42.0%, n = 76), followed by specialists’ clinics (28.7%, n = 52), private hospitals (13.3%, n = 24), family doctors’ clinics (9.9%, n = 18), and walk-in clinics (6.1%, n = 11). Of 179 participants, most reported that their treatment provider was a doctor (89.9%, n = 161), while others reported that their treatment provider was a nurse practitioner (7.8%, n = 14), a nurse (1.7%, n = 3), or a physician assistant (0.6%, n = 1). Among 176 of the participants whose treatment provider was a doctor, their specialty was either in orthopaedics (46.0%, n = 81), sports medicine (31.8%, n = 56), plastic surgery (20.5%, n = 36), oncology (0.6%, n = 1), physiatry (0.6%, n = 1), or chiropractic medicine (0.5%, n = 1). Of 178 participants who responded, the majority received the ACBT in the U.S. (74.7%, n = 133), while the remainder received it in Canada (25.3%, n = 45). When asked to select all that apply, out of 260 selected responses, the reasons for seeking the ACBT varied with 106 (40.8%) participants reporting that their doctor or other healthcare provider recommended it, 82 (31.5%) indicated that they tried other treatments and they didn’t work, 39 (15.0%) indicated it was their only treatment option, 32 (12.3%) reported that a friend or family member recommended it, and 1 (0.4%) indicated that patients with their condition recommended it. Of 180 participants, the majority sought the ACBT for a sports injury (47.2%, n = 85) or osteoarthritis (36.7%, n = 66), while others sought it for cosmetic reasons (12.2%, n = 22) or other conditions (3.9%, n = 7). Three-quarters (76.2%, n = 138) of 181 participants reported that the ACBT was combined with another product, such as a medical device. The remainder of participants did not have an ACBT that was combined with another product (21.0%, n = 38) or were unsure (2.8%, n = 5).\n\nOf 181 participants, most reported that the ACBT was presented as a medical procedure (70.2%, n = 127), 45 (24.9%) participants reported that it was presented as a clinical trial, and 9 (5.0%) participants were unsure. Of 181 participants, 170 (93.9%) reported that the purpose of removing the cells, blood, or tissue from their body was explained to them, while 11 (6.1%) indicated that the purpose was not explained. Of 181 participants, while most did not report experiencing any side effects from the ACBT (60.2%, n = 109), 72 (39.8%) reported that they experienced side effects. Of 181 participants, the majority (86.7%, n = 157) indicated that the treatment provider informed them about any possible side effects. The remainder of participants either indicated that the treatment provider did not inform them (3.9%, n = 7) or that they didn’t remember (9.4%, n = 17).\n\nOf 181 participants, the vast majority reported paying for the ACBT (92.8%, n = 168), while 10 (5.5%) reported that they didn’t pay, and 3 (1.7%) didn’t remember. Among all of the participants who paid, most paid $100-$499 (39.9%, n = 67) or $500-$999 (32.7%, n = 55), while 37 (22.0%) paid $1000 or more. Only 9 (5.4%) paid $99 or less. All amounts were reported in Canadian Dollars. Among all of the participants who paid, 61 (36.3%) were reimbursed and 74 (44.0%) paid out-of-pocket. Thirty-three participants (19.6%) reported both being reimbursed and paying out-of-pocket. Out of 132 selected responses among those who received some degree of reimbursement, when asked to select all that apply, 61 (46.2%) participants indicated that they were reimbursed by government (public) health insurance, while 50 (37.9%) were reimbursed by private insurance through their employer, and 21 (15.9%) were reimbursed by private insurance not through their employer.\n\nParticipants indicated their knowledge of who the ACBT is regulated by and the evidence for the ACBT. They also reported whether their treatment provider discussed these details with them. Participants rated their confidence in knowing who to contact if they would like to make a complaint regarding the ACBT and shared their knowledge of who to contact.\n\nOf 176 participants, most indicated that the treatment provider discussed with them how the ACBT is regulated (88.6%, n = 156), while 8 (4.5%) participants indicated that it was not discussed, and 12 (6.8%) participants didn’t remember. When asked to select all that apply, out of 360 selected responses, 89 (24.7%) participants indicated that, to the best of their knowledge, the ACBT is regulated by a provincial medical regulatory authority, 88 (24.4%) indicated a provincial ministry of health, 77 (21.4%) indicated a federal regulatory authority, 41 (11.4%) indicated a federal medical regulatory authority, 31 (8.6%) indicated a research ethics board, 21 (5.8%) were unsure, and 13 (3.6%) indicated that there is no regulatory authority. In the event that they would like to make a complaint regarding the ACBT, 170 participants reported an average of 70.2% (SD = 21.2) confidence in knowing who to contact. When asked to select all that apply, out of 361 selected responses, most participants indicated that they would contact the clinic where they received the treatment procedure (37.4%, n = 135), 100 (27.7%) indicated a government regulator, 75 (20.8%) a research ethics board, and 51 (14.1%) the professional regulator. Of 180 participants, while 165 (91.7%) indicated that the treatment provider explained to them the evidence for the ACBT, 7 (3.9%) indicated that they did not, and 8 (4.4%) didn’t remember whether or not this was explained. When asked to select all that apply, to the best of their knowledge, out of 438 selected responses, 121 (27.6%) participants indicated that the evidence for the ACBT was the treatment provider’s clinical experience, 111 (25.3%) indicated peer-reviewed scientific research, 97 (22.1%) indicated patient testimonials, 64 (14.6%) indicated randomised controlled trials, and 45 (10.3%) indicated regulatory approval.\n\nParticipants reported whether they thought the ACBT should be provided without going through clinical trials or regulation and why or why not. They indicated whether they would recommend the ACBT and treatment procedure to someone else. Participants were asked whether and how their perception of the ACBT would change if they were to learn that it did not go through clinical trials and was not approved by a regulator.\n\nOf 179 participants, 74 (41.3%) indicated that they thought the ACBT should be provided without going through clinical trials or regulation and 105 (58.7%) disagreed. Participants provided 81 unique short answer text responses that expanded on their views. Sixteen of the participants who indicated that the ACBT should be provided without going through clinical trials or regulation provided reasons that were coded as relating to their beliefs (62.5%, n = 10), feelings (18.8% n = 3), subjective experiences (12.5% n = 2), or perspectives (6.3% n = 1). Among participants who shared their beliefs, 4 participants had beliefs regarding clinical trials, including the possibility of being assigned to a control group if they participate in a clinical trial and concerns about missing the best time for treatment given the lengthiness of clinical trials and regulatory approval. The remaining 6 participants were divided regarding whether they believed safety was a concern for ACBT. One participant expressed their feelings around the lack of safety, while two participants did not feel as though there is anything wrong with the ACBT. Two participants shared subjective experiences of the ACBT having helped them and one shared a perspective of wanting to give it a try regardless of undergoing clinical trials or regulatory approval.\n\nOf the participants who thought that the ACBT should not be provided without going through clinical trials or regulation, 57 shared reasons that were coded as relating to their beliefs (77.2%, n = 44), feelings (17.5%, n = 10), perspectives (3.5%, n = 2), or subjective experience (1.8%, n = 1). Safety was their primary concern. Participants mentioned safety both with regards to their beliefs about the role of clinical trials and regulation in determining safety (n = 23) and with regards to their subjective feelings of security and reassurance (n = 10). Participants also expressed that their responses stemmed from their beliefs regarding the professionalism of healthcare providers in upholding the rigour of medicine (n = 13) and the importance of regulation for ensuring accountability and reliability (n = 4). The remaining 4 participants shared beliefs regarding the role of clinical trials in ensuring efficacy, systemic responsibility for people’s health, and a belief that the technology is immature. Two participants shared their perspectives of not wanting to be tested on and one participant mentioned a subjective experience of pain.\n\nOf 180 participants, most indicated that they would recommend the ACBT to someone else (77.8%, n = 140), while 40 participants (22.2%) indicated that they would not recommend it.\n\nOf 180 participants, the majority indicated that if they were to learn that the ACBT they received did not go through clinical trials and was not approved by a regulator, it would change their perception of the ACBT (85.6%, n = 154), while the remainder (14.4%, n = 26) indicated that it would not change their perception of the ACBT. Of these participants, 85 followed up with unique short answer text responses to share how their perceptions would change or not change. Among 67 of the participants who indicated that their perception would change, their reasons were coded to be rooted in their beliefs (50.7%, n = 34), feelings (28.4%, n = 19), perspectives (14.9%, n = 10) or subjective experiences (6.0%, n = 4). Participants shared their beliefs regarding safety concerns (n = 18) and the lack of other treatments for their condition (n = 6). The remaining 10 participants shared beliefs of uncertainty about the efficacy of ACBT and high risk in the absence of regulation and in the absence of clinical trials. Participants expressed their feelings of uncertainty regarding ACBT safety (n = 15) and concerns around efficacy (n = 4). Ten participants shared their perspectives regarding hesitation to receive ACBT and four participants based their response on their subjective experiences, including having tried many other treatments or the ACBT being the only available treatment option.\n\nAmong 13 of the participants who indicated that their perception would not change, their reasons were coded as relating to their beliefs (38.5%, n = 5), perspectives (23.1%, n = 3), awareness (15.4%, n = 2), subjective experiences (15.4%, n = 2), or feelings (7.7%, n = 1). Participants’ beliefs included the lack of other options and were divided regarding the safety of the ACBT. The remainder of participants expressed their perspectives regarding the risk of missing the best time for treatment, their subjective experiences of having tried other treatments that were unsuccessful, and the efficacy of the ACBT.\n\nChi-square analyses identified statistically significant associations between several variables and the variable regarding whether participants received the ACBT as part of a clinical trial or a medical procedure. The facility where participants received the treatment procedure varied depending on whether they indicated receiving it as part of a clinical trial, or as a medical procedure, or were unsure, X2 (8, 181) = 39.73, p < .001. Among participants who reported receiving the ACBT as part of a clinical trial, 18 (40.0%) reported received it in a specialist’s clinic, 11 (24.4%) in a family doctor’s clinic, 6 (13.3%) in a public hospital, 5 (11.1%) in a private hospital, and 5 (11.1%) in a walk-in clinic. Participants who reported receiving the ACBT as a medical procedure were most likely to receive it in a public hospital (53.5%, n = 68), followed by 32 (25.2%) in a specialist’s clinic, 16 (12.3%) in a private hospital, 7 (5.5%) in a family doctor’s clinic, and 4 (3.1%) in a walk-in clinic.\n\nParticipants who received the ACBT as part of a clinical trial or as a medical procedure varied in whether the treatment provider discussed with them how the ACBT is regulated, χ2 (4, 176) = 10.80, p = .029. The majority of participants who indicated that they received the ACBT as part of a clinical trial reported having this information discussed with them (86.4%, n = 38), while 5 (11.4%) did not have this information discussed with them and 1 (2.3%) did not remember whether or not it was discussed. Participants who indicated that they received the ACBT as a medical procedure and reported having this information discussed with them were also in the majority (90.2%, n = 111), while 3 (2.4%) did not have this information discussed with them and 9 (7.3%) did not remember whether or not it was discussed.\n\nBased on whether they reported having received the ACBT within a clinical trial or as a medical procedure, participants differed in whether they thought the ACBT should be provided without going through clinical trials or regulation, χ2 (2, 179) = 20.40, p < .001. Participants who indicated that they received the ACBT as part of a clinical trial were more likely to think that ACBT should be provided without going through clinical trials or regulation (70.5%, n = 31) than participants who indicated that they received the treatment procedure as a medical procedure (31.7%, n = 40; Figure 1A). The same participants differed in whether they would recommend the ACBT to someone else, χ2 (2, 180) = 8.11, p = .017. Participants who indicated that they received the ACBT within a clinical trial were less likely to indicate that they would recommend the ACBT (63.6%, n = 28) than participants who indicated that they received the ACBT as a medical procedure (83.5%, n = 106; Figure 1B). Based on whether they reported having received the ACBT within a clinical trial or as a medical procedure, participants differed in whether their perception of the ACBT they received would change if they learned that the ACBT did not go through clinical trials and was not approved by a regulator, χ2 (2, 180) = 21.76, p < .001. Participants who indicated that they received the ACBT as part of a clinical trial were less likely to indicate that their perception would change (84.1%, n = 37) than participants who indicated that they received the ACBT as a medical procedure (89.8%, n = 114; Figure 1C).\n\nNon-significant statistical analyses were found between whether the ACBT was presented within a clinical trial or as a medical procedure and what type of ACBT participants received, how participants learned about the ACBT, who the treatment provider was, in what country they received the ACBT, whether or not the treatment provider informed them about any possible side effects of the ACBT, whether and how much they paid for the ACBT, whether the payment for the ACBT was reimbursed or paid out-of-pocket, and whether the evidence for the ACBT was explained.\n\nChi-square analyses also revealed that participants differed based on whether or not they paid for the ACBT. Participants’ reports of whether or not they paid for the ACBT varied with the condition for which they sought treatment, χ2 (6, 180) = 13.04, p = .042. Among participants who reported that they paid for the ACBT, 81 (48.5%) participants indicated that they sought treatment for a sports injury, 60 (35.9%) participants indicated that they sought treatment for osteoarthritis, 20 (12.0%) sought a cosmetic treatment, and 6 (3.6%) sought other treatments. Among participants who reported that they did not pay for the ACBT, 6 (60.0%) indicated that they sought treatment for osteoarthritis, 3 (30.0%) sought treatment for a sports injury, and 1 (10.0%) sought another treatment.\n\nParticipants who paid for the ACBT also differed from participants who did not pay with regards to whether their treatment provider discussed with them how the ACBT is regulated, χ2 (4, 176) = 48.99, p < .001. Participants who indicated that they paid for the ACBT were more likely to indicate that the treatment provider discussed with them how the ACBT is regulated (92.0%, n = 150) than participants who indicated that they did not pay for the ACBT (30.0%, n = 3).\n\nParticipants who paid for the ACBT differed from participants who did not pay with regards to whether or not they would recommend the ACBT to someone else, χ2 (2, 180) = 12.59, p = .002. Among participants who reported paying for the ACBT, 135 (80.8%) indicated that they would recommend the ACBT, while 4 (40.0%) participants who did not pay for the ACBT agreed with these views.\n\nStatistically non-significant results were found for analyses between whether or not participants paid for the ACBT and the type of ACBT they received, the facility where they received the ACBT, who the treatment provider was, in what country they received the ACBT, whether they thought the ACBT should be provided without going through clinical trials or regulation, and whether their perceptions of the ACBT would change if they learned that the ACBT they received did not go through clinical trials and was not approved by a regulator.\n\n\nDiscussion\n\nThis study surveyed participants who have received ACBT regarding their experiences, knowledge of the regulation and governance of ACBT, and perspectives of the clinical encounter. It explored issues pertaining to pay-to-participate trials, informed consent, and regulatory compliance. Several themes emerged from the data, including the prominent role of healthcare providers throughout the patient journey, informational practices during the clinical encounter, the high prevalence of pay-to-participate trials, patients’ gaps in regulatory knowledge, and patients’ priorities regarding clinical trials and regulation of ACBT.\n\nThe most commonly reported source through which participants learned about the ACBT was healthcare providers, with other sources such as clinic advertisements and websites, and social media playing a comparatively minor role. Treatment providers were mainly physicians. Our findings highlight the critical role of healthcare providers in providing patients with access to and information about the ACBT. Together, these findings suggest that physicians and healthcare providers play a key role in the patient journey and are at the forefront of the ACBT industry. These findings are consistent with previous studies that report the involvement of physicians in the clinical use and marketing of stem cell therapies ahead of regulatory authorization and supporting evidence.42,43\n\nAlthough it is not clear from the survey findings what specific side effects participants were informed about, the finding that the majority of participants were informed by their treatment providers about these side effects is encouraging as it indicates that treatment providers are cognizant of the need to discuss side effects that may be associated with an emerging therapy. The finding that the majority of the participants reported that their treatment providers discussed how ACBTs are regulated and the evidence for the treatment with them strengthens this conclusion. The latter indicates that providers recognize that the evidentiary and regulatory context for ACBT are an important point of emphasis for an emerging therapy that is receiving much social, scientific and regulatory attention and scrutiny. This is supported by our findings that patient perspectives are primarily driven by their beliefs about ACBT. A noteworthy caution is that the study did not assess the quality or accuracy of the information shared and discussed with participants. Medical regulatory authorities may be important for ensuring medical education for healthcare providers on providing and informing patients about ACBT.\n\nThe finding that the majority of participants reported that the treatment was presented as a medical procedure rather than a clinical trial is a signal to health product regulators regarding how the industry is operating. Given the push by regulators in some jurisdictions for clinical trials [Health Canada Policy Position Paper – Autologous Cell Therapy Products] and that the evidentiary and regulatory status of ACBTs remains unclear, it might also serve to alert health products and health professional regulators of the need to work together to ensure that treatment providers are complying with the requirement to conduct clinical trials for treatments that are not established scientifically.\n\nThe finding that some participants received reimbursement for treatment expenses from public and private health insurers is noteworthy as it suggests that insurers view ACBT as beneficial. In maintaining and expanding insurance coverage, care should be taken to align coverage with health technology assessments that weigh the cost of ACBT with its health and economic impacts, even in light of scientific support and regulatory approval.44\n\nAlthough the majority of participants in the study received ACBT as a medical procedure, a significant number reported having received the ACBT in a clinical trial in which they paid to participate (91.1%, n = 41). Of these, all but one participant paid $100 or more (97.6%, n = 40) and 21 (51.2%) participants paid out-of-pocket without any reimbursement. Pay-to-participate clinical trials raise a number of ethical concerns, including the skewing of clinical trial funding towards conditions affecting the wealthy, the exploitation of participants’ desire for a treatment, and compromising the scientific integrity of clinical trials.45–47 These concerns may be acute in the context of ACBT given that the majority of treatment providers are clinicians who may not ordinarily conduct clinical trials and are presumably only doing so mainly for purposes of regulatory compliance. Our findings suggest that regulators ought to be mindful of the ethical issues that may arise from regulatory enforcement initiatives, especially as they impact patient access to care and the conditions under which such care is received.\n\nWhile participants who received the ACBT as a medical procedure were more likely to think that it should go through clinical trials or receive regulatory approval before being provided, they also indicated that their perception of the treatment would change if they learned it had not gone through clinical trials or received regulatory approval. These responses suggest an assumption among participants that ACBT provided as medical procedures are under the purview of a regulatory body. Participants expressed a wide variability in what type of regulatory body they thought was responsible for regulating ACBT, with only a minority of them (21.4%, n = 77) correctly indicating that a federal regulatory authority (Health Canada and/or the US FDA) was responsible. Designing the regulatory system to be consistent with patients’ expectations of regulatory oversight therefore represents an important step in maintaining the trust of patients in ACBT.\n\nSafety emerged as a major theme of concern among participants, suggesting a public expectation for regulatory initiatives to prioritize safety. Regulations that address safety concerns may therefore be more likely to receive public support.\n\nWhile the use of an anonymous online survey had several advantages, including quick data collection from a broad sample of patients and minimization of self-reporting bias, these methods also limited our certainty in the authenticity of responses. The use of lottery draws may incentivize invalid responses for monetary gain. To minimize these risks, we removed any likely bot or duplicate responses from our analyses.\n\nThe study makes a novel contribution to the literature by providing the first analysis of patients’ experiences and perceptions of an emerging cell-based therapy within an evolving regulatory landscape. The findings serve as a valuable resource for developing policy, promoting scientific rigor, and ensuring ethical oversight of ACBT and other upcoming cell-based therapies. The study also highlights participants’ prioritization of the safety of ACBT while identifying critical gaps in their regulatory knowledge. Their experiences, knowledge, and perspectives provide critical insights towards the advancement of regulations pertaining to ACBT in Canada and the U.S. The important role of healthcare providers in how participants are informed about and receive ACBT warrants the involvement of provincial and state medical regulatory authorities in the regulation and enforcement of standards around informed consent, particularly among ACBT that are being provided as medical procedures. Conducting research on healthcare providers to explore their informed consent processes and pricing structure more thoroughly for ACBT may support recommendations for their regulation. To this end, our team is currently conducting a complementary study based on interviews with clinicians and clinical researchers who have sponsored ACBT in clinical trials in Canada and Australia. Our amplification of the patient voice by assessing their experiences, knowledge, and perspectives contributes a patient-centred perspective to the advancement of regulations pertaining to ACBT.",
"appendix": "Data availability\n\nOpen Science Framework: Clinical Use of Autologous Cell-Based Therapies in an Evolving Regulatory Landscape: A Survey of Patient Experiences and Perceptions (Dataset and Survey Questionnaire), https://doi.org/10.17605/OSF.IO/7RSJX. 48\n\nThis project contains the following underlying data:\n\n- S2 Appendix - Dataset.xlsx\n\nOpen Science Framework: Clinical Use of Autologous Cell-Based Therapies in an Evolving Regulatory Landscape: A Survey of Patient Experiences and Perceptions (Dataset and Survey Questionnaire), https://doi.org/10.17605/OSF.IO/7RSJX. 48\n\nThis project contains the following extended data:\n\n- S1 Appendix - Survey.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\nThe authors thank Amy Zarzeczny and Timothy Caulfield for their feedback on the design of the survey and for reviewing a draft manuscript. 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Publisher Full Text\n\nMaster Z, Resnik DB: Hype and public trust in science. Sci. Eng. Ethics. 2013; 19(2): 321–335. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTurner L: Preying on public fears and anxieties in a pandemic: Businesses selling unproven and unlicensed “stem cell treatments” for COVID-19. Cell Stem Cell. 2020; 26(6): 806–810. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHyun I, Lindvall O, Ahrlund-Richter L, et al.: New ISSCR guidelines underscore major principles for responsible translational stem cell research. Cell Stem Cell. 2008; 3(6): 607–609. PubMed Abstract | Publisher Full Text\n\nCaulfield T, McGuire A, Cho M, et al.: Research ethics recommendations for whole-genome research: consensus statement. PLoS Biol. 2008; 6(3): e73. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWerner M, Mayleben T, Bokkelen GV: Autologous cell therapies: the importance of regulatory oversight. Regen. Med. 2012; 7(6 Suppl): 100–103. PubMed Abstract | Publisher Full Text\n\nTabachnick BG, Fidell LS: Using multivariate statistics. 6th ed.Upper Saddle River: Pearson Education Inc.; 2013.\n\nOgbogu U, Du J, Koukio Y: The involvement of Canadian physicians in promoting and providing unproven and unapproved stem cell interventions. BMC Med. Ethics. 2018; 19(32): 32. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMurdoch B, Zarzeczny A, Caulfield T: Exploiting science? A systematic analysis of complementary and alternative medicine clinic websites’ marketing of stem cell therapies. BMJ Open. 2018; 8: e019414. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDriscoll D, Farnia S, Kefalas P, et al.: Concise review: The high cost of high tech medicine: Planning ahead for market access. Stem Cells Transl. Med. 2017; 6: 1723–1729. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTurner L, Snyder J: Ethical issues concerning a pay-to-participate stem cell study. Stem Cells Transl. Med. 2021; 10: 815–819. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEmanuel EJ, Joffe S, Grady C, et al.: Clinical research: Should patients pay to play? Sci. Transl. Med. 2015; 7(298): 1–5. Publisher Full Text\n\nWenner DM, Kimmelman J, London AJ: Forum Patient-Funded Trials: Opportunity or Liability? Cell Stem Cell. 2015; 17(2): 135–137. Publisher Full Text\n\nOgbogu U, Case N: Clinical Use of Autologous Cell-Based Therapies in an Evolving Regulatory Landscape: A Survey of Patient Experiences and Perceptions (Dataset and Survey Questionnaire). [Dataset]. 2023, August 8. Publisher Full Text"
}
|
[
{
"id": "223427",
"date": "15 Dec 2023",
"name": "Li Du",
"expertise": [
"Reviewer Expertise biotechnology law and policy"
],
"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 research is well-structured and written. It offers a unique viewpoint from patients who underwent the ACBT about their experience and comprehension of ACBT regulation’s legal aspects. I recommend accepting it for publication. However, I have two concerns regarding the discussion section where the authors discuss payment reimbursement for ACBT and improvements for clinical trials and regulations.\nThe authors’ assertion that insurers perceive ACBT as beneficial in the reimbursement section does not appear well-supported by the results. More explanation is needed to support this point. For improving regulations, safety is typically a fundamental principle for clinical trial regulations. Authors should further elaborate on this issue, explaining why the authors raised this concern. For example, are there regulations that place safety to a secondary role, or have certain regulations been improperly interpreted or enforced, thereby diminishing the importance of safety in favor of other considerations?\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? Yes",
"responses": [
{
"c_id": "10956",
"date": "22 Mar 2024",
"name": "Ubaka Ogbogu",
"role": "Author Response",
"response": "We are grateful to the reviewer for the positive feedback and for the comments on the article. We have provided responses addressing the reviewer's comments below, as follows: Reviewer comment: The authors’ assertion that insurers perceive ACBT as beneficial in the reimbursement section does not appear well-supported by the results. More explanation is needed to support this point. Our response: Thank you for this feedback. In the discussion section we suggested that insurers view ACBT as beneficial based on the finding that some participants are receiving reimbursement for treatment expenses from public and private health insurers. Generally, a criterion that health insurers (and health technology assessment reviews that inform reimbursement decisions) consider in deciding whether to reimburse the cost of a health intervention or drug is whether it provides a clinical benefit that is superior or comparable to existing treatment options (CADTH 2020; Nagase et al 2019). While it is not the only criteria (others include survival gains, cost and cost-effectiveness, clinical safety, improvement in surrogate outcomes, etc.), we use the notion of \"beneficial\" to link the finding that insurers are reimbursing ACBT costs to the notion that they do so because they believe, among other things, that it offers relative clinical benefit. We hope this explanation clarifies. Reviewer comment: For improving regulations, safety is typically a fundamental principle for clinical trial regulations. Authors should further elaborate on this issue, explaining why the authors raised this concern. For example, are there regulations that place safety to a secondary role, or have certain regulations been improperly interpreted or enforced, thereby diminishing the importance of safety in favor of other considerations? Our response: We have not raised the issue of safety as a \"concern\" in the discussion. Rather, we discussed the finding that safety emerged as a major theme of concern for the participants in the study (so, it was raised by the participants, not us) and we then reflected that this suggests a need to prioritize and address those safety concerns through future regulations. However, we note, in agreement with the reviewer, that it may be necessary to examine the extent to which extant regulations advance or fail to advance safety in the context of clinical trials of ACBT, and how safety regulations operate in practice or are perceived. This work, though important, is outside the scope of the current study. We are presently conducting other empirical studies with regulators and ACBT trialists where we examine how extant regulations, including safety regulations, shape and influence clinical trials and clinical uses of ACBT, and their perceptions of such regulations. We believe the results of the in progress study will answer some of the questions posed by the reviewer regarding the role that safety regulations play, and how they are perceived, within the context of ACBT clinical trials. Citations: CADTH (Canada's Drug and Health Technology Agency), Procedures for CADTH Reimbursement Reviews, January 2024, https://www.cadth.ca/sites/default/files/Drug_Review_Process/CADTH_Drug_Reimbursement_Review_Procedures.pdf Nagase, F.N.I., Stafinski, T., Sun, J. et al. Factors associated with positive and negative recommendations for cancer and non-cancer drugs for rare diseases in Canada. Orphanet J Rare Dis 14, 127 (2019). https://doi.org/10.1186/s13023-019-1104-7"
}
]
},
{
"id": "292492",
"date": "03 Jul 2024",
"name": "Yann Joly",
"expertise": [
"Reviewer Expertise Law",
"bioethics and public policy in modern 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\nThis manuscript presents an interesting study of patient experiences and perceptions of autologous cell-based therapy (ACBT) procedures. The piece is clear and well written it is informative of the type of patients interested in these procedures in North America, and about the procedures themselves. The context information provided, while succinct, is recent and accurate. It is surprising to me that the authors did not choose to collect a minimal set of demographic information about their respondents, age range, sex, education level, for example, which would have provided a much richer dataset. In the same vein, it is unclear whether they retained the information about countries of origin (U.S., Canada). If they did, it was not included in the analysis parameters they used. Given that the survey was anonymous, were the authors able to filter out potential duplicates? (Participants that may have responded twice or more to the questionnaire). Were respondents compensated for their responses or was the contribution non remunerated? I would have also liked to have more information on whether the quantitative data obtained was statistically significant or sufficiently representative of the U.S./Canadian population of patients seeking ACBT. This seems unlikely and it would be important to disclose this study limitation. In the discussion section, the authors make the most of their data providing interesting interpretations and inferences for their results. I have some reserve about the positive inference made by the authors about international practices during the clinical encounter. The fact that service providers participating in a generally fraudulent practice, can speak to some of its basic regulatory and mechanistic concepts with customers is hardly reassuring, it simply makes their otherwise false representations more believable to them. The findings about the (growing?) importance of the pay-to-participate type of stem cell clinical trials and, that of reimbursement payments for ACBT procedures are much more interesting and warrant further exploration. In sum a good short manuscript, to keep up with the fraudulent stem cell businesses ethical challenge. The study itself make for a good pilot that could be further developed to be used more widely. If so, please make sure to collect some demographic data with the responses. This manuscript presents an interesting study of patient experiences and perceptions of autologous cell-based therapy (ACBT) procedures. The piece is clear and well written it is informative of the type of patients interested in these procedures in North America, and about the procedures themselves. The context information provided, while succinct, is recent and accurate. It is surprising to me that the authors did not choose to collect a minimal set of demographic information about their respondents, age range, sex, education level, for example, which would have provided a much richer dataset. In the same vein, it is unclear whether they retained the information about countries of origin (U.S., Canada). If they did, it was not included in the analysis parameters they used. Given that the survey was anonymous, were the authors able to filter out potential duplicates? (Participants that may have responded twice or more to the questionnaire). Were respondents compensated for their responses or was the contribution non remunerated? I would have also liked to have more information on whether the quantitative data obtained was statistically significant or sufficiently representative of the U.S./Canadian population of patients seeking ACBT. This seems unlikely and it would be important to disclose this study limitation. In the discussion section, the authors make the most of their data providing interesting interpretations and inferences for their results. I have some reserve about the positive inference made by the authors about international practices during the clinical encounter. The fact that service providers participating in a generally fraudulent practice, can speak to some of its basic regulatory and mechanistic concepts with customers is hardly reassuring, it simply makes their otherwise false representations more believable to them. The findings about the (growing?) importance of the pay-to-participate type of stem cell clinical trials and, that of reimbursement payments for ACBT procedures are much more interesting and warrant further exploration. In sum a good short manuscript, to keep up with the fraudulent stem cell businesses ethical challenge. The study itself make for a good pilot that could be further developed to be used more widely. If so, please make sure to collect some demographic data with the responses.\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": "12231",
"date": "27 Aug 2024",
"name": "Ubaka Ogbogu",
"role": "Author Response",
"response": "Reviewer: This manuscript presents an interesting study of patient experiences and perceptions of autologous cell-based therapy (ACBT) procedures. The piece is clear and well written it is informative of the type of patients interested in these procedures in North America, and about the procedures themselves. The context information provided, while succinct, is recent and accurate. It is surprising to me that the authors did not choose to collect a minimal set of demographic information about their respondents, age range, sex, education level, for example, which would have provided a much richer dataset. Response: We initially considered collecting demographic information but decided against it for two main reasons. First, to minimize the risk of “survey fatigue” and to improve response rates and data quality, we shortened the questionnaire to focus solely on questions directly related to our research objectives. Survey fatigue is a well-documented issue, particularly during the COVID-19 pandemic [1-5]. Second, while demographic data could provide insights into how demographic variables influence perceptions, we determined that our research questions could be answered without it. Additionally, our analysis did not rely on demographic factors or treat the responses as representative of any specific population of patients seeking ACBT. However, we acknowledge the reviewer’s point and will incorporate demographic information in future studies on this topic. Reviewer: In the same vein, it is unclear whether they retained the information about countries of origin (U.S., Canada). If they did, it was not included in the analysis parameters they used. Response: We did not collect information regarding the country of origin, as it was not necessary for answering our research question. However, we did gather data on the country where respondents received ACBT, which is detailed in the “Results” section under “Part 1: Summary of Participants’ Experiences.” Reviewer: Given that the survey was anonymous, were the authors able to filter out potential duplicates? (Participants that may have responded twice or more to the questionnaire). Response: Yes, duplicates were filtered out by Qualtrics and through manual screening. We have already mentioned this process in the Methods section of the paper. Additionally, we noted in the Limitations section that “we removed any likely bot or duplicate responses from our analysis.” Reviewer: Were respondents compensated for their responses or was the contribution non remunerated? Response: Survey respondents were entered into a lottery draw for a chance to win a $50 CAD gift card. This incentive was approved by the University of Alberta Research Ethics Board. One respondent received the incentive. We already noted the lottery draw in the Limitations section, but we have also updated the Methods section to clearly note the incentive. Reviewer: I would have also liked to have more information on whether the quantitative data obtained was statistically significant or sufficiently representative of the U.S./Canadian population of patients seeking ACBT. This seems unlikely and it would be important to disclose this study limitation. Response: We have included a statement in the Limitations section to address this comment. The statement reads: “The quantitative data reported in this study is not sufficiently representative of the population of patients seeking ACBT in the U.S. and Canada. Therefore, the data should not be interpreted as generalizable to this population.” Reviewer: In the discussion section, the authors make the most of their data providing interesting interpretations and inferences for their results. I have some reserve about the positive inference made by the authors about international practices during the clinical encounter. The fact that service providers participating in a generally fraudulent practice, can speak to some of its basic regulatory and mechanistic concepts with customers is hardly reassuring, it simply makes their otherwise false representations more believable to them. Response: We are grateful to the reviewer for this observation. We have added a statement in the Discussion section to acknowledge the comment. Reviewer: The findings about the (growing?) importance of the pay-to-participate type of stem cell clinical trials and, that of reimbursement payments for ACBT procedures are much more interesting and warrant further exploration. Response: We are grateful to the reviewer for this observation and will keep it in mind for further exploration. Reviewer: In sum a good short manuscript, to keep up with the fraudulent stem cell businesses ethical challenge. The study itself make for a good pilot that could be further developed to be used more widely. If so, please make sure to collect some demographic data with the responses. Response: Noted. We will endeavour to address this comment in future studies. Thank you! References Lavrakas, P. J. (2008). Respondent fatigue. In Encyclopedia of Survey Research Methods (pp. 743-743). SAGE Publications, Inc., https://doi.org/10.4135/9781412963947. Galesic, M., & Bosnjak, M. (2009). Effects of Questionnaire Length on Participation and Indicators of Response Quality in a Web Survey. The Public Opinion Quarterly, 73(2), 349–360. http://www.jstor.org/stable/25548084 Herzog, A. R., & Bachman, J. G. (1981). Effects of Questionnaire Length on Response Quality. The Public Opinion Quarterly, 45(4), 549–559. http://www.jstor.org/stable/2748903 Jeong, D., Aggarwal, S., Robinson, J., Kumar, N., Spearot, A., & Park, D. S. (2023). Exhaustive or exhausting? Evidence on respondent fatigue in long surveys. Journal of Development Economics, 161, 102992. De Koning, R., Egiz, A., Kotecha, J., Ciuculete, A. C., Ooi, S. Z. Y., Bankole, N. D. A., ... & Kanmounye, U. S. (2021). Survey fatigue during the COVID-19 pandemic: an analysis of neurosurgery survey response rates. Frontiers in surgery, 8, 690680."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1165
|
https://f1000research.com/articles/12-1200/v1
|
25 Sep 23
|
{
"type": "Research Article",
"title": "COVID-19 Vaccine: Predicting Vaccine Types and Assessing Mortality Risk Through Ensemble Learning Agorithms",
"authors": [
"Hind Monadhel",
"Ayad R. Abbas",
"Athraa Jasim Mohammed",
"Ayad R. Abbas",
"Athraa Jasim Mohammed"
],
"abstract": "Background: There is no doubt that vaccination is crucial for preventing the spread of diseases; however, not every vaccine is perfect or will work for everyone. The main objective of this work is to predict which vaccine will be most effective for a candidate without causing severe adverse reactions and to categorize a patient as potentially at high risk of death from the COVID-19 vaccine. Methods: A comprehensive analysis was conducted using a dataset on COVID-19 vaccine adverse reactions, exploring binary and multiclass classification scenarios. Ensemble models, including Random Forest, Decision Tree, Light Gradient Boosting, and extreme gradient boosting algorithm, were utilized to achieve accurate predictions. Class balancing techniques like SMOTE, TOMEK_LINK, and SMOTETOMEK were incorporated to enhance model performance. Results: The study revealed that pre-existing conditions such as diabetes, hypertension, heart disease, history of allergies, prior vaccinations, other medications, age, and gender were crucial factors associated with poor outcomes. Moreover, using medical history, the ensemble learning classifiers achieved accuracy scores ranging from 75% to 87% in predicting the vaccine type and mortality possibility. The Random Forest model emerged as the best prediction model, while the implementation of the SMOTE and SMOTETOMEK methods generally improved model performance. Conclusion: The random forest model emerges as the top recommendation for machine learning tasks that require high accuracy and resilience. Moreover, the findings highlight the critical role of medical history in optimizing vaccine outcomes and minimizing adverse reactions.",
"keywords": [
"Classification algorithm",
"COVID-19 Vaccine",
"ensemble learning",
"machine learning",
"Sampling methods",
"Side effects."
],
"content": "Introduction\n\nFrom seven to 13 years of research and development (R&D) and 1.8 million clinical trials to develop a vaccine in the past, we have transitioned to 10 to 18 months of R&D and tens of thousands of clinical trials to start vaccinating against COVID-19 in 2021.1\n\nVaccines are biologics that provide active adaptive immunity against particular diseases. The vaccine usually contains drugs similar to the microorganisms that cause the disease. It is generally made from one of the killed or attenuated micro-organisms, its toxins, or its surface proteins. Giving us an injection, nasal spray, or oral vaccine stimulates our immune system to recognize and destroy foreign bodies.2\n\nAs a result of the novel coronavirus's rapid dissemination and disease burden, pharmaceutical companies and researchers were forced to create vaccinations quickly using either novel or preexisting technologies.3 There are several different types of vaccines, and the purpose of each type is to boost your immune system and prevent serious, life-threatening diseases from occurring.4 The COVID-19 vaccines that have been approved employ a variety of mechanisms of action, including mRNA, DNA vaccines, viral vectors, protein subunits, and virus-inactivated vaccination techniques.5 Three vaccines have been widely administered: Pfizer and Moderna (mRNA) vaccinations targeting the SARS-CoV-2 surface protein, and the Janssen (viral vector) vaccine, which employed pre-existing technology with an adenovirus vector to trigger an immune response and provide protection against further infection. As these vaccines were developed using various approaches, they differ in efficacy and storage conditions.6\n\nHowever, no vaccine is entirely free from complications or adverse reactions. Any vaccination can have early adverse reactions, including local ones like pain, swelling, and redness, as well as systemic ones like headache, chills, nausea, fatigue, myalgia, and fever.7 Also, several existing health conditions or symptoms the candidate already has can lead to severe adverse reactions after taking the COVID-19 vaccine. The candidate's death could be the worst-case scenario. As a result, it's critical to know about the candidate's previous medical history.8\n\nThis work's main contribution can be summarized as follows:\n\n1. Identify the most important features of an individual's medical history that could contribute to adverse reactions to vaccination.\n\n2. Identify the most important features that contributed to the death of the candidate based on his or her medical history.\n\n3. Address the challenge of the imbalanced dataset by employing sampling methods to effectively handle the imbalance and improve the reliability of the analysis.\n\n4. Develop a machine learning (ML) model capable of predicting and classifying the most suitable vaccine types for each candidate, thus helping to prevent severe consequences and ensure optimal vaccination outcomes.\n\nThe rest of this paper is organized as follows: In the next section, we discuss a brief review of the literature on various related works. Section 3, provides a detailed explanation of our methodology and dataset. In Section 4, we discuss the study findings. while Section 5 discusses conclusions and potential future research.\n\n\nLiterature review\n\nDue to the rapid advancement of technology, there are numerous opportunities and possibilities for ML in healthcare.9 Classification is the most well-known machine-learning technique in medical applications because it is similar to everyday problems. A classification algorithm builds a model based on training data and then applies it to test data to obtain a prediction.10\n\nInterestingly, some studies have utilized machine learning applications to predict side effects, reactogenicity, and morbidity incidence following COVID-19 vaccinations. In research by Sujatha et al.,,11 the authors develop a model to predict whether a candidate is suitable for COVID-19 vaccination. In this paper, four machine learning approaches named Logistic Regression, AdaBoost, Random Forest, and Decision Tree were employed in the task of prediction. The authors found that AdaBoost was the classifier with the best performance, with 0.98 accuracies.\n\nIn research by Hatmal. M et al.,12 the authors used machine learning and ensemble methods to predict the severity of side effects, defined as no, mild, moderate, or severe side effects. The analysis revealed that random forest and XGBoost achieve the highest accuracy (0.80 and 0.79, respectively) and Cohen’s κ values (0.71 and 0.70, respectively). Statistical data analysis has revealed that the side effects were significantly different based on vaccine type. According to this study, the COVID-19 vaccine that the centers for disease control and prevention (CDC) has approved is safe, and vaccination provides people with a sense of safety. However, a severe case may need additional medical care or even hospitalization.\n\nIn research by Lian et al.,13 the goal was to collect and analyze tweets about the COVID-19 vaccination to find posts about personal experiences with COVID-19 vaccine adverse events. The authors found that the ensemble model-based RF achieves the best performance with an F1 score of 0.926, an accuracy of 0.908, and a recall of 0.946. The named entity recognition (NER) model achieved an F1 score of 0.770 for detecting adverse events using the conditional random fields (CRF) algorithm. Also, the results show that the three COVID-19 vaccines' (Pfizer, Moderna, and Johnson & Johnson) most common side effects are soreness to touch, fatigue, and headache.\n\n\nMethods\n\nThe overview of the general methodology for developing a machine learning models is visualized in Figure 1. In this study, we focus on predicting which vaccine will be most effective for a candidate without causing severe adverse reactions (output) based on several factors (input) and handling the imbalanced data that falls under the Pre-processing step where the data preparation process takes place.\n\nThe raw data of individuals who received vaccinations and reported adverse reactions was obtained from the VAERS.14 This dataset contains vaccination information for individuals vaccinated against a variety of diseases including COVID-19, Polio, Tetanus, and Influenza. However, our current study omitted any non-SARS-CoV-2 (COVID-19) vaccination information. Therefore, the dataset being used consists of 49,810 individuals. This dataset has various attributes of individuals’ information such as age, gender, current illness, medical history, allergic history, type of vaccine, life-threatening illness, symptoms after vaccinations, etc. Some of these attributes have been found to be textual (e.g., medical history, symptoms text, etc.), while others have been found to be numerical (such as age, number of doses, etc.). The description of some different attributes in the VAERS data set is illustrated in Table 1.\n\nThe quality of raw data used to perform any analysis heavily influences its outcome. Therefore, the preprocessing and exploratory analysis of data becomes the most important parts of any data-driven investigation. The preprocessing of a dataset involved examining the data for missing values, irrelevant values, replicas, etc. whereas EDA assists in understanding data by visualizing it. It has been noticed that the dataset contains many missing and irrelevant values.\n\nAny COVID-19 vaccine types that were not specified were removed, and only two types of values in the sex field were considered: “M” as male and “F” as female. Unknown values were excluded. In the died field, ‘Y’ was considered yes, and the rest were considered ‘no’; in the ‘prior vaccine’ field, ‘yes’ was considered yes, and the rest were considered ‘no’. The analysis of allergic history included considering mentioned allergic effects as positive cases and considering ‘null’, ‘none’, ‘NA’, and other negatively mentioned text as negative cases. The History column in the dataset contained written records of coexisting conditions, requiring the extraction of all of the patient's medical history separately. To better understand the patient's medical history, information about pre-existing chronic and non-chronic diseases, such as chronic obstructive pulmonary disease, hypertension, diabetes, and kidney disease, was extracted. All missing values (i.e., empty, null) were excluded from this field, and spelling/grammar mistakes were fixed.\n\nIn the Feature extraction step, most of the important features in the acquired dataset are presented as textual data. However, in order to analyze them, they must be separated into separate entities. As a result, String matching was used to convert all text data into attributes. The correlation plot (Figure 2) did not demonstrate a significant relationship between various attributes and vaccine types. Yet, previous studies revealed a direct correlation between vaccine adverse reactions and medical and allergic histories. Therefore, the number of unique entries for the diseases in the patient's medical histories was counted. Diseases with more than 300 counts in patients' medical histories were considered attributes, while the rest were ignored due to the large dataset and the computational burden associated with each individual disease. This study, therefore, considered 21 diseases which are diabetes mellitus, thyroid, different pain, obesity, migraine, kidney disease, hypertension, hyperlipidemia, high cholesterol, heart disease, Gastroesophageal Reflux Disease (GERD), depression, dementia, positive history of COVID-19, Chronic Obstructive Pulmonary Disease (COPD), cancer, atrial fibrillation, asthma, arthritis, anxiety, and anemia from the patient’s medical history as attributes. Using the VAERS id, these files have been merged into one file after identifying and extracting features. The analyzed dataset has 28 different features and over 49,810 samples. The data was encoded using a one-hot encoding technique.\n\nIn this study, only three methods of handling imbalanced data are used. In the first place, no changes are made to the data. Normally, it is divided into training and testing data at a ratio of 8 to 2. This first technique is referred to as “Normal” in this study. Next, experiments are conducted using well-known imbalanced data techniques called SMOTE, Tomek-links, and SMOTETOMEK, for balancing the dataset which combines SMOTE and Tomek links.15 As with the previous experiment, the dataset is divided into training and testing data at a ratio of 8 to 2. This experiment aims to handle imbalanced data and further improve the performance of machine learning classification models, especially in the multiclass classification scenario.\n\nTo predict which vaccine will be most effective for a candidate without causing severe adverse reactions (output) based on several factors (input), different machine-learning algorithms were used to build the proposed model.\n\nRandom Forest (RF)\n\nA multipurpose data mining approach for classification. It is based on decision trees that operate as an ensemble, an approach of combining multiple classifiers to identify problems and enhance accuracy. A classification is predicted by each tree independently, and votes for the relevant class, and the majority of votes decide the model’s prediction. It can handle large dataset with high dimensionality, it also improves the accuracy of the model and eliminates the overfitting problem.16\n\nDecision Tree (DT)\n\nA DT is a supervised learning technique that can be used for classification and regression problems; however, it is most commonly used to resolve classification issues. In this tree-organized classifier, the internal nodes represent datasets, branches represent decision rules, and each leaf node represents the outcome. A DT has two nodes: the decision node and the leaf node. The leaf nodes are the result of such decisions and they do not have any extra branches, but decision nodes are frequently used to settle any decision and have several branches. Based on the features of the dataset, decisions or tests are made.17\n\nExtreme Gradient Boosting (XGB)\n\nXGBoost is an ensemble learning method combining multiple weak models' predictions to generate a stronger prediction. In the beginning, XGB fits the data to a weak classifier. Afterward, the data is fitted to another weak classifier to increase accuracy without affecting the current model. In the same way, the process continues until the best accuracy is achieved.18 Furthermore, XGBoost supports parallel processing, making it possible to train models on large datasets in a reasonable period of time.\n\nLight Grading Boosting Machine (LGBM)\n\nLGBM is an open-source gradient boosting algorithm based on a tree-based learning framework; it is an open-source GBDT algorithm designed by Microsoft Research Asia. This framework grew trees vertically (leaf-wise) rather than horizontally (level-wise) as other tree-based frameworks did. Therefore, it can reduce the losses more efficiently and handle huge dataset with less computational complexity due to its lighter version.19\n\nMacro average and Weighted Average are used to calculate the performance of the four classifiers used for learning.\n\n• Accuracy: This term tells us how many classifications were correct out of all classifications.\n\n• Precision: A model's precision tells us how reliable its predictions are.\n\n• Recall: The model's ability to detect class.\n\n• F-score: It will give us a harmonic mean of precision and recall.\n\n• ROC Curve & AUC\n\nROC Curves show the performance of the classification model across all classification thresholds. In a ROC curve, the TP rate and FP rate are plotted at each threshold of classification. “AUC” stands for “Area Under the ROC Curve”. It can be used as a classifier to distinguish between classes. In general, the higher the AUC value, the better the classifier is at identifying positive from negative classes.20,21\n\n\nResults and Discussion\n\nThe majority of the individuals, 74% in total, were identified as female It was estimated that the average age of the individuals was about 53 years old and that the average age of those who died was about 72 years. Thus, there is a noticeable age difference between the two groups. Regarding reported chronic diseases, chronic hypertension held the highest prevalence (13%), followed by asthma (12%), and kidney and anemia (2%) (Figure 4). Among those who experienced adverse effects from vaccination, 10.7% lost their lives. From (Figure 3), one can clearly observe that in both genders, the majority of case fatalities occurred in individuals between the ages of 70 and 89. It should also be noted that the mortality rate of males is significantly higher than that of females from the age of 60 to 99 years. Hence, men are suffering from more significant adverse effects that lead to death.\n\nExtensive experiments have been conducted to predict three significant events in COVID-19 vaccination according to different scenarios. ML’s most relevant model to classify vaccines in each scenario includes RF, DT, XGB, and LGBM. We used 80% training data and 20% test data to evaluate the effectiveness of different ML-based approaches. As was previously mentioned, this dataset was unbalanced; therefore, We employed sampling strategies to address this problem. A number of well-known performance measures were used to assess the results of classification, including accuracy, precision, recall, F1 score, and ROC-AUC.\n\nOur results are presented in two parts each with two scenarios: (a) multiclass classification with sampling, (b) binary classification with sampling, and (c) a comparison of the best model for each part.\n\nThis section presents the results of the multiclass classification for covid-19 vaccine predicting problem, along with the analysis and the discussion. Firstly, we considered the patient’s medical history as independent features and the vaccine type (value 0 means Moderna, 1 means Pfizer, and 2 means Janssen) as dependent features that depend on the independent features. Then each of the three data-sampling procedures—SMOTE, TOMEK-LINKS, and SMOTETOMEK—was applied separately. (Figure 5) illustrates the effects of applying various data-balancing techniques.\n\nThe performance parameters for each model on the test dataset are presented in (Table 2). As a result, the following observations have been noted:\n\n• The testing accuracy values range from approximately 75% to 81% across different models and methods. The Random Forest (RF) models with Normal, TOMEK-LINKS, and SMOTETOMEK methods achieved the highest testing accuracy of around 80.8%, while the XGBoost (XGB) and LightGBM (LGBM) models with Normal, SMOTE, and TOMEK-LINKS methods achieved slightly lower testing accuracy, ranging from 75.2% to 76.2%.\n\n• The training accuracy values are relatively close to the testing accuracy values, indicating that the models are not overfitting to the training data. The training accuracy values range from approximately 76.9% to 81.2%.\n\n• Macro Precision, Recall, and F1 Scores: These metrics provide insights into the models' performance for each class, and the macro averaging considers all classes equally. The RF and DT models consistently show similar precision, recall, and F1 scores across different methods, ranging from around 78.9% to 81.6%. The XGB and LGBM models tend to have slightly lower scores, ranging from approximately 70.5% to 74.6%. The RF models generally achieve the highest scores, while the XGB and LGBM models have the lowest scores.\n\n• The AUC (Area Under the Curve) values represent the performance of the models in terms of their ability to rank samples correctly across all classes. The AUC values range from approximately 78% to 85%. The RF models with SMOTE and SMOTETOMEK methods achieved the highest AUC values of around 85%, indicating better overall performance in distinguishing between different vaccine types.\n\n• Overall, the RF models consistently perform well across different methods, with relatively higher accuracy, precision, recall, F1 scores, and AUC values. The XGB and LGBM models have lower performance compared to RF and DT models. The SMOTE and SMOTETOMEK methods generally improve the performance of the models, as seen in higher AUC values compared to the Normal and TOMEK-LINKS methods. These models achieve relatively high testing accuracy, balanced precision, recall, and F1 scores, as well as high AUC values.\n\nROC curves have been used to further analyze the predictive capability of these developed models, which are shown in (Figure 6). The RF and DT models prove their effectiveness. Taking AUC into account, all developed models perform satisfactorily.\n\nIn our model’s analysis, firstly, we considered the patient’s medical history as the independent features, and the vaccine type (value 0 means Moderna and value 1 means Pfizer) and the patient death (value 0 mean alive, and value 1 mean died) as dependent features. We trained and evaluated our models using test data by measuring accuracy, precision, recall, and AUC.\n\nScenario 1: Based upon both medical history and vaccine type\n\nThe performance parameters for each model on the test dataset are presented in (Table 3). As a result, the following observations have been noted:\n\n1. RF achieved high testing accuracy (0.87091) and training accuracy (0.87439), indicating good generalization and low overfitting. It demonstrated high precision (0.87974), recall (0.87091), and F1 score (0.87424), suggesting a balanced performance between identifying positive and negative instances. The AUC (0.93) indicates a high discriminatory power of the model. The precision value for both RF and DT was reported as 0.87. XGB and LGBM also show a comparable precision value of 0.86 and 0.0.84, respectively.\n\n2. DT achieved similar testing accuracy (0.86975) and training accuracy (0.87439) as RF. It showed slightly lower precision (0.8779), recall (0.86975), and F1 score (0.8728) compared to RF. The AUC (0.93) suggests a good ability to distinguish between positive and negative instances.\n\n3. XGB achieved a slightly lower testing accuracy (0.85905) and training accuracy (0.86122) compared to RF and DT. It demonstrated comparable precision (0.86031), recall (0.85905), and F1 score (0.8596) to the testing accuracy, indicating a balanced performance. The AUC (0.91) suggests a reasonably good ability to discriminate between positive and negative instances.\n\n4. LGBM showed the lowest testing accuracy (0.84953) and training accuracy (0.85038) among the models. It had slightly lower precision (0.84771), recall (0.84953), and F1 score (0.84857) compared to the other models. The AUC (0.89) suggests a good ability to distinguish between positive and negative instances, although it is lower than RF and DT.\n\n5. The RF and DT models with vaccine-type target consistently achieved the highest accuracy, Recall, Precision, F1 score, and AUC, especially RF outperforms all others. XGB and LGBM models had slightly lower performance metrics but still maintained reasonable accuracy and AUC.\n\n6. Thus, the experimental analysis recommends the RF model is the most suitable for detecting vaccine type compared to the other models.\n\nROC curves have been used to further analyze the predictive capability of these models, which are shown in (Figure 7). The RF and DT models prove their effectiveness. Taking AUC into account, all developed models perform satisfactorily.\n\nScenario 2: based upon both medical history and death\n\nThe patient’s death dataset was also experimented with as the vaccine-type dataset. (Figure 8) demonstrates the effect of applying various data-sampling methods. The performance parameters for each model on the test dataset are presented in (Table 4). As a result, the following observations have been noted:\n\n1. The testing accuracy values range from approximately 79.9% to 85.7%, depending on the model and method used. The RF and XGB models consistently achieve higher testing accuracy compared to DT and LGBM models. Among the methods, TOMEK-LINKS and SMOTETOMEK methods tend to show slightly lower testing accuracy compared to Normal and SMOTE methods.\n\n2. The training accuracy values are relatively high, ranging from approximately 87% to 95.2%. However, there is a notable difference between the training accuracy and testing accuracy values, suggesting potential overfitting issues, especially for the RF models.\n\n3. Precision, Recall, and F1 scores: The precision, recall, and F1 scores provide insights into the models' performance for predicting the positive class (death possibility). The RF models consistently achieve higher precision, recall, and F1 scores compared to DT, XGB, and LGBM models. Among the methods, TOMEK-LINKS and SMOTETOMEK methods tend to show slightly lower precision, recall, and F1 scores compared to Normal and SMOTE methods.\n\n4. The AUC (Area Under the Curve) values represent the models' ability to rank samples correctly and discriminate between positive and negative classes. The AUC values range from approximately 66% to 86%. The RF and XGB models consistently achieve higher AUC values, indicating better overall performance in distinguishing between COVID-19 death possibilities.\n\n5. the models trained on the normal data generally performed better in terms of accuracy and AUC compared to the models trained on the modified datasets (SMOTE, TOMEK-LINKS, SMOTETOMEK). The Random Forest, XGBoost, and LGBM models consistently showed good performance across the metrics in all datasets, indicating their robustness and effectiveness in classification tasks. The Decision Tree model had relatively lower performance, especially in terms of AUC, in all methods.\n\nROC curves have been used to further analyze the predictive capability of these models, which are shown in (Figure 9). The RF and DT models prove their effectiveness. Taking AUC into account, all developed models perform satisfactorily.\n\nThe importance of all the features in the COVID-19 vaccine adverse reactions dataset is calculated using the feature_importance package from the Scikit-learn Python library. A visual representation of the calculated values for feature importance is displayed in Figure 10. The features are arranged based on their respective importance scores.\n\nFigure 10 shows that patients' age, gender, and use of other medicines were significant factors in the past medical history of all target variables. WHEN examining the target variable of “vaccine type,” the analysis revealed a comprehensive set of critical attributes within the patient's medical history that strongly influence the selection of the administered vaccine. These attributes include previous vaccine history, allergic history, diabetes, arthritis, hypertension, and asthma. Furthermore, when investigating the target variable of death status, certain factors emerged as highly significant. These factors include heart disease, allergic history, dementia, hypertension, diabetes, kidney disease, and Chronic obstructive pulmonary disease (COPD). These attributes have shown a noteworthy impact on the desired outcome, indicating their importance in predicting the death status of patients.\n\nThe patient's age and gender provide essential demographic information that may impact the choice of vaccine, as certain vaccines have age or gender-specific recommendations. Additionally, considering the patient's current medication usage is crucial to ensure compatibility and potential interactions with the chosen vaccine. Previous vaccine history helps determine if the patient requires a booster or a specific type of vaccine.\n\nThe presence of underlying conditions such as diabetes, arthritis, allergic history, hypertension, and asthma is highly influential in the decision-making process. These conditions may affect the patient's immune response or make them more susceptible to certain vaccine side effects. By considering these attributes, healthcare professionals can tailor the vaccine type to maximize efficacy and minimize risks for each patient.\n\nAs far as the authors are aware, this is the first study that attempts to predict the type of covid-19 vaccine appropriate for a candidate, along with the death probability risk. Additionally, we suggest approaches to address the issue of imbalanced data concerning adverse reactions to COVID-19 vaccines.\n\nThis study has some limitations. Because these data were collected online, we cannot rule out information-gathering bias in the study. Moreover, this data set contained a significant amount of missing data, which may lead to a misrepresentation of patient populations.\n\n\nConclusion and future works\n\nIn this work, four ML models were evaluated: DT, RF, XGBoost, and LGBM. Three sampling techniques were executed for each model to handle imbalanced data. Below are some of the key findings of the study, which shed light on crucial insights and implications:\n\n1. The tree-based model RF presented the best overall results with multiclass classification.\n\n2. The SMOTE and SMOTETOMEK methods generally improve the performance of the models, as seen in higher AUC values compared to the Normal and TOMEK-LINKS methods.\n\n3. For binary classification in scenario 1, the experimental analysis recommends the RF model as the most suitable for detecting vaccine type compared to the other models.\n\n4. In scenario 2, the RF, XGBoost, and LGBM models consistently showed good performance across the metrics in all methods, indicating their robustness and effectiveness in classification tasks.\n\n5. The Decision Tree model had relatively lower performance, especially in terms of AUC, in all methods.\n\n6. The results revealed that patient age, gender, allergic history, prior vaccine, other medicines, diabetes, hypertension, and heart disease are significant pre-existing factors that strongly influence the selection of the administered vaccine.\n\nAccording to the study's results, the RF model is recommended for machine learning tasks that demand high accuracy and robustness. While both the XGBoost and LGBM models are also viable options, the RF model could be preferable when dealing with imbalanced data.\n\nThis work can also be applied to any other datasets related to vaccinations. we limited the number of medical history features due to the large dataset size and the computational burden associated with processing each disease. However, further advancements can be made by automating the system to analyze predictions based on more medical history features. As new data is entered into the dataset, the automation can generate new predictions based on the prevailing factors at that particular moment. Furthermore, deep learning models can also be used to extract more hidden patterns to improve COVID-19 vaccine acceptability by better understanding its dynamics.",
"appendix": "Data availability\n\nThe dataset used to support the findings of this study is available at the following: https://vaers.hhs.gov/data/datasets.html.\n\nThe dataset is comprised of three CSV files, namely VAERSDATA, VAERSVAX, and VAERSSYMPTOMS. Within these datasets, VAERSDATA provides comprehensive information regarding individuals, VAERSVAX offers details related to vaccines, encompassing vaccination type, manufacturer, dosage count, and vaccination location, and VAERSSYMPTOMS catalog symptoms reported as various illnesses following vaccinations.\n\n[VAERS Data]: https://vaers.hhs.gov/eSubDownload/index.jsp?fn=2021VAERSDATA.csv.\n\n[VAERS Vaccine]: https://vaers.hhs.gov/eSubDownload/index.jsp?fn=2021VAERSVAX.csv.\n\n[VAERS Symptoms]: https://vaers.hhs.gov/eSubDownload/index.jsp?fn=2021VAERSSYMPTOMS.csv.\n\n\nReferences\n\nVelásquez G: Vaccines, Medicines and COVID-19: How Can WHO Be Given a Stronger Voice? Springer Nature; 2022; 117.\n\nDai X, Xiong Y, Li N, et al.: Vaccine types. Vaccines-the History and Future. IntechOpen; 2019; (pp. 1–18).\n\nEroglu B, Nuwarda RF, Ramzan I, et al.: A Narrative Review of COVID-19 Vaccines. Vaccines. 2021; 10(1): 62. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMonadhel H, Abbas A, Mohammed A: COVID-19 vaccinations and their side effects: a scoping systematic review [version 1; peer review: awaiting peer review]. F1000Res. 2023; 12: 604. Publisher Full Text\n\nVitiello A, Ferrara F: Brief review of the mRNA vaccines COVID-19. Inflammopharmacology. 2021; 29(3): 645–649. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPatel R, Kaki M, Potluri VS, et al.: A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson. Hum. Vaccin. Immunother. 2022; 18(1): 2002083. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAl Khames Aga QA, Alkhaffaf WH, Hatem TH, et al.: Safety of COVID-19 vaccines. J. Med. Virol. 2021; 93(12): 6588–6594. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSujatha R, Venkata Siva Krishna B, Chatterjee JM, et al.: Prediction of suitable candidates for COVID-19 vaccination. Intell. Autom. Soft Comput. 2022; 32(1): 525–541. Publisher Full Text\n\nJavaid M, Haleem A, Singh RP, et al.: Significance of machine learning in healthcare: Features, pillars and applications. Int. J. Intell. Networks. 2022; 3: 58–73. Publisher Full Text\n\nZoumana KEITA: “Classification in Machine Learning: An Introduction”,datacamp.Sep 2022. Reference Source\n\nHatmal MMM, Al-Hatamleh MA, Olaimat AN, et al.: Side effects and perceptions following COVID-19 vaccination in Jordan: a randomized, cross-sectional study implementing machine learning for predicting severity of side effects. Vaccines. 2021; 9(6): 556. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLian AT, Du J, Tang L: Using a machine learning approach to monitor COVID-19 vaccine adverse events (VAE) from twitter data. Vaccines. 2022; 10(1): 103. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVAERS Data Sets: Reference Source\n\nHenry M: Imbalanced Classification in Python: SMOTE-Tomek Links Method.Reference Source\n\nRandom Forest Algorithm: Java T point.2018. Reference Source\n\nDecision Tree Classification Algorithm GeeksforGeeks.08 May, 2023. Reference Source\n\nAbbas AR, Farooq AO: Skin Detection Using Improved ID3 Algorithm. Iraqi J. Sci. 2019; 402–410.\n\nXGBoost ML Model in Python JavaTpoint. http\n\nBanerjee P: LightGBM Classifier in Python Kaggle.2021. Reference Source\n\nNarkhede S: Understanding AUC - ROC Curve Medium.Jun 26, 2018. Reference Source\n\nAbbas AR, Kareem AR: Age estimation using support vector machine. Iraqi J. Sci. 2018; 1746–1756."
}
|
[
{
"id": "257042",
"date": "28 Mar 2024",
"name": "Aritra Ghosh",
"expertise": [
"Reviewer Expertise Data Analysis",
"AI and ML",
"HCI",
"Computational Modeling and Big Data",
"and Web Development. Cuurently working on the application of Machine Learning for COVID-19 vaccine development."
],
"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\nFull Report: Introduction: The introduction provides a comprehensive overview of the transition in vaccine development timelines and the urgent need for effective COVID-19 vaccines. It highlights the significance of understanding vaccine mechanisms and adverse reactions, setting the stage for the proposed machine-learning framework. However, it could benefit from a succinct statement of the study's objectives to guide readers through the subsequent sections more effectively. Literature Review: The literature review effectively contextualizes the study within existing research on machine learning applications in healthcare, specifically focusing on COVID-19 vaccine prediction. It provides insights into relevant studies while emphasizing the novelty and contributions of the current work. However, the review could be strengthened by discussing potential limitations or gaps in previous research, thereby justifying the need for the proposed study more explicitly. Methods: The methods section is detailed and well-structured, outlining the data preprocessing, feature extraction, and modeling techniques employed. It effectively communicates the rationale behind each step and provides clarity on the experimental design. The inclusion of figures and tables enhances the understanding of complex methodologies. However, providing more information on the rationale behind the selection of specific sampling techniques and model evaluation metrics would strengthen the methodology further. Results and Discussion: The results and discussion section presents comprehensive findings from the study, including performance metrics and an analysis of key features. The results are effectively communicated through tables, figures, and textual descriptions, facilitating interpretation. The discussion contextualizes the findings within the broader literature and highlights implications for vaccine selection and adverse reaction prediction. However, a more structured approach to discussing limitations and future research directions would enhance the clarity of the discussion. Conclusion and Future Works: The conclusion summarizes the key findings and implications of the study while outlining potential avenues for future research. It effectively emphasizes the significance of the study's contributions and underscores the importance of continued research in this area. However, providing more specific recommendations for addressing identified limitations and mitigating potential biases would enhance the conclusion's comprehensiveness. Overall Assessment: The abstract and full report provides a detailed and insightful analysis of the proposed machine-learning framework for COVID-19 vaccine prediction. The study demonstrates a rigorous approach to data analysis and model evaluation, yielding valuable insights into vaccine efficacy and adverse reactions. Addressing the following minor issues would further enhance the scientific soundness and readability of the report:\n\nClarity and Readability:\nEnsure consistent terminology throughout the report. For example, use either \"COVID-19 vaccine\" or \"SARS-CoV-2 vaccine\" consistently instead of switching between them. Consider breaking down lengthy paragraphs into shorter ones for easier readability and comprehension, especially in sections like \"Results and Discussion\" and \"Conclusion and Future Works.\" Provide clear transitions between sections to guide the reader through the report more effectively. Each section should flow logically from one to the next.\n\nJustification:\nProvide more justification for the choice of machine learning algorithms. Explain why Random Forest (RF), Decision Tree (DT), Extreme Gradient Boosting (XGB), and Light Grading Boosting Machine (LGBM) were selected over other algorithms. Justify why these algorithms are suitable for the task at hand. Clarify the reasoning behind choosing specific data sampling techniques (e.g., SMOTE, Tomek-links, SMOTETOMEK) to handle imbalanced data. Explain why these techniques were deemed appropriate and how they contribute to improving model performance.\n\nStructure:\nConsider refining the structure of the report to make it more cohesive and organized. For instance, ensure that each section has a clear and specific focus, with subheadings to delineate different topics within the section. Provide a brief overview or summary at the beginning of each section to outline the main points that will be discussed. This will help readers understand the purpose and scope of each section more clearly. In the \"Conclusion and Future Works\" section, provide a concise summary of the key findings and implications of the study. Additionally, offers specific suggestions for future research directions based on the limitations or areas for improvement identified in the study.\n\nBy addressing these minor issues, the report will become more scientifically sound and easier to follow for readers, thereby enhancing its overall quality and impact.\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": "11781",
"date": "23 Aug 2024",
"name": "Hind Monadhel",
"role": "Author Response",
"response": "Dear Aritra Ghosh, Thank you for your valuable feedback and suggestions. We have carefully addressed all your comments and have revised the manuscript accordingly. We appreciate your thorough review and believe the changes have significantly improved the quality of our work. Hind M.Abdullah"
}
]
},
{
"id": "245449",
"date": "03 May 2024",
"name": "Jinran (Ryan) Wu",
"expertise": [
"Reviewer Expertise Machine learning",
"Forecasting",
"Applied Statistics"
],
"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 proposed predicting vaccine types and assessing mortality risk through some ensemble learning approaches. The research topic is interesting, and some comments are given for further consideration. 1. Based on Google Scholar, authors missed citing many recent references that shouldn't be ignored. Here, I suggest using a table to list and compare their main points to highlight your contributions to the area. 2. For the experiment part, all parameter settings are missing, so that the results declared cannot be repeated. Please release your codes or detailed settings in the appendix. 3. For your results, I suggest authors use a cross-validation approach to evaluate the uncertainty of the predictions. 4. Also, considering the imbalance issue, the authors shall consider different penalties for different prediction errors. In other words, we cannot regard \"dies\" as the same as \"non-dies\". Authors shall distinguish different losses. 5. The discussion could have been improved. The authors shall further explore the underlying implications in this part. Otherwise, the work looks like a mathematical game. In particular, the authors shall connect results to some findings from some top medicine journals. 6. The authors shall use a professional writing service to make the content clear.\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": "11782",
"date": "23 Aug 2024",
"name": "Hind Monadhel",
"role": "Author Response",
"response": "Dear Jinran Wu, Thank you for your valuable feedback and suggestions. We have carefully addressed all your comments and revised the manuscript accordingly. Specifically, regarding your suggestion \" 3. For your results, I suggest authors use a cross-validation approach to evaluate the uncertainty of the predictions,\" we will upload the experimental code to ensure clarity. We appreciate your thorough review and believe these revisions have significantly enhanced the quality of our work."
}
]
},
{
"id": "257039",
"date": "25 May 2024",
"name": "Dhamodharavadhani S",
"expertise": [
"Reviewer Expertise Machine learning",
"Predictive Analytics",
"Data Science",
"optimization",
"Big data Analytics"
],
"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, this manuscript makes a significant contribution to the field of healthcare analytics by leveraging machine learning techniques to predict vaccine effectiveness and mortality risk associated with COVID-19 vaccination. The findings have important implications for improving vaccination strategies and patient care. However, I recommend some minor revisions for clarity and precision in language.\nCertainly! Here are some potential review questions for the manuscript:\n1. What are the main objectives of the study, and why are they important in the context of COVID-19 vaccination? 2. How does the study contribute to the existing literature on vaccine effectiveness and adverse reactions? 3. Can you explain the rationale behind selecting ensemble learning algorithms for this study? 4. How were class balancing techniques like SMOTE, TOMEK_LINK, and SMOTETOMEK incorporated into the analysis, and why were they deemed necessary? 5. What were the key factors identified as crucial for predicting vaccine effectiveness and mortality risk? 6. elaborate on the performance metrics used to evaluate the ensemble learning classifiers, and how do they reflect the predictive accuracy of the models? 7. How do the performance outcomes of different ensemble learning algorithms compare in predicting vaccine types and mortality risk? 8. What insights do the findings provide regarding the relationship between pre-existing conditions, medical history, and vaccine outcomes? 9. What practical implications do the study findings have for healthcare practitioners and policymakers? 10. Based on the results obtained, what recommendations would you provide for optimizing COVID-19 vaccination strategies and minimizing adverse reactions? 11. Are there any limitations of the current study that should be addressed in future research?\n\n12. What additional research avenues do you suggest for further advancing our understanding of vaccine effectiveness and safety prediction? 13. In your opinion, how does this study contribute to advancing knowledge in the field of healthcare analytics and COVID-19 vaccination? 19. What are the strengths and weaknesses of the manuscript, and how could they be addressed to enhance its impact and credibility?\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? Yes",
"responses": [
{
"c_id": "11784",
"date": "21 Jun 2024",
"name": "Hind Monadhel",
"role": "Author Response",
"response": "Dear Dhamodharavadhani S, Thank you for your valuable feedback and suggestions. We appreciate your thorough review and believe that these revisions have significantly enhanced the quality of our work."
}
]
},
{
"id": "233060",
"date": "31 May 2024",
"name": "Samir Kumar Bandyopadhyay",
"expertise": [
"Reviewer Expertise Image Processing",
"Forensic Science",
"Machine Learning",
"Crime Science",
"Data Science",
"etc."
],
"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\nAuthors: Q1. Specify the imbalanced dataset with an example. Q2.What type of Illnesses can be seen at the time of vaccination? Q3. Explain EDA since otherwise it is difficult to understand the pre-processing steps. Q4 Pre-existing chronic disease is required to study and it must contain fever nature. Q5.The process of feature extraction is not provided accurately. Q6. What is the difference between attribute values and attribute text? Q7. There are no comparisons with existing methods. Editor: Authors studied to predict which vaccine will be most effective for a candidate without causing severe adverse reactions and to categorize a patient as potentially at high risk of death from the COVID-19 vaccine. In the Feature extraction step, most of the important features in the acquired dataset are presented as textual data. However, in order to analyze them, they must be separated into separate entities. All important parts are not explained properly.\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? 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? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "11783",
"date": "23 Aug 2024",
"name": "Hind Monadhel",
"role": "Author Response",
"response": "Dear Samir, Thank you for dedicating your time and effort to review our manuscript. Your insightful comments and suggestions have provided valuable guidance for improving our work. While we are disappointed by the decision, we genuinely appreciate the constructive feedback that will undoubtedly strengthen our future research efforts. Thank you once again for your thorough review."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1200
|
https://f1000research.com/articles/13-961/v1
|
23 Aug 24
|
{
"type": "Research Article",
"title": "Hybrid Quantum or Purely Classical? Assessing the Utility of Quantum Feature Embeddings",
"authors": [
"J. Simon Richard"
],
"abstract": "Background As graph datasets—including social networks, supply chains, and bioinformatics data—grow in size and complexity, researchers are driven to search for solutions enhancing model efficiency and speed. One avenue that may provide a solution is Quantum Graph Learning (QGL), a subfield of Quantum Machine Learning (QML) that applies machine learning inspired or powered by quantum computing to graph learning tasks.\n\nMethods We reevaluate Quantum Feature Embeddings (QFE), a QGL methodology published by Xu et al. earlier this year. QFE uses Variational Quantum Circuits to preprocess node features and then sends them to a classical Graph Neural Network (GNN), with the goal of increasing performance and/or decreasing total model size. Xu et al. evaluated this methodology by comparing its performance with the performance of variously-sized classical models on the benchmark datasets PROTEINS and ENZYMES, and they report success. Our core methodology and learning task remain unchanged. However, we have made several changes to the experimental design that enhance the rigor of the study: 1) we include the testing of models with no embedder; 2) we conduct a thorough hyperparameter search using a state-of-the-art optimization algorithm; and 3) we conduct stratified five-fold cross-validation, which mitigates the bias produced by our small datasets and provides multiple test statistics from which we can calculate a confidence interval.\n\nResults We produce classical models that perform comparably to QFE and significantly outperform the small classical models used in Xu et al.’s comparison. Notably, many of our classical models achieve this using fewer parameters than the QFE models we trained. Xu et al. do not report their total model sizes.\n\nConclusion Our study sheds doubt on the efficacy of QFE by demonstrating that small, well-tuned classical models can perform just as well as QFE, highlighting the importance of hyperparameter tuning and rigorous experimental design.",
"keywords": [
"Quantum Machine Learning",
"Quantum Graph Learning",
"Graph Neural Networks",
"Quantum Feature Embedding"
],
"content": "1. Introduction\n\nOver the last two decades, a new field at the intersection of quantum computing and machine learning has emerged: Quantum Machine Learning (QML). The methods in this field are best understood when broken down into three categories, as described by Houssein et al.1:\n\n1. Pure QML: algorithms that rely solely on quantum circuits, like the quantum version of the support vector machine,\n\n2. Quantum-inspired ML: classical machine learning that takes inspiration from the field of quantum computing,\n\n3. Quantum-Classical Hybrid ML: techniques that use both quantum computing and classical computing; this includes Variational Quantum Circuits (VQCs) — quantum circuits with classical parameters that can be updated during training using a classical optimizer.\n\nAlgorithms in each of these categories can be applied to a variety of tasks including classification, regression, and optimization.1\n\nWithin QML, an even newer subfield called Quantum Graph Learning (QGL) is starting to be explored. As described by Yu et al.,2 QGL has the potential to solve or mitigate several substantial problems in graph learning including the difficulty of storing and processing large graphs and the limitation of the distance across which inferences can be made. QGL should also be able to apply some of the native benefits of QML to graph learning, including a reduction in the number of required training parameters.\n\nYu et al.2 describe several QML techniques that can be applied to graph learning, including various types of quantum optimization, quantum random walks and quantum graph kernels (used to represent graphs in the vector space of quantum circuits), and VQCs.\n\nThe Quantum Feature Embeddings (QFE) methodology proposed by Xu et al.3 is a special case of the VQC technique. It applies a VQC to the node features of the graph input to generate embeddings, which are then passed to a classical message-passing model (e.g. a Graph Convolutional Network4). This is depicted in Figure 1. (Note that an additional pooling layer has been included. Although this was not mentioned by Xu et al.,3 it is necessary for graph classification.)\n\nXu et al. argue that using a VQC to create embeddings provides several benefits. First, because of the unitary nature of the circuit, the norms of the embeddings are preserved. This preservation helps increase the stability of the model during training. The unitary nature of the VQC also implies that it acts as a bijective function, which means that distinct inputs will not be mapped to the same output. This implies that information will not be lost during the embedding process. Finally, the exponential nature of the circuit’s vector space allows the VQC to approximate complex functions with exponentially fewer trainable parameters compared to classical models.\n\nTo test QFE empirically, Xu et al. evaluated its performance on the classification problems defined by two benchmark datasets: PROTEINS5,6 and ENZYMES.5,7 That performance was then compared with the performance of two classical embedders using Multi-Layer Perceptrons (MLPs). One had D hidden nodes (to approximate the number of parameters in QFE), where D is the number of input features; the other had 2D hidden nodes (to approximate the expressive power of QFE’s vector space). Notably, Xu et al. did not compare QFE with a model with no embedding layer.\n\nTheir results, as depicted in Figure 2, led them to conclude that QFE provides an increased accuracy compared to classical models with similar numbers of parameters and can keep up with classical models that have exponentially more parameters.\n\nNote: The State-Of-The-Art (SOTA) performance on PROTEINS is 85.7%,8 which is much higher than what QFE achieved. However, because QGL and QML in general are young fields, we do not necessarily expect QML models to achieve SOTA performance. Instead, we simply want to determine if the methodology has a positive impact and if it might be useful in the future.\n\nWe critically examine QFE using an improved experimental design with state-of-the-art hyperparameter tuning. This approach yields classical models that perform comparably to QFE and significantly outperform the small classical models used in Xu et al.’s comparison. In addition, we demonstrate that it is possible to obtain similar accuracies with classical models that have fewer trainable parameters.\n\nWhile this paper may not explore new and exciting QML methodologies, it does provide a rigorous evaluation of an existing technique, which is scientifically valuable. Without negative and critical results like this one, it would be impossible to allocate precious research resources efficiently.\n\n\n2. Methods\n\nThe structure of the individual models we tested remains largely unchanged from the methodology created by Xu et al. During inference, node features are taken from the input graph (or batch of graphs) and passed to the embedder component (if it exists). There are five options for the embedder component:\n\n1. No embedder component,\n\n2. MLP-D, a 2-layer perceptron with D input nodes, D hidden nodes and D output nodes,\n\n3. MLP-2D, a 2-layer perceptron with D input nodes, 2D hidden nodes, and D output nodes,\n\n4. QFE-exp, which measures the expectation value of each wire with respect to the Pauli Z gate, and\n\n5. QFE-probs, which measures the probability of each possible output (measured in the computational basis).\n\nThe QFE embedder, a VQC, starts with an angle embedding component using Ry gates (defined below). This component is used to convert the classical node features into a state the quantum computer can process.\n\nIn the entangling component, parameterized Rx gates and controlled not gates (defined below) are combined to create entangling layers which allow the circuit to represent complex functions. The parameters (i.e. the many instances of θ) in these layers are used to update the circuit based on loss calculated between the circuit’s output and the expected output.\n\nThe number of layers used in the entangling component is a hyperparameter of our model. As in Xu et al.’s article,3 we finish with a measuring component that measures all of the wires in the quantum circuit.\n\nFollowing that, the embeddings and the edge connections from the input graph are given to the message-passing model. This model can use any type of message-passing layer (including any one of the 66 convolutional layers provided by the PyTorch Geometric python package9). We chose to test the three layer types chosen by Xu et al.3:\n\n1. Graph Convolutional Network (GCN),4\n\n2. GraphConv,10\n\n3. Graph Attention Transformer (GAT).11\n\nThe number of hidden channels and the number of layers used by the message-passing model are hyperparameters. The number of output channels is equal to the number of classes in the classification problem.\n\nNext, a pooling layer is used to aggregate the data spread across the nodes of the graph being processed. We tested the three simple options below.\n\n1. Mean Pooling\n\n2. Max Pooling\n\n3. Sum Pooling\n\nFinally, a log Softmax function is applied.\n\nDuring initial training runs, we tried both cross-entropy loss, which was used by Xu et al.,3 and Negative Log Likelihood (NLL) loss, which was used in PyTorch Geometric9 examples and in HGP-SL,8 the classical model which achieved the SOTA accuracy on the PROTEINS dataset. Both losses produced similar results; we chose to use NLL loss for its popularity.\n\nTo optimize the parameters of the entire model (including the QFE embedder, when applicable), we used Adam.12\n\nTo mitigate overfitting, we implemented early stopping with a patience of 30 epochs and a maximum training duration of 200 epochs. The metric used for early stopping is the loss taken from the validation dataset. We also employed dropout, the rate of which is a hyperparameter of the model.\n\nFor each embedder option, we optimized our hyperparameters by running a multi-objective Optuna13 study that used the Non-dominated Sorting Genetic Algorithm II (NSGA-II) algorithm.14 Each study included approximately 200 experiments. Their objectives were to …\n\n• maximize average validation accuracy,\n\n• minimize the variability of the validation accuracy (based on a 95% confidence interval),\n\n• minimize the number of trainable parameters.\n\nThe hyperparameters we optimized are listed below.\n\n• The number of QFE layers (if applicable)\n\n• The message passing layer type\n\n• The number of layers and hidden channels in the message-passing model\n\n• The dropout rate\n\n• The Adam optimizer’s learning rate and weight decay\n\nWe also optimized the batch size during our initial experiments. However, since this hyperparameter was shown to have low importance (using the fANOVA evaluation method15) and since the varying memory usage it caused made it difficult to run experiments in parallel, we ultimately chose to hold it constant at 1024.\n\nTo increase the stability of each experiment within the Optuna13 study and obtain an estimate of variability, we performed stratifiedfive-fold cross-validation on the provided training dataset and then bootstrapped the accuracies to obtain a 95% confidence interval.\n\nStratified five-fold cross-validation was conducted on the entire dataset to control for the bias caused by our train/test data split and to provide multiple test accuracies which could be used to estimate the variability of the test statistic.\n\nFor each of the train/test data splits provided by cross-validation and for each embedder option, we ran hyperparameter tuning and then selected three of the best models produced, each maximizing one of the utility functions below.\n\nTo decrease the storage and maintenance burden during hyperparameter tuning and because each model only took a few minutes to train [2], we chose not to save model weights. Instead, we retrained each of the selected models after tuning, this time using a stratified shuffle split to divide the training dataset into a training dataset and a validation dataset (for use during early stopping). To decrease the non-deterministic effects of our training script on the results, we also implemented a minimum training duration of 60 epochs. If early stopping was triggered before then (which likely indicates that training had failed to produce a well-performing model), then the model would be retrained. This could happen up to five times before the training script progresses to the next model.\n\nFinally, we evaluated the selected models from each fold on their corresponding test dataset and then used bootstrapping to calculate a 95% confidence interval for the mean test accuracy.\n\n\n3. Experiments\n\nTo evaluate our models, we used the same two protein-related graph datasets used by Xu et al.3: PROTEINS5,6 and ENZYMES.5,7 Both of these datasets are a part of the TUDataset collection16 and are publicly available on http://www.graphlearning.io.\n\nThe graphs contained in these datasets represent the structures of proteins, and the nodes within these graphs represent secondary protein structures — helixes, sheets, and turns. Two nodes are connected “if they are neighbors along the amino acid sequence or one of three nearest neighbors in space”.16 In addition to the secondary structure type, which is represented in the dataset using one-hot encoding, nodes have feature(s) representing some of the structure’s physical and/or chemical properties. The PROTEINS dataset has one such feature; the ENZYMES dataset has 18. Because our computer could not simulate the 21 qubits (three one-hot encoded categories + 18 additional features) that would be required for the ENZYMES dataset, we used Principal Component Analysis (PCA) to reduce the node features back down to four dimensions. Despite this large reduction, the resulting features explain 99.3% of the variance in the original features.\n\nIn PROTEINS, proteins are classified as enzymatic or non-enzymatic. In ENZYMES, proteins (which are all enzymatic) are classified according to the class of the reaction they catalyze; there are six such classes. For both of these datasets, our goal is to predict the graph-level classifications based on the nodes’ features and graph’s structure as a whole.\n\nBoth datasets are quite small; PROTEINS contains 1113 graphs and ENZYMES contains 600. And the graphs in both datasets are mid-sized; in PROTEINS, they have an average of 39.06 nodes and 72.82 edges, and in ENZYMES, the have an average of 32.63 nodes and 62.14 edges. A few examples from PROTEINS and ENZYMES are depicted in Figures 3 and 4 respectively.\n\n\n4. Results and Discussion\n\nThis section focuses on notable examples from and visual representations of our results. Our complete results data, optimized hyperparameters, model weights, and code have been published on Zenodo17 under the Creative Commons Attribution 4.0 International Public License (CC BY 4.0). Our code is also available on GitHub at https://github.com/jsimonrichard/QFE-Experiments under the MIT License.\n\nUsing UBest Accuracy, we found models with average test accuracies on the PROTEINS dataset ranging from 0.68 to 0.72. In particular, we achieved an average accuracy of 0.68 using the QFE-probs embedder and an average accuracy of 0.71 using the QFE-exp embedder, both of which are comparable to the results achieved by Xu et al.3 However, we also achieved an average accuracy of 0.71 using the MLP-D embedder and an average accuracy of 0.72 using no embedder, which are comparable to the QFE accuracies and significantly higher than the MLP-D accuracies produced by Xu et al.3\n\nThe average sizes of our models range from 111K to 320K trainable parameters. Notably, the average number of trainable parameters used by our MLP-D-based models is lower than the average for our QFE-based-models (but not significantly lower) even though it exceeds their average accuracies. The results for all five embedder types are depicted with error bars (α=0.05) in Figure 5.\n\nUnfortunately, Xu et al. did not report their models’ total sizes, so we cannot make direct size comparisons between our models and theirs. They did report the number of floating-point operations (FLOPS) required for MLP-2D embedder to process a graph with 40 nodes and the quantum gate operations required for their QFE embedder to process a graph of the same size.3,18 However, these metrics are not relevant to our analysis since the sizes of the embedders are overshadowed by the variance in the sizes of the message-passing layers.\n\nThe models found using UBestAll performed almost as well as those found with UBest Accuracy, but with an order of magnitude fewer parameters. They achieve accuracies ranging from 0.68 to 0.71 with average parameter counts ranging from 13K to 43K. Their results are depicted in Figure 6.\n\nFinally, we found models using ULowParameters that maintain that performance with even fewer parameters. Their average accuracies range from 0.69 to 0.72 and their average sizes range from 3K to 11K trainable parameters. Notably, this includes the models using MLP-2D, which maintain an average accuracy of 0.69 using an average of 3K trainable parameters. The results for all five embedder types are shown in Figure 7.\n\nOur results from ENZYMES represent an even more drastic departure from the results reported by Xu et al. In fact, every single average taken from the models using MLP-D or no embedder is significantly greater than the highest MLP-D accuracy that Xu et al. achieved [3].\n\nThe models found using UBest Accuracy achieve average accuracies ranging from 0.32 to 0.46 with average parameter counts ranging from 124K to 299K. Notably, the models with no embedder achieved the highest average accuracy (0.46) with an average of 269K trainable parameters. This average is significantly greater than all of the accuracies reported by Xu et al. The results for all five embedders are depicted in Figure 8.\n\nAgain, most of the models found using UBestAll achieve similar average accuracies (although the highest average is no longer 0.46) using an order of magnitude fewer parameters. Their average accuracies range from 0.26 to 0.35 and their average parameter counts range from 18K to 46K. These results are shown in Figure 9.\n\nFinally, the models found by ULowParameters achieve similar results with marginally fewer parameters for some and essentially the same number of parameters for others. They achieve accuracies ranging from 0.27 to 0.40 with sizes ranging from 3K to 48K trainable parameters. These results are shown in Figure 10.\n\n\n5. Conclusion\n\nOur analysis sheds doubt on QFE’s efficacy in the real world despite its interesting mathematical foundations. Using the same datasets as Xu et al.,3 we achieved similar and, in some cases, significantly better performance compared to the accuracies reported by Xu et al.3 using models with QFE, models with the MLP-D embedder, and models with no embedder at all. In addition, we showed that it is possible to find classical models with comparable performance that have fewer trainable parameters than their quantum-classical hybrid counterparts. Why did Xu et al. fail to reach these conclusions? There may have been a few contributing factors.\n\n• They overlooked classical models with no external embedder.\n\n• They probably did not use the same hyperparameter tuning method we did (they make no mention of their tuning methods in3).\n\nIn addition, they did not provide error bars, so it is hard to know whether their results are statistically significant.\n\nOur study highlights the critical importance of careful experimental design, statistical testing, and thorough hyperparameter tuning. Without these things, it is difficult if not impossible to draw sound conclusions in a rapidly evolving field like QGL.\n\nThere are several limitations (and corresponding future research directions) to this study.\n\n• Because of the small sizes of both the PROTEINS and ENZYMES datasets, it is difficult to show statistically significant differences. We were able to do so in a few cases, but most comparisons that could be made are insignificant. Future research may include evaluating QFE on larger datasets.\n\n• It is still unclear why QFE is failing to provide an advantage in either accuracy or model size. One possibility is that the QFE embedder does not have much information to work with because it only operates on individual node features, which are fairly one-dimensional (in both PROTEINS and ENZYMES, the first component generated by PCA explains over 95% of the variance). QFE may still be useful in other contexts.\n\n\nImplementation details\n\nOur code can be found on GitHub: https://github.com/jsimonrichard/QFE-Experiments. The main libraries we used are listed below; thanks go out to all of their authors and maintainers.\n\n• Classical NN Framework: PyTorch19\n\n• Quantum Framework: Pennylane20\n\n• Dataset Management and Prebuilt Classical Models: PyTorch Geometric9\n\n• Cross-Validation: scikit-learn21\n\n• Stats Calculations: SciPy22\n\n• Hyperparameter Tuning: Optuna13\n\nIn addition, our training script was largely inspired by the training script written for HGP-SL16 (located at https://github.com/cszhangzhen/HGP-SL).",
"appendix": "Data availability statement\n\nOur complete results data, optimized hyperparameters, model weights, and code have been published on Zenodo with the title “Trained models, code, result data, and Optuna study data from ‘Hybrid quantum or purely classical? Assessing the utility of quantum feature embeddings.’” 17 doi: 10.5281/zenodo.13117645 under the Creative Commons Attribution 4.0 International Public License (CC BY 4.0). Our code is also available on GitHub at https://github.com/jsimonrichard/QFE-Experiments under the MIT License.\n\n\n\n1. ENZYMES: http://www.graphlearning.io/ ; publicly available, but attribution is required (see https://chrsmrrs.github.io/datasets/docs/home/ )\n\n2. PROTEINS: http://www.graphlearning.io/ ; publicly available, but attribution is required (see https://chrsmrrs.github.io/datasets/docs/home/ )\n\n\nAcknowledgments\n\nThis paper is the primary product of J. Simon Richard’s undergraduate Honors Thesis for the Washkewicz College of Engineering at Cleveland State University. Thank you to the Washkewicz College of Engineering for its support.\n\nIn addition, thank you to Sascha Xu, a current PhD student at the CISPA Helmholtz Center for Information Security and the corresponding author of Xu et al.’s article, 3 for his quick email responses and for his willingness to help.\n\nFinally, we acknowledge that AI—specifically Anthropic’s Claude 3.5 Sonnet model—was used to help draft and/or improve the phrasing of a few sections in this paper: the abstract, section 1.2, and the last paragraph of section 5. Each of those sections have been reviewed and edited thoroughly for clarity and correctness by the human author of this paper.\n\n\nReferences\n\nHoussein EH, Abohashima Z, Elhoseny M, et al.: Machine learning in the quantum realm: The state-of-the-art, challenges, and future vision. Expert Syst. Appl. May 2022; 194: 116512. Publisher Full Text\n\nYu S, Peng C, Wang Y, et al.: Quantum Graph Learning: Frontiers and Outlook.Feb. 02, 2023. arXiv: arXiv:2302.00892. Publisher Full Text\n\nXu S, Wilhelm-Mauch F, Maass W: Quantum Feature Embeddings for Graph Neural Networks. Proceedings of the 57th Hawaii International Conference on System Sciences. , Jan. 2024. Accessed: Jan. 20, 2024. Reference Source\n\nKipf TN, Welling M: Semi-Supervised Classification with Graph Convolutional Networks.Feb. 22, 2017. arXiv: arXiv:1609.02907. Publisher Full Text\n\nBorgwardt K, Ong CS, Schönauer S, et al.: Protein Function Prediction via Graph Kernels. Bioinforma. Oxf. Engl. Jul. 2005; 21 Suppl 1: i47–i56. PubMed Abstract | Publisher Full Text\n\nDobson PD, Doig AJ: Distinguishing Enzyme Structures from Non-enzymes Without Alignments. J. Mol. Biol. Jul. 2003; 330(4): 771–783. PubMed Abstract | Publisher Full Text\n\nSchomburg I, et al.: BRENDA, the enzyme database: updates and major new developments. Nucleic Acids Res. Jan. 2004; 32(suppl_1): 431D–4433D. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang Z, et al.: Hierarchical Multi-View Graph Pooling With Structure Learning. IEEE Trans. Knowl. Data Eng. Jan. 2023; 35(1): 1–559. Publisher Full Text\n\nFey M, Lenssen JE: Fast graph representation learning with PyTorch Geometric. ICLR workshop on representation learning on graphs and manifolds. 2019.\n\nMorris C, et al.: Weisfeiler and Leman Go Neural: Higher-order Graph Neural Networks.Nov. 30, 2021. arXiv: arXiv:1810.02244. Publisher Full Text\n\nVeličković P, Cucurull G, Casanova A, et al.: Graph Attention Networks.Feb. 04, 2018. arXiv: arXiv:1710.10903. Publisher Full Text\n\nKingma DP, Ba J: Adam: A Method for Stochastic Optimization.Jan. 29, 2017. arXiv: arXiv:1412.6980. Publisher Full Text\n\nAkiba T, Sano S, Yanase T, et al.: Optuna: A Next-generation Hyperparameter Optimization Framework. Proceedings of the 25th ACM SIGKDD International Conference on Knowledge Discovery & Data Mining, in KDD’19. New York, NY, USA: Association for Computing Machinery; Jul. 2019; pp. 2623–2631. Publisher Full Text\n\nDeb K, Pratap A, Agarwal S, et al.: A fast and elitist multiobjective genetic algorithm: NSGA-II. IEEE Trans. Evol. Comput. Apr. 2002; 6(2): 182–197. Publisher Full Text\n\nHutter F, Hoos H, Leyton-Brown K: An Efficient Approach for Assessing Hyperparameter Importance. Proceedings of the 31st International Conference on Machine Learning. PMLR; Jan. 2014; pp. 754–762. Accessed: Jul. 08, 2024. Reference Source\n\nMorris C, Kriege NM, Bause F, et al.: TUDataset: A collection of benchmark datasets for learning with graphs.Jul. 16, 2020. arXiv: arXiv:2007.08663. Publisher Full Text\n\nRichard JS: Trained models, code, result data, and Optuna study data from ‘Hybrid quantum or purely classical? Assessing the utility of quantum feature embeddings.’. Zenodo. Jul. 30, 2024. Publisher Full Text\n\nXu S: Private Correspondence.Jul. 11, 2024.\n\nPaszke A, et al.: PyTorch: an imperative style, high-performance deep learning library. Proceedings of the 33rd International Conference on Neural Information Processing Systems. Red Hook, NY, USA: Curran Associates Inc.; 2019; pp. 8026–8037.\n\nBergholm V, et al.: PennyLane: Automatic differentiation of hybrid quantum-classical computations.Jul. 29, 2022. arXiv: arXiv:1811.04968. Publisher Full Text\n\nPedregosa F, et al.: Scikit-learn: Machine Learning in Python. J. Mach. Learn. Res. 2011; 12(85): 2825–2830.\n\nVirtanen P, et al.: SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods. Mar. 2020; 17(3): 261–272. PubMed Abstract | Publisher Full Text | Free Full Text\n\n\nFootnotes\n\n1 We chose to use z-scores because they are simple, scale-independent, and less affected by outliers compared to min-max normalization. However, it is important to note that the underlying distributions are not normal, so we cannot use these scores to analyze the experiment distributions directly.\n\n2 On our machine—a Linux PC with an AMD Ryzen Threadripper 1920X CPU and an Nvidia RTX 2080 Ti GPU—the quantum-classical hybrid models took an average of 8 minutes to train on PROTEINS and an average of 3 minutes and 18 seconds to train on ENZYMES. The purely classical models took an average of 1 minute and 14 seconds to train on PROTEINS and an average of 1 minute and 25 seconds to train on ENZYMES.\n\n3 Xu et al. did not report the raw data for their ENZYMES results, so we took them from their results plot (Figure 2) using https://plotdigitizer.com/app. The values we measured can be found in our Zenodo repository. 17"
}
|
[
{
"id": "317287",
"date": "18 Sep 2024",
"name": "Yunpu Ma",
"expertise": [
"Reviewer Expertise Quantum Machine Learning",
"Temporal and dynamic graphs"
],
"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 proposes a method to evaluate the efficacy of an existing algorithm, quantum feature embedding (QFE).\nStrengths: 1. The experimental methodology is described with clarity and is easy to follow. 2. The comparative results across different experimental settings are clearly presented in the form of well-structured plots. 3. The figure illustrating the QFE concept is visually clear and aids understanding.\nWeaknesses: 1. VQC as a bijective function: In the introduction, the authors claim that a variational quantum circuit (VQC) is a bijective function. This is clearly differentiated from what is described in the QFE paper. Could the authors elaborate on specific cases in which a VQC would be considered bijective?\n2. Novelty and contribution: The primary contribution of the paper, as stated by the authors, is the repetition and evaluation of QFE without proposing a new methodology. The paper, as a result, feels more like a detailed subsection on experimental setup rather than a complete study. To strengthen the novelty, I suggest comparing various QFE approaches within the same evaluation framework and considering additional datasets for comparison. The current results could also serve as a baseline for the development of new QFE methods.\n3. Use of baseline points: Some of the baseline points for comparison are derived from a plotting tool rather than directly from the original data. This diminishes the reliability and persuasiveness of the comparison results. Using actual numerical values from the data would improve the robustness of the evaluation.\n4. I would recommend to cite the works of QFE for graphs: Ma Y, et al, 2021,[Ref 1[and Ma Y et al, 2019 .[Ref 2]\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "327443",
"date": "11 Oct 2024",
"name": "Jun Qi",
"expertise": [
"Reviewer Expertise quantum machine learning",
"machine learning",
"quantum computing"
],
"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 this work, the author proposes a quantum feature embedding method combined with a graph neural network for real-world applications on Protein and Enzyme datasets. The theory and experiments are well-written and suitable for indexing.\n\nThere are several major concerns about this work.\n\n1. The author leverages quantum circuits to extract feature embeddings, which are combined with classical graph neural networks. It is unclear why the quantum feature embeddings can be meaningful for classical methods.\n\n2. Other quantum machine learning methods have been proposed for quantum embeddings, like using quantum convolutional neural networks and quantum kernel learning. It is necessary to compare the proposed quantum feature embeddings with the existing ones.\n\n[1] Yang, C.H.H., Qi, J., Chen, S.Y.C., Chen, P.Y., Siniscalchi, S.M., Ma, X. and Lee, C.H., Decentralizing feature extraction with quantum convolutional neural network for automatic speech recognition. In IEEE International Conference on Acoustics, Speech and Signal Processing, pp. 6523-6527, 2021 [Ref - 1].\n[2] Schuld, M., 2021 [Ref - 2]. Supervised quantum machine learning models are kernel methods. arXiv preprint arXiv:2101.11020.\n3. When the author mentions the hybrid quantum-classical neural networks, several recent works are recommended to be cited.\n\n[1] Liu, J., Liu, M., Liu, J.P., Ye, Z., Wang, Y., Alexeev, Y., Eisert, J. and Jiang, L., 2024 [Ref - 3]. Towards provably efficient quantum algorithms for large-scale machine-learning models. Nature Communications, 15(1), p.434.\n\n[2] Qi, J., Yang, C.H.H., Chen, P.Y. and Hsieh, M.H., 2023 [Ref - 4]. Theoretical error performance analysis for variational quantum circuit based functional regression. npj Quantum Information, 9(1), p.4.\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/13-961
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https://f1000research.com/articles/13-960/v1
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23 Aug 24
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{
"type": "Research Article",
"title": "Identifying factors influencing faculty attitude towards digital technology in higher education and its impact on faculty engagement and work performance: a mediating analysis",
"authors": [
"Sanyukta Chhibber",
"Babita Rawat",
"Dhani Shanker Chaubey",
"Richa Khugshal",
"Dhani Shanker Chaubey",
"Richa Khugshal"
],
"abstract": "Background This study investigated the influence of various factors on Faculty Attitude, Faculty Engagement, and Work Performance in higher education. The study specifically examined the impact of faculty attitudes towards digital technology on their level of involvement and effectiveness in the classroom. Furthermore, it investigated how the utilization of digital technology by faculty members influences the connection between their attitudes and job performance.\n\nMethods The study utilized a mixed-methods approach, combining quantitative and qualitative methodologies to collect thorough data to explore the factors influencing faculty attitude. A survey was performed among 438 faculty members from higher educational institutions in the Delhi and NCR region.\n\nResults The results indicated a strong positive relationship of perceived usefulness, mutual learning, institutional support, collaborativeness, creativity, critical thinking, and faculty attitude towards digital technology adoption in academic setting. Nevertheless, External Pressure did not exhibit a significant relationship. The study revealed that the attitude of faculty members has a significant impact on both their work performance and engagement. Additionally, faculty engagement was found to have a positive impact on work performance. The mediation Analysis revealed that Faculty Engagement served as a partial mediator in the association between Faculty Attitude and Work Performance.\n\nConclusions The study’s implications underscore the urgent need of fostering positive attitudes and engagement among faculty members for enhancing their performance in academic settings. Some of the limitations and implication of the study and future direction of the research directions are suggested.",
"keywords": [
"Faculty Attitude",
"Digital Technology",
"Higher Education",
"Faculty Engagement",
"Work Performance"
],
"content": "Introduction\n\nIn today’s rapidly evolving educational landscape, the integration of digital technology within higher education institutions has become increasingly prevalent. The adoption of digital technology in higher education requires a multifaceted approach that considers the interplay of various drivers influencing faculty attitudes. Faculty perspectives and behaviour regarding technology integration are influenced by a variety of factors including external pressure, perceived usefulness, mutual learning, technological competency, institutional support, communication and collaboration, as well as creativity and critical thinking. To effectively encourage the use and exploitation of digital technology in teaching and learning, institutions must give priority to these drivers through strategic planning, professional development activities, and supportive policies.\n\nIn India, digital technology is drastically changing higher education and how educators and students interact. Digital tools are now essential to the educational process due to the widespread availability of smartphones, tablets, and high-speed internet access. Many courses and resources are available to students nationwide, no matter where they live, thanks to platforms like Moodle, Coursera, and Khan Academy. An important move towards digital learning platforms is predicted in the Indian online education sector, which is predicted to reach $1.96 billion by 2021, according to a report by the National Association of Software and Service Companies (NASSCOM, 2021). Moreover, programs such as the National Digital Library of India (NDLI) facilitate access to an extensive collection of scholarly materials, thereby advancing educational democratization.\n\nAccording to Choudhury and Kar (2020), digital technology not only improves accessibility but also creates interactive and collaborative learning environments that equip students for the needs of the digital age. But issues like the digital divide and the requirement for faculty training in technology integration still exist, calling for coordinated actions to guarantee fair access to and efficient use of digital resources in higher education. As noted by Rogers (2000) faculty attitudes play a crucial role in the adoption and integration of new technologies within educational settings. Research by (Picciano, 2021) emphasizes the necessity of aligning faculty beliefs and perceptions with technological advancements to enhance student learning experiences. Educational institutions offer online education to enhance access, generate revenue, and cater to internet-savvy students (Bacow et al., 2012). However, faculty development in online teaching lags behind demand (Lloyd, 2013). Cooperation from all faculty, not just early adopters, is crucial for accommodating this growth (Hiltz et al., 2007). More research is requiredto determine the hurdles to online instruction (Shea, 2007), as faculty motivation substantially impacts student success (Hiltz et al., 2007).\n\nAccording to Singh et al. (2023); Kumar and Lauermann (2018), Indian faculty members are reluctant to adopt digital technology in the classroom. This resistance prevents widespread adoption despite its potential advantages because of doubts about its efficacy (Sharma et al., 2018) and worries about a lack of training (Chahar et al., 2021). Furthermore, faculty resistance to or enthusiasm for digital tools can greatly impact their degree of involvement and overall efficacy in teaching (Bates, 2015). Thus, it is crucial to investigate and address staff attitudes toward digital technology in order to create a favourable learning atmosphere and encourage ongoing academic performance development. This study aims to investigate the factors that impact faculty attitudes toward digital technology in the classroom and how those attitudes affect teacher engagement and productivity in higher education. The study also looks at how faculty use of digital technology influences the relationship between faculty attitude and work performances. The researcher was motivated to select faculty members affiliated with higher education organizations in the Delhi NCR region for the planned study due to their accessibility.\n\nThis research explores the intricate interactions that shape academics’ perspectives on the use of digital technology in higher education. According to Hannafin et al. (2014), institutions and faculty are forced to integrate digital tools into their research and teaching due to external forces such as global educational trends and technological improvements. Perceived usefulness, a fundamental component of the Technology Acceptance Model (TAM), highlights people’s opinions about how valuable digital technology is for improving teaching methods (Davis, 1989). Teachers working together to learn collaboratively makes it easier to share ideas and accelerates the adoption of digital innovations (Fini et al., 2018).\n\nFaculty members’ ability to use digital tools effectively is demonstrated by their technological competency, which is a crucial aspect (Al Lily and Alhazmi, 2019). Faculty use of digital technology is heavily influenced by institutional support, which includes leadership, resources, and policy (Browne et al., 2000). Digital platforms improve communication and collaboration among faculty members, improving their connectedness and information sharing. This creates an atmosphere that is favourable for the incorporation of technology (Veletsianos & Kimmons, 2012). Additionally, creativity and critical thinking highlight the transformative potential of digital tools in enhancing teaching and learning experiences (Ogawa et al., 2020; Sharma & Barrett, 2008). This study aims to shed light on how digital technology deployment affects faculty engagement and work performance in higher education by analysing the interactions between these variables. Technological proficiency emerges as a critical factor, reflecting faculty members’ competence in utilizing digital tools effectively (Al Lily and Alhazmi, 2019). Institutional support, encompassing policies, resources, and leadership, significantly influences faculty engagement with digital technology (Browne et al., 2000). Communication and collaboration facilitated by digital platforms enhance faculty connectivity and knowledge sharing, fostering a conducive environment for technology integration (Veletsianos & Kimmons, 2012). Moreover, creativity and critical thinking underscore the transformative potential of digital tools in enriching teaching and learning experiences (Ogawa et al., 2020; Sharma & Barrett, 2008). By examining the interplay of these factors, this study seeks to illuminate the impact of digital technology adoption on faculty engagement and work performance in higher education.\n\nDigital technology integration is becoming more important in today’s quickly changing educational environment. But there are a number of elements that affect how faculty members at higher education institutions use these technologies. The purpose of this review is to examine the literature on the factors influencing faculty attitudes regarding the use of digital technology. Specifically, we will look at factors like institutional support, perceived utility, mutual learning, technological competency, external pressure, interpersonal and teamwork, creativity, and critical thinking.\n\nFaculty attitudes towards technology adoption are significantly influenced by perceived usefulness, as articulated by the Technology Acceptance Model (TAM) (Davis, 1989). It measures how much a person believes a system improves job performance and is a crucial component of the Technology Acceptance Model (Davis, 1989). This concept, which evaluates technology’s usefulness, supports consumers’ acceptance of it (Davis, 1989). According to (Al Lily, 2014), faculty members in higher education are more willing to adopt digital technology when they believe it would improve student outcomes, increase efficiency and improve their teaching techniques. If faculty members believe digital technology will improve their ability to educate, engage students, and produce quality learning outcomes, they are more likely to adopt it (Venkatesh et al., 2003). Furthermore, perceived usefulness is increased when technological elements and educational objectives line up (Ngai et al., 2007). These arguments result in the following hypothesis being assumed.\n\nPerceived Usefulness has a significant influence on faculty attitude toward the adoption of digital technology in higher educational programs.\n\nAccording to Ally and Samaka (2013), mutual learning is the cooperative sharing of information and experiences about integrating digital technologies among faculty members. Communities of practice, professional development seminars, and peer exchanges promote reciprocal learning and change teachers’ perspectives on embracing technology (Rogers et al., 2016). Faculty participation in collaborative learning initiatives promotes a culture of creativity and digital tool experimentation (Dabbagh & Kitsantas, 2012). Peer-to-peer learning possibilities also impact faculty members’ openness to digital technology. Research has shown that implementing collaborative professional development and knowledge-sharing activities can cultivate a positive attitude towardadopting technology (Graham et al., 2019). Educators can exchange optimal methodologies, tackle difficulties, and collaboratively enhance their comfort level with digital resources by participating in cooperative learning activities. The following assumptions are made as a result of these arguments.\n\nMutual learning motives have significant influence on faculty attitude towards adoption of digital technology in higher educational programs.\n\nInstitutional support includes resources, infrastructure, and organizational policies that help faculty members use technology (Brown, 2015). An atmosphere favorable for technological integration can be created with the help of technical support, sufficient finance, and supportive leadership (Educause, 2020). Faculty attitudes toward the use of digital technology in higher education are greatly influenced by their perceptions of institutional support (Koh & Lim, 2012). Academic opinions toward the deployment of digital technology are significantly influenced by institutional support (Dahlstrom & Bichsel, 2014). Technology integration is seen favorably when sufficient infrastructure, resources, and support systems are in place. When faculty see strong institutional support for their projects, they are more inclined to adopt digital tools. The following assumptions are made as a result of these arguments.\n\nInstitutional support significantly influences faculty attitudes toward the adoption of digital technology in higher educational programs.\n\nWhen faculty members are under pressure to incorporate digital technology into their teaching techniques, this is referred to as external pressure. Examples of external stakeholders include administrators, legislators, and accrediting organizations. Studies reveal that faculty attitudes toward the deployment of technology are greatly impacted by outside pressure (Jones & Dexter, 2014). According to Verhoef et al. (2019), institutions should embrace digital transformation because of changing consumer behavior, more digital competition, and technological advancements. Depending on the level of support given, faculty members may view outside pressure as coercive, which increases resistance, or as a catalyst for change (Christensen et al., 2015). Various factors, such as institutional requirements, shifting educational environments, and social expectations, might cause this pressure (Alam, 2017). Faculty members’ attitudes towards adoption may be shaped by their obligation to incorporate digital tools and technology to comply with these outside demands. These arguments result in the following hypothesis being assumed.\n\nExternal Pressure significantly influences faculty attitudes toward the adoption of digital technology in higher educational programs.\n\nCreating an atmosphere that encourages the adoption of digital technologies within academic institutions requires effective communication and collaboration (Bates, 2015). Higher education’s increased accessibility to devices has encouraged students to use collaborative platforms like Google Docs, Wikis, and Forums more often. Despite increased security concerns, cloud computing tools—such as Google Drive and Dropbox—are more user-friendly and therefore favoured for resource sharing than Learning Management Systems (LMS). Social media and online meeting platforms also facilitate collaboration, though institutional, educational, and cultural impediments get in the way (Biasutti, 2017; Manca & Ranieri, 2016; Martin & Parker, 2014; Stantchev et al., 2014; Veletsianos, 2012). Effective communication and collaboration channels are essential for increasing faculty participation in technology adoption programs (Preston & Hylton, 2010). Collaborative efforts between academics, instructional designers, and IT professionals produce creative digital learning experiences, and open feedback loops and conversations foster a communal feeling of ownership (Bates & Sangrà, 2011; Bower et al., 2017). The following assumptions are made as a result of these arguments.\n\nCollaborativeness significantly influences faculty attitudes toward the adoption of digital technology in higher educational programs.\n\nFaculty views on adopting digital technology are significantly influenced by their creativity and critical thinking, which highlight the tools’ transformative potential in improving the teaching and learning processes (Johnson et al., 2013). Another important factor influencing faculty attitudes is incorporating digital technology to foster creativity and critical thinking (Jang & Kim, 2017). Teachers who view digital tools as engines for creative instruction and improved student participation are more inclined to integrate technology into their teaching strategies. Academics that value creativity and critical thinking methods are more likely to investigate cutting-edge teaching techniques made possible by digital technology (Henriksen et al., 2016).\n\nStudent engagement, autonomy, and problem-solving skills are strengthened when creative and critical thinking skills are included in technology-assisted learning environments (Zurita & Nussbaum, 2004). These argumentsled to the assumption of the following hypothesis\n\nCreativity and critical thinking significantly influence faculty attitudes toward adopting digital technology in higher educational programs.\n\nFaculty members’ adoption of digital technology has grown increasingly crucial within the academic domain, bearing substantial consequences for both professional performance and instructional strategies. Scholars like (Jones et al., 2022) have emphasized how digital tools may improve teaching methods and create more engaging learning environments. Furthermore, studies by Brown et al. (2020), who clarified the beneficial effects of technology on scholarly productivity and collaboration within academic communities, have emphasized the incorporation of digital platforms into research endeavors. Despite these advantages, faculty members’ views of digital technology vary from eager acceptance to fearful opposition. Several reasons exist for this opinion difference, including technological competence, age differences, and institutional support networks (Johnson et al., 2016). Furthermore, it is important to seriously consider how technology can worsen inequality and alienate particular student groups (Selwyn, 2019). Therefore, it is essential to have a comprehensive grasp of faculty attitudes regarding digital technology in order to develop strategies that will both fully utilize its potential and minimize any associated obstacles within the academic setting. These arguments led to the assumption of the following hypothesis.\n\nFaculty attitude toward digital technology in academics has a positive and significant effect on their work performance.\n\nEmployee engagement at work is greatly influenced by faculty attitudes towards digital technology (Liao & Li, 2020). Matar et al. (2020) found a positive correlation between positive perceptions of technology and higher levels of commitment and job satisfaction. On the other hand, unfavorable viewpoints could prevent participation and discourage the use of technology (Teng & Wang, 2021). This study investigates the effect of professors’ views towards digital tools on their involvement and output in the classroom.\n\nWhile (Al Lily et al., 2013) draw attention to the connection between faculty attitudes towards technology and institutional effectiveness (Rienties & Kinchin, 2014), emphasized the significance of faculty acceptance for successful technology integration. Academics who use digital technologies in their instruction frequently demonstrate increased motivation and inventiveness (Xu & Jaggars, 2011). Therefore, increasing faculty engagement and boosting educational outcomes need a supportive environment promoting positive attitudes toward technology (Nguyen & Nguyen, 2019). These arguments led to the assumption of the following hypothesis\n\nFaculty attitude toward digital technology in academics has a positive and significant effect on their engagement in digital technology.\n\nScholars have thoroughly studied the effects of adopting digital technologies on research and teaching effectiveness. The transformative potential of digital technologies in supporting creative instructional approaches and boosting student involvement was highlighted by Newsome et al. (2021). Furthermore, Brown et al. (2020) clarified how digital platforms might expedite administrative work, increasing faculty productivity. Furthermore, research Lee et al. (2019) demonstrated the association between faculty members’ professional competency and digital literacy. However, as noted by Johnson (2021), there are still issues, such as the digital gap in education and technological impediments that prevent effective integration into academic procedures.\n\nTherefore, cultivating a positive learning and working environment requires a comprehensive understanding of faculty involvement with digital technology. Future research endeavors should explore techniques for increasing digital literacy and alleviating associated obstacles to maximize the potential benefits for teachers and students. These arguments led to the assumption of the following hypothesis.\n\nFaculty Engagement with digital technology in academics hasa positive and significant influence on their work performance.\n\nFaculty Engagement with digital technology in academics mediates the relationship between faculty attitude and their work performance.\n\nThe relationship between technology adoption, faculty attitudes, engagement, and work performance in higher education settings forms the basis of the conceptual framework of the present study. This study examines how perceived utility and simplicity of use affect users’ attitudes toward adopting technology. It draws on Davis’s (1989) Technology Acceptance Model (TAM), which states that these elements affect users’ attitudes toward technology adoption. The study also looks at how faculty attitudes about digital technology are shaped by these characteristics. Additionally, it looks at the function that faculty engagement plays as a mediator in the relationship between the views of faculty members towards digital technology and their productivity at work, as suggested by Fredricks et al. (2004).\n\nBy merging various theoretical frameworks, the study will shed light on the intricate relationships between faculty attitudes, technology adoption, engagement, and work performance in higher education. The Unified Theory of Acceptance and Use of Technology (UTAUT) by Venkatesh et al. (2003) is another source the study uses, considering the impact of variables like behavioral intention, enabling conditions, and social influence. In order to determine the mediating role of engagement in the relationship between attitudes towards digital technology and work performance, a Mediating Analysis—inspired by Baron and Kenny (1986)—will be used to understand the complex relationships between faculty attitudes, engagement, and work performance.\n\nThe study attempts to integrate these theoretical foundations to provide a thorough knowledge of the complex interactions between faculty perspectives, technology adoption, and professional outcomes in the field of higher education. The following model was proposed for the present study.\n\n\nMethods\n\nThe present research work is based on primary and secondary data. A descriptive research design was employed in this study. Research work encompasses a comprehensive approach to understand the complex relationship between faculty attitudes toward digital technology, their engagement, and work performance within higher education, as depicted in Figure 1. The methodology integrates quantitative and qualitative techniques to gather data, allowing for a nuanced exploration of the factors influencing faculty attitudes. (Al Lily et al., 2018, 2024; Dabbagh & Kitsantas, 2012; Dabbagh & Kitsantas, 2012; Davis, 1989; Dahlstrom et al., 2015; Fredricks et al., 2004; Jones & Dexter, 2014; Wu et al., 2020; Manca & Ranieri, 2016; Rogers et al., 2016; Teng & Wang, 2021; Verhoef et al., 2019; Venkatesh et al., 2003).\n\nSource: Author’s Compilation.\n\nThe statement was further modified as the study context and objectives. The initial draft of the questionnaire was validated with the help of faculty, researcher scholars, and industry professionals. After the questionnaire was validated, a pilot test was conducted on 25 respondents at different educational institutes in Delhi and the NCR region. An initial reliability test using the Cronbach alpha(α) test was carried out, and the values werefound to be 0.855. After assuring reliability, a full-scale survey was conducted, adopting online and line survey methods. The questionnaire was fed in Google Docs and sent to respondents, who requested to pass it on to their known ones. Initially, the questionnaire was sent to 200 respondents, and it was sent to other target populations. The researcher got 460 responses. After editing, 438 responses were found to fit and were considered for analysis. SPSS software and PLS-SEM 4.0 (Licensed version) were used for data analysis. Mediation analysis was employed to examine the mediating role of faculty engagement in the relationship between attitudes toward digital technology and work performance. By adopting this methodological approach, the study aims to contribute to the existing literature on technology adoption in academia and provide practical insights for enhancing faculty productivity and effectiveness. Table 1 indicates the demographic characteristics of respondents.\n\nThe demographic characteristics of the respondents are presented in Table 1. The distribution of respondents by age shows that the majority fall within the age range of 26-35 years (38.6%), followed by those aged 36-50 years (23.7%), while the least represented group comprises individuals above 60 years (6.8%). In terms of gender, male respondents constitute a larger proportion (61.6%) compared to females (38.4%). Regarding education level, the majority hold postgraduate degrees (61.6%), with a smaller percentage possessing Ph.D. degrees (36.1%), while graduates represent a minority (2.3%). Designation-wise, the highest frequency is observed among researchers (34.2%), followed by assistant professors (26.0%), with professors being the least represented (10.7%). Regarding experience, respondents with 4-6 years of experience constitute the largest group (24.4%), followed closely by those with more than 15 years of experience (8.4%). In contrast, those with up to 3 years of experience form the smallest group (21.5%).\n\nThe descriptive statistics from Table 2 provide insights into factors influencing faculty adoption of digital technology and its impact on faculty engagement and work performance in academia. On average, faculty members perceive digital technology as useful (M = 3.3280, SD = 0.79996) and essential for modern education (M = 3.5868, SD = 1.06559). Institutional support is moderately high, with faculty reporting sufficient training and technical assistance (M = 3.8887, SD = 0.93512). External pressures, such as accreditation requirements and industry expectations, also influence technology adoption (M = 3.9886, SD = 0.82709). Collaborative aspects of technology are generally positive, though concerns about isolation exist (M = 3.7922, SD = 0.82991). Faculty attitude towards technology is generally favorable, with a belief in its ability to enhance education (M = 3.4041, SD = 0.62213). Additionally, technology adoption positively impacts work performance, productivity, and stress management (M = 3.7363, SD = 0.49881). Despite challenges in keeping up with technological advancements, faculty recognize its benefits in improving teaching quality and fostering critical thinking (M = 3.8219, SD = 0.71613). Overall, these findings underscore the multifaceted nature of faculty attitudes regarding digital technology integration in academia, with implications for both pedagogy and professional development initiatives.\n\nThe study employed PLS SEM modeling to investigate factors influencing the adoption of digital technology, focusing on faculty attitude, Faculty Engagement and Work Performance. The reliability and validity of constructs were assessed through Cronbach’s alpha, composite reliability (rho_a and rho_c), and average variance extracted (AVE). Table 3 shows that constructs exhibited acceptable levels of internal consistency, with Cronbach’s alpha ranging from 0.781 to 0.961. Composite reliability values (rho_a and rho_c) exceeded the minimum threshold of 0.7, indicating good reliability, with values ranging from 0.864 to 5.225 and 0.836 to 0.968, respectively. Additionally, AVE values ranged from 0.642 to 0.910, surpassing the minimum acceptable threshold of 0.5, signifying satisfactory convergent validity. Notably, construct reliability and validity were demonstrated across all factors, underscoring the robustness of the measurement model in assessing faculty attitudes, towards digital technology adoption, faculty engagement and work performance.\n\nThe discriminant validity of constructs was assessed using the heterotrait-monotrait ratio (HTMT) in Table 4. The HTMT values indicate the extent to which constructs are distinct from each other. Generally, HTMT values below 0.85 are considered indicative of discriminant validity. Results revealed that all constructs exhibited discriminant validity, with HTMT values ranging from 0.036 to 0.247. For instance, Collaborativeness demonstrated the lowest HTMT value of 0.036 when compared to Mutual Learning, indicating a clear distinction between these constructs. Similarly, Faculty Engagement and Faculty Attitude showed a relatively low HTMT value of 0.053, further confirming discriminant validity. Notably, the highest HTMT value was observed between Faculty Engagement and Work Performance (0.982), which still falls well below the threshold, affirming the distinctiveness of these constructs. These findings underscore the adequacy of discriminant validity among the measured constructs, as none of the HTMT values exceed the recommended threshold of 0.85, thus providing confidence in the construct validity of the measurement model.\n\nThe discriminant validity of the constructs was assessed using the Fornell-Larcker criterion (Fornell & Larcker, 1981). As depicted in Table 5, the diagonal values represent the square roots of the Average Variance Extracted (AVE) for each construct, while the off-diagonal values indicate the correlations between constructs. According to the criterion, the square root of the AVE for each construct should exceed the inter-construct correlations to establish discriminant validity. In this study, all diagonal values exceeded the corresponding off-diagonal values, suggesting adequate discriminant validity (Fornell & Larcker, 1981). Specifically, the diagonal values ranged from 0.801 to 0.915, exceeding the inter-construct correlations, which ranged from -0.244 to 0.934. These findings provide evidence that each construct captures unique variance beyond the overlap with other constructs, thus supporting the discriminant validity of the measurement model (Fornell & Larcker, 1981).\n\nThe structural model was analyzed through hypothesis testing, incorporating statistical values and assessing significance levels. With a minimum acceptable threshold set at p < 0.05, the model’s parameters were evaluated for their impact on the observed data. The hypothesis testing procedure aimed to determine whether the proposed relationships within the structural model were statistically significant. Statistical values, including beta coefficients and p-values, were utilized to ascertain the strength and direction of these relationships. The analysis revealed significant relationships among the variables. Faculty Engagement demonstrated the highest explanatory power for Work Performance, with an R-square of 0.898. Conversely, Faculty Attitude had a relatively weaker association, explaining 14.9% of the variance in Work Performance. Collaborativeness, Creativity and Critical Thinking, and External Pressure showed minimal contributions, with respective f-square values of 0.028, 0.042, and 0.021, falling below the minimum acceptable threshold.\n\nThe structural model as shown in Table 6 was employed to investigate the relationships between various factors and their impact on Faculty Attitude, Work Performance, and Faculty Engagement within an academic setting. The analysis revealed significant path coefficients for Perceived Usefulness (β = 0.176, t = 4.110, p < 0.001), Mutual Learning (β = 0.170, t = 4.195, p < 0.001), Institutional Support (β = 0.169, t = 2.294, p = 0.022), Collaborativeness (β = 0.155, t = 3.881, p < 0.001), and Creativity and Critical Thinking (β = 0.191, t = 4.561, p < 0.001), indicating their significant positive influence on Faculty Attitude. However, External Pressure did not exhibit a significant relationship (β = 0.140, t = 1.379, p = 0.168). Moreover, Faculty Attitude demonstrated strong positive effects on both Work Performance (β = 0.603, t = 15.515, p < 0.001) and Faculty Engagement (β = 0.900, t = 101.453, p < 0.001). Additionally, Faculty Engagement positively impacted Work Performance (β = 0.368, t = 9.353, p < 0.001). Furthermore, the indirect effect of Faculty Attitude on Work Performance through Faculty Engagement was also significant (β = 0.331, t = 9.053, p < 0.001). These findings suggest that fostering perceptions of usefulness, mutual learning, institutional support, collaborativeness, and creativity and critical thinking among faculty members can enhance their attitudes, which in turn positively influence both their engagement and performance within the academic environment.\n\nThe structural model analysis revealed significant path coefficients indicating relationships between faculty attitude, faculty engagement, and work performance, as depicted in Figure 2 Faculty attitude significantly predicted work performance (β = 0.603, t = 15.515, p < 0.001), demonstrating that a positive attitude among faculty members positively impacts their work performance. Moreover, faculty attitude strongly influenced faculty engagement (β = 0.900, t = 101.453, p < 0.001), highlighting the critical role of attitude in fostering engagement within academic settings. Additionally, faculty engagement was found to significantly predict work performance (β = 0.368, t = 9.353, p < 0.001), emphasizing the importance of engagement for enhancing work performance. Furthermore, the mediation analysis revealed that faculty engagement partially mediated the relationship between faculty attitude and work performance, with a significant indirect effect (β = 0.331, t = 9.053, p < 0.001). These findings underscore the significance of both faculty attitude and engagement in shaping faculty members’ work performance, with engagement playing a mediating role in the relationship between attitude and performance.\n\nSource: Author’s Compilation.\n\nThis research was conducted in accordance with the guidelines of the Research Ethics Board (REB) of Uttaranchal University. The Research Ethics Board has given the approval on June 11, 2024, and the approval number is UU/DRI/EC/2024/005.\n\nThe questionnaire has been submitted to REB of the university, and the board members and chairperson have identified the viability of the research topic. All the authors presented their research objectives to the board then the questionnaire got approval to conduct the study.\n\nThe consent from all the participants involved in the study has been taken. A self-explanatory written statement was attached with the questionnaire for the participants and a similar questionnaire has been submitted to the university research board (REB).\n\n\nDiscussion\n\nThis study delves into the complex relationship among various factors affecting Faculty Attitude, Faculty Engagement and Work Performance, within the academic setting. Using structural model analysis, the research identifies significant influences of factors such as Perceived Usefulness, Mutual Learning, Institutional Support, Collaborative Ness, and Creativity and Critical Thinking on Faculty Attitude. Furthermore, it explores the mediating role of Faculty Engagement in the correlation between Faculty Attitude and Work Performance.\n\nIn academia, the effectiveness of faculty members is pivotal for upholding the standards of education and research. Our finding reveals that faculty attitude has a positive effect on faculty engagement and work performance. Presentresearch finding is in conformance with the previous research work of Offorbike, S. A., Nnadi, C. S. O., & Agu, J. C. (2018) and Rahiman, M H U & Kodikal, (2017) who indicated that Attitude positively impacts job performance and they are positively correlated to each other. Understanding the determinants of faculty attitude, engagement, and subsequent performance is indispensable for institutions striving to enhance their overall efficacy. This study endeavors to elucidate these connections through a structural model analysis.\n\nThe purpose of the present study was to analyse how faculty attitudes towards the adoption of digital technologies affected their work engagement. The results show that these attitudes are positively correlated. Previous studies highlight the significance of multiple factors in influencing faculty involvement, performance, and attitude. It is noteworthy that studies show a positive correlation between faculty attitude and the perceived utility of activities and resources (Smith et al., 2018). Furthermore, there is a correlation between increased faculty involvement and satisfaction and supportive institutional settings and collaboration (Chang & Fisher, 2019; Jones & George, 2020). Furthermore, it has been shown that faculty members who foster their creativity and critical thinking are more productive researchers and teachers (Robinson & Stern, 2017). The results of this investigation align with earlier studies conducted by Sang., Wang., Li., Xi., & Yang (2023), highlighting the importance of elements such as perceived utility, institutional support, and cooperation in cultivating favourable attitudes and involvement among academic staff (Jones & George, 2020; Smith et al., 2018). Additionally, mediation analysis highlights the critical role that faculty engagement plays in transforming positive attitudes into improved job performance. Nowadays, it is critical to integrate digital technology, which calls for a thorough grasp of the variables affecting faculty attitudes towards its adoption and ensuing work engagement. The mediator function of faculty engagement, which acts as a vital conduit between faculty attitudes towards the use of digital technologies and their general job engagement, is at the centre of this conversation. According to Van (2020), faculty engagement refers to teaching staff members’ active participation in and dedication to their tasks and responsibilities in the classroom. Not only does this involvement affect how they view digital technology, but it also determines how excited and committed they are to their work.\n\nAdditionally, research done by Maier et al. (2020) emphasises the importance of faculty engagement as a mediator in understanding attitudes towards technology adoption and work engagement, stressing the critical role that faculty engagement plays in determining the efficacy and success of digital integration initiatives in higher education. As a result, acknowledging and encouraging faculty involvement becomes an essential tactic for improving attitudes regarding the adoption of digital technology as well as faculty members’ subsequent work engagement, which in turn creates a more inventive and favourable academic climate. These results imply that creating collaborative, encouraging cultures that support faculty members’ creativity and critical thinking should be a top priority for educational institutions. These kinds of programmes are essential to raising general performance and involvement in educational environments staff (Jones & George, 2020; Smith et al., 2018).\n\nThe theoretical understanding of the variables influencing faculty engagement, work performance, and attitude in academic settings is improved by this research. Through the use of a structural model, the study explores the relationships between various elements and how they affect these key concepts. First, the study outlines a number of significant variables that affect faculty attitude. Interestingly, and in line with earlier studies (Jones & Ismail, 2018; Smith et al., 2017), perceived usefulness, mutual learning, institutional support, collaborativeness, and creativity and critical thinking all stand out as important drivers. Furthermore, the study highlights the strong positive impact that faculty attitudes have on work performance and faculty engagement. This result is consistent with other research showing that positively oriented faculty members promote job satisfaction and enhanced performance (Aziz et al., 2019; Wang & Netemeyer, 2020). Moreover, the research underscores the significant influence of Faculty Attitude on Faculty Engagement, stressing the critical function of optimistic perspectives in fostering engagement in academic settings (Choi & Moon, 2021).\n\nThe study’s practical implications highlight how critical it is that academic institutions address the variables affecting teacher involvement and performance (Cochran-Smith et al., 2020). Enhancing perceived utility and mutual learning through programmes like training courses and interdisciplinary collaboration are important tactics that come from the findings (A. R. Jones et al., 2019). Faculty happiness and productivity are greatly enhanced by institutional support systems, such as mentorship programmes and collaborative workspaces (Tabarés Gutiérrez et al., 2020). Johnson (2017) asserts that innovative teaching and research require faculty members to be encouraged to be creative and to think critically. Furthermore, highlighting the value of an engaged and positive faculty can improve overall performance and institutional achievement (Robinson & Johnson, 2021). Academic organisations may establish encouraging settings that promote faculty professional development and institutional advancement by putting these research-based tactics into practice (Lynch et al., 2022).\n\n\nConclusion\n\nTo sum up, a structural model was utilised in the study to investigate the connections among different elements and how they affect faculty engagement, work performance and attitude in an academic environment. The results showed that perceived utility, peer learning, institutional support, teamwork, creativity, and critical thinking all had a substantial beneficial impact on faculty attitudes. Consequently, there was a high correlation between faculty engagement and work performance and attitude. Faculty Attitude and Work Performance are somewhat mediated by Faculty Engagement, which has a beneficial impact on Work Performance. These findings are consistent with earlier studies highlighting the significance of attitudes and engagement in academic contexts (Jones et al., 2020; Smith, 2018) and imply that encouraging positive perceptions and attitudes among faculty members can improve their engagement and performance within academia.\n\nIn an academic setting, the study looked at the effects of several factors on faculty engagement, work performance, and attitudes. Relationships between faculty attitude, collaborativeness, creativity, and critical thinking, mutual learning, perceived usefulness, and institutional support were found to be significantly beneficial. A substantial link was not shown by External Pressure, though. Work performance was positively impacted by faculty engagement as well as by faculty attitude, which both significantly influenced each other. According to a mediation analysis, there is a partial mediating effect of faculty engagement between work performance and faculty attitude. For faculty members to perform better in academic environments, the study emphasizes the value of encouraging positive attitudes and participation. The study’s context-specific design may restrict its generalizability, and other research is necessary to examine other factors impacting teacher attitudes and participation.\n\n\nEthical statement\n\nThis research was conducted in accordance with the guidelines of the Research Ethics Board (REB) of Uttaranchal University. The Research Ethics Board has given the approval on June 11, 2024, and the approval number is UU/DRI/EC/2024/005.\n\nThe questionnaire has been submitted to REB of the university, and the board members and chairperson have identified the viability of the research topic. All the authors presented their research objectives to the board then the questionnaire got approval to conduct the study.\n\n\nInformed consent\n\nThe consent from all the participants involved in the study has been taken. A self-explanatory written statement was attached with the questionnaire for the participants and a similar questionnaire has been submitted to the university research board (REB).",
"appendix": "Data availability\n\nThe underlying data related to the paper are available in figshare with the following citation and DOI.\n\nFigshare: datasheet_Identifying Factors Influencing Faculty Attitude towards Digital Technology in Higher Education and its Impact on Faculty Engagement and Work Performance A Mediating Analysis, Sanyukta Chhibber, DOI: https://doi.org/10.6084/m9.figshare.25959421.v1 (Chhibber et al., 2024).\n\nThe data available were submitted by Sanyukta Chibber Licensed under CC BY 4.0. complete details are- Identifying Factors Influencing Faculty Attitude towards Digital Technology in Higher Education and its Impact on Faculty Engagement and Work Performance: A Mediating Analysis © 2024 by Sanyukta Chibber, Babita Rawat, Babita Rawat, Richa Khugshal is licensed under CC BY 4.0\n\nAll the data was collected from the respondents by filling out the questionnaire and can be made public in SPSS file format if required.\n\n\nReferences\n\nAlam MR: Factors influencing faculty members’ adoption of technology in higher education. 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}
|
[
{
"id": "317267",
"date": "09 Sep 2024",
"name": "Dirgha Raj Joshi",
"expertise": [
"Reviewer Expertise Applied mathematics",
"educational technology and digital pedagogy"
],
"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\nDear Editor, Thank you for this opportunity to review this paper. The study examined the impact of faculty attitudes towards digital technology on their level of involvement and effectiveness in the classroom. The paper is good and indexed. The research contributes appropriate knowledge in the field of educational technology focusing professional carrier of the higher education teacher.\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": "329436",
"date": "29 Oct 2024",
"name": "Harisa Mardiana",
"expertise": [
"Reviewer Expertise Educational Technology",
"Digital Competence",
"Digital Literacy",
"Learning outcomes",
"Teaching online",
"Mixed-method."
],
"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 no. 2 1. Structure and Flow Clarify Key Themes Early On\nThe introduction starts with a broad focus, but you can emphasize more strongly why faculty attitudes are crucial. Consider stating from the outset that faculty attitudes are a key determinant of the success of digital technology integration in higher education.\nConsider adding a transition sentence that connects the global context to the specific case of India.\nClarity and Specificity Elaborate on Drivers of Attitude When you mention the drivers of faculty attitudes (e.g., perceived usefulness, mutual learning, technological competency), it would help to briefly explain each one to add clarity to their relevance. You mention them quickly and move on without unpacking their significance.\nAvoid Redundancy\nSome sentences repeat similar information or are redundant. For example: \"Digital technology is drastically changing higher education...\" followed by \"Digital tools are now essential to the educational process...\"—these could be merged for conciseness.\nProvide More Recent Data You reference NASSCOM’s report, which predicts the online education market to reach $1.96 billion by 2021. Since we are now past 2021, you should either update this data or remove it. If there is no recent data, you could phrase it more generally: The online education sector has grown rapidly in recent years...\nLiterature Integration Diverse Citations You do a good job of integrating various studies, but ensure all citations are formatted consistently. For instance, Research by (Picciano, 2021) should be rephrased to follow a consistent style: According to Picciano (2021)...\nAddress the Gaps in Literature The literature cited should be linked to the gap your study aims to address. You've mentioned that faculty attitudes are important, but also briefly touch on other studies that discuss the need for more research (e.g., Shea, 2007; Lloyd, 2013). Explicitly state how your study contributes to filling these gaps.\n\nCoherent Conclusion The last part of the introduction where you explain why the Delhi NCR region was selected is slightly abrupt. You could provide more reasoning as to why this region, in particular, provides a valuable context for studying digital technology adoption (e.g., its level of technological advancement, access to digital resources, or institutional diversity).\nReview of related literature Introduction to the Review Clarify Scope and Focus The opening paragraph is somewhat vague and shows insufficient clarity regarding the overall purpose of the literature review. Strengthen the introduction by explicitly stating the aim of reviewing specific factors in relation to faculty attitudes and the significance of addressing this topic in the current educational landscape.\nMinor Rephrasing Instead of “there are a number of elements that affect how faculty members use these technologies”, consider using more precise language: “multiple factors influence faculty members’ adoption and integration of digital technologies in higher education.”\n2. Perceived Usefulness Repetition of Sources and Ideas The section on Perceived Usefulness is slightly repetitive, as you reference the Technology Acceptance Model (TAM) and Davis (1989) multiple times without introducing new insights. Consider streamlining these references into a single, cohesive statement.\nRelevance to Hypothesis The connection between perceived usefulness and your hypothesis is clear, but consider briefly justifying why this factor is particularly important in higher education. For instance, emphasize how aligning educational goals with technology impacts long-term digital adoption.\nMutual Learning Clarify the Concept The concept of mutual learning could be explained more thoroughly. Instead of jumping straight into the literature, briefly introduce the idea that mutual learning involves collaborative knowledge-sharing and how it plays a role in influencing faculty attitudes.\nSupportive Citations The section uses good references, but the citation format could be improved. For example, instead of \"Research has shown...\" without a direct reference, use a clearer citation structure: Research by Graham et al. (2019) has shown that collaborative professional development enhances faculty openness to digital technology.\nInstitutional Support Expansion of Institutional Support The section on institutional support could be expanded to include more specific examples of how this factor influences faculty attitudes. For instance, elaborate on what types of institutional resources (e.g., training programs, technical infrastructure) are critical for promoting a positive attitude toward digital technology. Cite More Recent Studies While the citations are generally relevant, consider incorporating more recent studies, especially in the context of rapid technological advancements in education since 2020. For example, you could reference how the COVID-19 pandemic accelerated digital technology adoption in higher education and led to new institutional support mechanisms.\nGeneral Improvements Consistency in Citations Ensure consistent citation formatting throughout. For example, Dabbagh & Kitsantas (2012) should follow a consistent pattern with the rest of the citations (e.g., using \"and\" instead of \"&\" when citing within the text).\nAddress Gaps Highlight any gaps in the literature. For example, is there limited research on mutual learning in specific educational contexts like India? This would provide a justification for your research and demonstrate how your study contributes to the field.\nMethodology 1. Research Design Clarity: Descriptive Research Design\nYou mention that a descriptive research design was employed, but this statement is vague and doesn't clearly communicate how the design fits the study's aims. Provide more detail on why a descriptive design was chosen and how it aligns with your research objectives.\n2. Primary and Secondary Data Specify Secondary Data Usage You mention that the research is based on both primary and secondary data, but there is no mention of how the secondary data was used in the analysis. Clarify the sources of secondary data and its role in the study, or remove this reference if only primary data was analyzed.\n3. Citation Formatting and Relevance Correct Repetitive Citations You have some repetitive citations in the first paragraph (e.g., Dabbagh & Kitsantas, 2012 appears twice). Make sure that citations are unique and relevant. Additionally, remove references that do not directly contribute to the methodology explanation.\n4. Questionnaire Validation More Detail on Validation Process The section about the validation of the questionnaire is brief. You could provide more details on how the validation was conducted, what kind of feedback was received, and how the questionnaire was modified in response.\n\n5. Survey Methods Specify the Distribution and Sampling Strategy You mention that the questionnaire was distributed via Google Docs and that respondents were asked to pass it on to others. This method may introduce sampling bias. Clarify how the survey was distributed, the response rate, and any measures taken to ensure a representative sample.\n6. Results of Pilot Test Clarify the Pilot Test Findings You mention that the pilot test was conducted with 25 respondents and a Cronbach's alpha of 0.855 was found, which suggests reliability. However, you could briefly explain the significance of this value and any modifications made to the questionnaire based on pilot testing.\n\nRephrase for Conciseness: In places, the wording could be more concise. For example, “The statement was further modified as the study context and objectives” can be rephrased to: “The questionnaire was refined to align with the study's context and objectives.”\n\nDiscussion Sentence Structure & Flow Some sentences are long and complex, which may affect readability. Try to break them into simpler, shorter sentences. For example, in the sentence \"The results showed that perceived utility, peer learning, institutional support, teamwork, creativity, and critical thinking all had a substantial beneficial impact on faculty attitudes,\" consider splitting it for better readability.\nCohesion Between Concepts While you effectively highlight the relationships between factors, some transitions between ideas could be smoother. For example, when discussing creativity and institutional support, you might want to briefly tie these to the broader theme of digital technology adoption in education. This would help reinforce the relevance of each factor within the main research question.\nReferencing Check for repeated references. For example, you reference \"Jones & George, 2020; Smith et al., 2018\" several times. Ensure there’s no redundancy and clarify any similar studies that are cited multiple times. Additionally, you cited \"Van (2020)\"—please ensure this is referenced correctly with full details in your bibliography\nClarifying the Role of the Mediation Analysis The section on mediation analysis is essential but could be expanded for clarity. You briefly mention that faculty engagement mediates between attitudes and work performance, but you can elaborate on the statistical significance or theoretical implications of this mediation for a deeper understanding.\nTheoretical Contribution This section is strong, but you can tie it back to specific theories in educational technology or faculty performance to underline how your work builds on these frameworks. For instance, connecting the faculty attitudes and engagement more explicitly with well-known theories (such as Ajzen's Theory of Planned Behavior, if applicable) could help position your findings within a broader theoretical context.\nRepetitive Phrasing The phrase \"critical thinking and creativity\" appears multiple times. You could vary the language or combine similar ideas to avoid redundancy.\nFuture Research Directions: The \"Limitations and Future Scope\" section mentions the context-specific design may limit generalizability, but it could be more specific. Suggesting specific populations, geographical contexts, or alternative methodologies for future research will strengthen this section.\nEthical Statement & Data Availability This section is solid. However, you might want to add a brief explanation of how the ethics approval ensures compliance with general research integrity standards.\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/13-960
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https://f1000research.com/articles/13-956/v1
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23 Aug 24
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{
"type": "Study Protocol",
"title": "Novel gastrointestinal tools (GI Tools) for evaluating gut functional capacity in adults with environmental enteropathy in Zambia and Zimbabwe: A cross-sectional study protocol",
"authors": [
"Tracy N. Phiri",
"James W. Weatherill",
"Elena Monford-Sanchez",
"Jose-Ivan Serrano-Contreras",
"Callum Melvin",
"Mirriam Kunaka",
"Ian Chisenga",
"Perpetual Ngalande",
"Monica N. Mweetwa",
"Ellen Besa",
"Tafhima Haider",
"Nilanjan Mandal",
"Alex J. Thompson",
"Christine A. Edwards",
"Claire D. Bourke",
"Ruairi C. Robertson",
"Joram M. Posma",
"Rosemary Banda",
"Mulima Mwiinga",
"Lydia Kazhila",
"Leolin Katsidzira",
"Mutsa Bwakura-Dangarembizi",
"Beatrice Amadi",
"Isabel Garcia-Perez",
"Kathryn Maitland",
"Julian R. Marchesi",
"Douglas J. Morrison",
"Gary Frost",
"Paul Kelly",
"Tracy N. Phiri",
"James W. Weatherill",
"Elena Monford-Sanchez",
"Jose-Ivan Serrano-Contreras",
"Callum Melvin",
"Mirriam Kunaka",
"Ian Chisenga",
"Perpetual Ngalande",
"Monica N. Mweetwa",
"Ellen Besa",
"Tafhima Haider",
"Nilanjan Mandal",
"Alex J. Thompson",
"Christine A. Edwards",
"Claire D. Bourke",
"Ruairi C. Robertson",
"Joram M. Posma",
"Rosemary Banda",
"Mulima Mwiinga",
"Lydia Kazhila",
"Leolin Katsidzira",
"Mutsa Bwakura-Dangarembizi",
"Beatrice Amadi",
"Isabel Garcia-Perez",
"Kathryn Maitland",
"Julian R. Marchesi",
"Douglas J. Morrison",
"Gary Frost"
],
"abstract": "Background Environmental enteropathy (EE) is a highly prevalent subclinical inflammatory intestinal disorder associated with growth failure, impaired neurocognitive development, poor response to oral vaccines, and micronutrient deficiencies. However, EE research and clinical trials are hampered by the lack of non-invasive tools for measuring intestinal function in detail. This study aims to develop new tools for the measurement of multiple domains of gut functional capacity.\n\nMethods The GI TOOLS project is a cross-sectional study that will recruit adults aged 18-65 years with EE in Lusaka, Zambia. Each participant will undergo assessment of gut functional capacity using novel near-point-of-care tools and provide multiple samples for detailed laboratory analyses. Participants will also undergo endoscopy for collection of duodenal biopsies. Novel techniques include stable isotopes approaches to measuring digestion, absorption, and bidirectional transmucosal amino acid flux, a non-invasive fluorescence tool for real-time evaluation of gut permeability, and assessment of reverse permeation of intravenous antibiotics to be carried out separately in Zimbabwe. Stool and duodenal microbiome sequencing using MinION sequencing, metabolome analysis applied to plasma and intestinal fluids, blood immune cell phenotyping, in vitro epithelial barrier models, and duodenal immunohistochemistry will also be used to explore EE in depth. These will all be integrated with gold standard histology and mucosal morphometry, alongside lactulose permeation data, and stool and plasma biomarker analysis. The protocol has been approved by ethics committees and regulators in Zambia, Zimbabwe, and the UK. Participants will give informed consent before they can participate\n\nAnticipated outcomes Based on this extensive phenotyping, tests will be developed which can be simplified and refined for use in adults and children with EE, and for clinical trials. Findings from this project will be disseminated through in-person meetings with caregivers and regulatory bodies, presentations at conferences and in peer-reviewed journals.",
"keywords": [
"Environmental Enteric Dysfunction",
"Intestinal Absorption",
"Intestinal Permeability",
"Microbiome",
"Stable Isotopes"
],
"content": "Introduction\n\nThe gastrointestinal tract is a critical organ, simultaneously orchestrating digestion, absorption, and excretion of gut contents whilst providing a physical barrier between the external environment in the gut lumen and body tissues, creating conditions to tolerate dietary antigens and the gut microbiome.1 However, measurement of these intestinal functions, which we refer to hereafter as gut functional capacity, is currently crude and imprecise. There is an urgent need to develop improved tools for the evaluation of a broader range of intestinal functions in studies of pathophysiology and clinical trials in both adults and children.1 Following a golden age of research on human intestinal digestion and absorption in the 1970s and 1980s, work on gut physiology has slowed. Current gold-standard approaches to assess gut functional capacity, such as the lactulose-mannitol (or lactulose-rhamnose) test or endoscopy, are time- and labour-intensive or measure only one aspect of intestinal dysfunction, such as its permeability to molecules which normally are excluded from uptake in the healthy state.\n\nEnvironmental enteropathy (EE) is a highly prevalent subclinical inflammatory intestinal disorder that is associated with exposure to unsanitary conditions and poor nutrition. In children, it is associated with growth failure, impaired neurocognitive development, and poor response to oral vaccines. EE is frequently associated with undernutrition. In moderate undernutrition, limited nutrient bioavailability, pathogen pressure, and gut barrier dysfunction can lead to impaired linear growth (stunting), impaired vaccine response and cognitive deficits in children.2 In acute undernutrition, mortality remains unacceptably high, particularly those hospitalised with severe acute malnutrition (SAM).3,4 Both stunting and incomplete recovery from SAM in childhood embed life-long and intergenerational health consequences which detrimentally impact population and economic health in low- and middle-income countries (LMICs).5–7\n\nEE probably represents a chronic adaptation of the proximal small intestine to marginal diets and exposure to environmental enteropathogens.8 In LMICs, this adaptation develops in early life and is characterised by reduced absorptive surface area, goblet and Paneth cell depletion and intraepithelial lymphocyte infiltration.9 Our work indicates that SAM is associated with a more severe enteropathy10; a global disturbance of intestinal architecture and function, including maldigestion, malabsorption and impaired gut barrier function.13 Impaired gut barrier function allows translocation of microbes and their products, which may explain systemic endotoxemia and, in some cases, sepsis and septic shock, which are major drivers of mortality.11–13 Both SAM and the antibiotic treatments recommended for children admitted to hospital with SAM also affect the gut microbiome, the composition of which is associated with lower bacterial diversity and maturity, which fail to persistently recover with standard nutritional therapies.14 There is a need to take a holistic approach to understanding the impact of undernutrition and EE on gut physiology across the whole gastrointestinal tract, which means developing tools for assessing multiple domains15 of gut function (Figure 1). This necessitates simultaneous assessment of the structure of the intestine (e.g. villus height, and therefore surface area), barrier function and microbial translocation, digestive and absorptive capacity (e.g., enzyme activity for protein, fat, and carbohydrate digestion, transporter expression for absorption), systemic, and intestinal immune responses to pathogens, expression of epithelial pattern recognition receptors (PRRs), pathogen-associated molecular patterns (PAMP; an indicator of microbial translocation), and the composition, function and metabolic activity of the gut microbiota. The latter will be reflected in the measured host metabolome. Such measurements will allow the selection of an optimised ‘toolkit’ for assessing gut functional capacity and ultimately enable the design of novel therapeutic feeds, which actively promote improved gut function, support sustained rehabilitation, reduce mortality, and feed the superorganism (i.e., the host and microbiome), and not just the host. Recent evidence has demonstrated that designing a diet to enhance normal maturation of the colonic microbiota results in improved growth14,16,17 versus standard therapies in children recovering from acute malnutrition. Probiotic interventions have the potential to improve recovery and growth in various malnutrition disorders,18 providing the proof-of-principle that rational design of feeds or biotherapeutics targeted to support gut function could be an achievable and effective therapeutic approach at scale.\n\nIllustration of prominent elements of inflammation cycle, that includes (i) changes to gut microbiota diversity and pathobiome colonisation leading to decompartmentalization, which promotes (ii) epithelial barrier failure leading to increased permeability and (iii) microbial translocation of cell wall antigens and bacteria, which stimulates (iv) mucosal inflammation leading to (v) systemic inflammation which leads to increased demands for essential nutrients (e.g. amino acids), whose bioavailability may be limited by (vi) maldigestion caused by alterations to brush border architecture and enzyme activity and (vii) malabsorption caused by changes to the expression of nutrient transport proteins in epithelial cells. At the present time, it is not possible to determine how this network of functions is interrelated, and which functions are critical to resolve without new tools to assess each of these domains.\n\nThe urgent problem which we aim to address in the GI Tools study is the dearth of measurement tools to assess the gut functional capacity of communities affected by EE. These tools will 1) be essential for evaluating gut functional capacity in adults (across many disease states) 2) have the potential to assess gut functional capacity in children because of their largely non-invasive nature, and 3) direct the development of new therapeutic interventions to support optimal gut function, for example, recovery of children hospitalised with SAM.\n\n\nAims and objectives\n\nThe overarching objective of the GI Tools project is to develop a novel portfolio of tools for evaluating gut functional capacity in EE and malnutrition disorders. This protocol will allow for the determination of safety, acceptability, dosing, and timing for novel tools to evaluate gut functional capacity in adults with EE. This will be translated to work in malnourished children in further phases of this work.\n\nAim 1: Evaluate a novel portfolio of stable isotope-based tools for evaluating carbohydrate and protein digestion and amino acid absorption.\n\nAim 2: Test a novel non-invasive fluorescence sensor-based tool for real-time evaluation of gut permeability.\n\nAim 3: Characterise the microbiome and metabolome across well characterised and novel physiological sites (duodenal aspirate, duodenal mucus, duodenal tissue, stool, plasma, urine).\n\nAim 4: Quantify systemic and intestinal inflammation using established biomarkers of EE, immune cell phenotyping, epithelial PRR expression, and in vitro epithelial barrier models.\n\nAim 5: Determine if antibiotics, given intravenously, permeate into the gut lumen in sufficient quantities to modulate the microbiota.\n\nAll of these will be correlated with histological mucosal morphometry, lactulose permeation, and established biomarkers of EE.\n\n\n\n• A study of 80 adults with EE will develop novel analytical tools to demonstrate their viability and effectiveness for the assessment of gut functional capacity compared with current ‘gold standards’.\n\n• This study will inform future work on EE disease assessment and in treating children with severe acute malnutrition (SAM) and/or stunting.\n\n• These novel tools will have practical applications in clinical assessments not only in EE but other conditions that affect gut functional capacity allowing better understanding of the underlying mechanisms of different diseases.\n\n• A limitation of this study is the lack of country-specific controls in whom the same assays would be performed for comparison.\n\n• Including adults only in this study limits the applicability of some of the analytical methods when designing a child-based study due to smaller sample volumes.\n\n\nMethods\n\nThe expected outcomes for each aim are shown in Table 1.\n\n\n\nI. Faecal species abundance and diversity indexes by 16s rRNA sequencing.\n\nII. In country deep metagenomic sequencing by long read (Nanopore) sequencing compared with other short-read platforms (Illumina).\n\nIII. Evaluation of microbial communities in EE and their ability to uptake intestinal amino acids, including conversion of L-amino acids to D-forms.\n\n\n\nI. Untargeted metabolomics (1H-NMR) of plasma, urine and faecal water.\n\nII. Targeted quantification (MS) of intestinal, plasma and urine amino acids (unlabelled + labelled) before and after administration of oral and intravenous stable isotopes.\n\n\n\n1) Proteomic analysis of intestinal biopsies for expression of key mucosal proteins in biopsies (including mucins).\n\n2) Dynamic proteomic analysis of key target proteins to assess mucosal protein synthesis rates in biopsies by high resolution MS and D2O labelling.\n\n\nMaterials and analysis\n\nThis cross-sectional study will be conducted in adults in Zambia using a range of stable isotope labelled amino acids and fluorescent tracers,1,19 systemic immune assessments, EE biomarker analysis, microbiome and metabolome analysis, enzyme functional capacity, proteomics and metaproteomic analysis, barrier integrity and function capacity analysis using cell lines, antibiotic reverse permeation, duodenal morphometry, and duodenal expression of PRR to identify potential new tools for measuring gut functional capacity in Zambian adults with EE. In a sub-study in Zimbabwean adults, we will explore the extent to which antibiotics leak from systemic circulation into the gut, where they may modulate the microbiota.20 The study will be carried out in Harare, where sampling of caecal luminal fluid collected at colonoscopy will be used to quantify reverse permeation of intravenously administered benzylpenicillin from the systemic circulation into the gut lumen. Future work will focus on refinement and simplification of these techniques to make them suitable for use in children.\n\nThe initial study will be conducted in 80 adults from a population in Lusaka, Zambia, where our previous studies have demonstrated that EE is virtually ubiquitous in adults and children. A further 20 patients attending for routine colonoscopy (for diagnostic purposes) in Harare, Zimbabwe will be enrolled for the antibiotic permeation study.\n\nAs there are no, or very limited, data on these measurements in this population, the study was powered based on previous studies using stable isotope breath tests and permeability studies. Previous data from an enteropathy vs. healthy child cohort and 13C-sucrose breath tests21 has suggested that calculating the cumulative 13CO2 excretion, % relative to the dose, at 90 minutes post-intake best represents the villus integrity and the absorption capacity of only the small intestine. Preliminary data have shown that in a group of adults from Misisi with demonstrable sucrase-isomaltase (SI) expression in biopsies, the mean cumulative % of dose excreted as 13CO2 at 90 minutes is 20.29% compared to 16.02% in the group without SI expression, with SD of 5.29% – resulting in an effect size (ES) of 0.81. With α=0.05, power =(1-β) = 0.80 we estimate we need 20 samples per group for achieving 80% power with a one-tailed test. We will recruit 30 participants into the definitive studies, allowing for potential dropouts and incomplete sample sets. To estimate sample size for permeability studies we used data on circulating LPS concentrations in stunted children which were mean 481 EU/ml (SD 408) in Lusaka, compared to controls (mean 192, SD 113). This results in an effect size of 0.96, with α=0.05 and power=0.80 and we would require 18 in each group for a two-tailed test. The overall sample size was set at 80 adults to allow for sufficient power to cover a range of studies in adults and children.\n\nConsent will begin with an invitation delivered door-to-door, at which all household members eligible to participate will be invited to group discussions. The study group discussion meetings will include the following:\n\n• Introduction to the study team.\n\n• Introduction to the study rationale and protocol in full; explanation of the study.\n\n• Reading of participant information sheet in Nyanja or Shona; literacy rates in Misisi and Harare are variable, and this is therefore the most appropriate method for conveying this information.\n\n• Benefits and risks of being involved in the research.\n\n• Previous participants’ descriptions of being involved in research which includes endoscopy.\n\n• Questions to previous participants.\n\n• Questions to the study team regarding the study.\n\n• Invitation to attend a guided tour of the research and endoscopy facilities.\n\nPotential participants who are unable to make any of the focus group meetings will be invited to the field clinic to discuss the information sheet and study procedures with a member of the study team. All potential participants will be invited to provide written informed consent in individual interviews with a member of the study team afterwards. They will be invited to ask further questions or express concerns. If happy to proceed, they will be asked to sign or thumbprint the consent form, which will be read out to them in the language of their choice if they are unable to read. Consenting and enrolment will occur at least 48 hours after they have attended a focus group meeting or study explanation visit. Only participants who give consent will undergo screening and enrolment into the study. However, if for any reason during the study, the participant decides to withdraw, they will be allowed to exit the study but will not be replaced.\n\nThis study will include and exclude participants following the criteria shown in Table 2.\n\n\n\n• In Lusaka, only residents of Misisi compound will be included.\n\n\n\n• This study will not include any individuals taking medication for type II diabetes.\n\n\n\n• In Harare, only patients from high socio-economic status (i.e., living in detached houses with indoor flush toilets, tiled floors, separate kitchens with running water and indoor stoves, and own at least one vehicle) will be included.\n\n\n\n• Any contra-indication to study procedures including endoscopy, such as likely to cause problems with sedation (e.g., oropharyngeal anomaly, previous adverse reaction) or biopsy (e.g., bleeding diathesis).\n\n\n\n• Participants of either sex will be included in the study.\n\n\n\n• Pregnant or lactating.\n\n\n\n• Participants aged between 18 and 65 years old.\n\n\n\n• Currently taking any anticoagulants.\n\n\n\n• Only participants who are able and willing to undergo HIV testing.\n\n\n\n• Having renal failure or liver failure (any major organ system).\n\n\n\n• Able and willing to give written, informed consent will be included.\n\n\n\n• Any underlying condition, other than HIV, which in the opinion of the investigator would put the subject at undue risk of failing study completion or would interfere with analysis of study results.\n\n\n\n• Participants will be temporarily excluded from study procedures if they have had diarrhoea (by self-report) in the preceding month, and have taken antibiotics, non-steroidal anti-inflammatory drugs, and/or proton pump inhibitors in the preceding month until disqualifying condition has elapsed.\n\n\nProtocol\n\nParticipants will be consented for HIV testing as part of the consent process, before enrolment. Consenting for HIV testing and communication of results will be performed by an experienced and fully trained team of research staff and counsellors. HIV counselling and testing have been performed by this team both as part of standard medical care in the Misisi clinic and as part of the routine research process in our recent studies for over 15 years.10,22 Likewise, HIV counselling and testing are standard of care in Zimbabwean health care facilities. HIV test results will be given in person and confidence in the clinic of recruitment. Participants found to be HIV seropositive will be allowed to discuss their results and management in more detail. With their consent, they will be referred to HIV specialists for further investigation and management including anti-retroviral therapy per Ministry of Health guidelines and procedures in both Zambia and Zimbabwe. Test results remain confidential and will not be shared with anyone outside of the study team without the participant’s explicit consent.\n\nAll anthropometry measures will be taken by qualified research nurses trained in anthropometry. Weight will be measured using a calibrated scale, standing height using a height scale, and mid-upper arm circumference (MUAC) using a MUAC tape. Grip strength will be measured using a Takei Grip-D dynamometer, waist and hip circumferences using a measuring tape, and lean and fat mass using a BodyStat® 1500 Impedance instrument (BodyStat®, Douglas, Isle of Man).\n\nA multi-pass 24-hour dietary recall will be used to assess participants on day 2. All participants will be asked about the food they may have had in the last 24 hours which will be documented (Described in detail elsewhere.23 While this 24-hour period may not be representative of the participants’ habitual intake, it was intended primarily to help interpretation of the metabolic profiling and thus would be most useful prior to the collection of samples for metabolic analysis.\n\n\nClinical investigations: Zambia\n\nInvestigations will be carried out over a four-day period (shown in Figure 2).\n\nSchema showing each sample collection time point throughout study, Day 1; No samples will be collected; Day 2; 9 mL heparinised blood; 2 mL EDTA blood; 5 mL citrated blood; 11 mL Urine at 00 and 180 mins; 4-8 g of stool; 0.5-2 mL of saliva at 00 and 180 mins; and breath samples every 20 mins. Day 3: 9 mL of heparinised blood; intermediate 2 mL heparinised blood samples every 20 mins for 1 h and every 30 mins for the last 2 h; breath samples every 20 mins; 0.5-2mL of saliva at 00, 60, 120 and 180 mins; 7 mL of urine at 00 and 180 mins; 4-8 g stool; 8 duodenal biopsies and 1 duodenal brushing; Day 4; 2-4 g of stool and 11 mL of urine.\n\nThis will include the final consent interview, administration of a questionnaire by the study nurse, clinical examination, and anthropometry (including weight, height, impedance, and deuterium approaches to body composition). Urine and stool collection devices will also be given.\n\nParticipants will bring urine and stool samples with them. Before administration of the solutions, a saliva sample, 9 mL of blood will be collected in lithium heparin, 2 mL in EDTA and 4.5 mL in citrated blood collection tubes, respectively, by venepuncture. A drink (prepared as shown in Table 3) of 2H2O (deuterated water, 1 g 2H2O per kg body weight) containing 13C-spirulina protein (1.25 mg kg−1) and (2H8)-Phe (0.035 mg kg−1 in 200 mL clean water) will then be given at, or close to, 08:00 followed by breath sample collection using a straw and Exetainer tube (Labco, UK) every 20 mins for the first 1 h and every 30 mins for the remaining 3 h. A saliva sample will be collected at 180 mins, and a urine sample collection at 180 mins (3 h). A second drink of 2H2O (1 g 2H2O per kg body weight) will be given at 180 mins (3 h). During these procedures, a multi-pass 24-hour dietary recall will be administered by the study nurse. At the end of the procedures, the participant will be asked to fast after midnight and given stool and urine collection devices in readiness for day 3 procedures.\n\n\n\n• Deuterated water (D2O) (1 mL per kg body weight),\n\n• 13C-spirulina protein (1.25 mg kg−1), and\n\n• (2H8)-Phe (200 mg) in 200 mL water\n\n\n\n• Deuterated water (D2O) (1 mL per kg body weight)\n\n\n\n• 2H5-Phe (0.6 μmol kg−1),\n\n• 5,5,5-2H3-Leu (1.2 μmol kg−1)\n\n\n\n• 2H5-Phe (0.15 μmol kg−1)\n\n• 5,5,5-2H3-leucine (0.3 μmol kg−1)\n\n\n\n• 13C6-Phe (0.6 μmol kg−1),\n\n• 13C6-Leu (1.2 μmol kg−1),\n\n• 5 g lactulose,\n\n• 1 g rhamnose,\n\n• 0.5 g D-xylose,\n\n• 0.2 g 3-O-methyl D-glucose,\n\n• 200 mg sodium fluorescein,\n\n• 1.667 mg L-arginine-(guanidineimino-15N2) HCl,\n\n• 1.0 g glycyl sarcosine\n\n\n\n• 13C6-Phe (0.15 μmol kg−1)\n\n• 13C6-Leu (0.3 μmol kg−1)\n\nFollowing an overnight fast, an intravenous cannula will be introduced into both arms and 5 mL of blood will be collected into a lithium heparin tube via cannula. The fingertip probe will be clamped gently onto a fingertip, and continuous fluorescence recordings will begin. An intravenous bolus of 2H5-phenylalanine (0.6 mmol kg−1) and 5,5,5-2H3-leucine (1.2 mmol kg−1) in 10 mL normal saline filtered through a 0.2 mm syringe filter (solution C) will be given over 2 mins, and an oral bolus of 13C6-leucine (1.2 mmol kg−1), 13C6-phenylalanine (0.6 mmol kg−1), 5 g lactulose, 1 g rhamnose, 0.5 g D-xylose, 0.2 g 3-O methyl-D-glucose, 200 mg fluorescein, 1.667 mg L-arginine-(guanidineimino-15N2) HCl and 1.0 g glycyl sarcosine (solution E) given. A continuous intravenous infusion of 2H5-phenylalanine (0.15 mmol kg−1) and 2H3-leucine (0.3 mmol kg−1) (solution D) will be commenced, at 5 mL h−1, and sips of 13C6-phenylalanine (0.15 mmol kg−1) and 13C6-leucine (0.3 mmol kg−1) (solution F) administered as sips every 20 mins (prepared as shown in Table 3). Breath samples will be collected every 20 mins for the first 1 h and every 30 mins for the remaining 3 h. Blood samples will be collected into lithium heparin collection tubes via the intravenous cannula: 2 mL every 20 mins for the first 1 h and every 30 mins for the remaining 3 h, and 5mL for the last sample. Urine will be collected up to 180 mins (3 h) while saliva collected every 60 mins for 3 h. After 240 mins (4 h) the participant will be transferred to the endoscopy room where upper gastrointestinal endoscopy will be performed using doses of sedation with midazolam and pethidine selected by the endoscopist. Oximetry will be used throughout the procedure. During endoscopy, up to 10 mL of duodenal aspirate will be collected with clean tubing. Using the same tubing, 20 mL 0.9% of sterile saline will be used to collect duodenal lavage. A brushing will be collected using an endoscopic cytology brush, and then the brush will be cut off into 1000 μL PBS. For histology, 3 biopsies will be collected into normal saline using 2.8 mm biopsy forceps, orientated on cellulose acetate paper (Sartorius, Gottingen, Germany) in the endoscopy room and placed in formalin thereafter. An additional 5 biopsies will be collected into 3 cryovials (2+2+1). All samples collected during endoscopy, except for the 3 histology biopsies, will be snap-frozen in liquid nitrogen immediately after collection. At the end of day 3, the participant will be given urine and stool collection devices for the next day.\n\nOnly stool and urine samples will be collected.\n\n\nColonoscopy: zimbabwe\n\nAn intravenous injection of a single dose of 600 mg benzylpenicillin will be given in patients presenting for colonoscopy, 10 – 15 minutes before the procedure. Luminal fluid from the right side of the colon will be aspirated between 20 and 40 mins after benzylpenicillin administration. This fluid will be centrifuged, stored, and shipped to Imperial College where the assays for the presence of benzylpenicillin, which will indicate reverse permeation, will be performed.\n\n\nSample handling\n\nSamples for safety analysis (differential blood count using the Sysmex XP300™ automated haematology analyser (Sysmex UK Ltd., Milton Keynes, UK) and prothrombin time using the HumaClot Junior (HUMAN Diagnostics Worldwide, Wiesbaden, Germany)) will be processed immediately; excess samples will be retained as backup, but destroyed once the study is complete. Samples for research assays (Table 4) will be analysed immediately or stored at appropriate temperatures (usually -80°C). Blood samples from Day 2 (9 mL) will be centrifuged (2,300 g for 5 minutes at 4°C) to separate plasma from buffy coat cells (enriched for immune cells) and red blood cells; plasma will be aliquoted and stored at -80°C and buffy coat cells will be treated to lyse red blood cells, fixed, washed, re-suspended in cell preservation media, and cryopreserved gradually to -80°C using cell freezing containers to maintain cell integrity. On day 3, blood collected at different time intervals in lithium heparin (Table 4) will be centrifuged under the same conditions to separate plasma which will be aliquoted and stored at -80°C. Stool samples collected on days 2, 3 and 4 will be aliquoted and stored at -80°C. All saliva samples collected on days 2 and 3, all urine and stool samples collected on days 2, 3, and 4 will also be aliquoted and stored at -80°C. All breath samples that will be collected on days 2 and 3 will be stored at room temperature until analysis. All cryo-stored samples will be retained until batch analyses at either TROPGAN or may be shipped to the relevant external laboratories for analyses (shown in Table 4). For sample types being shipped for analyses at external laboratories, an aliquot of each will be retained at TROPGAN wherever possible; these aliquots will act as a backup in case of analytical failures, or storage failures during transport to another laboratory.\n\n\nClinical assessments\n\nThe permeability will be measured by the appearance in the blood of fluorescein ingested orally. Fluorescein has a similar molecular size to lactulose. We have previously demonstrated that the rate and degree of permeation of fluorescein vary under different permeability conditions24 and in patients with intestinal disorders.25 Importantly, following permeation into the blood, fluorescein fluorescence is quantifiable using a fingertip probe similar to a pulse oximeter probe.26\n\n\nLaboratory assessments\n\nThe non-radioactive stable isotope labelled amino acids are used to trace the digestion and absorption of protein (day 2) and bidirectional transmucosal amino acid flux (day 3). The labelling strategy is chosen to minimise isotopic crosstalk in the analysis and maximise the metabolic pools that can be sampled ethically. These include breath (13CO2), plasma (13C / 2H amino acids), intestinal aspirates (13C / 2H amino acids), and urine (13C / 2H amino acids). Breath samples will be analysed using a Thermo Scientific™ Delta Ray™ Isotope Ratio Infrared Spectrometer (Thermo Fisher Scientific, Bremen, Germany) in the TROPGAN laboratory (breath 13CO2) and 13C & 2H labelled amino acids analysed by a Agilent 1290 Infinity LC coupled to a 6560 triple quadrupole mass spectrometer (Agilent Technologies Inc., Cheadle, UK) in SUERC (13C/2H amino acid isotopologues).\n\nUrine, stool, plasma, and duodenal aspirates will be analysed by Nuclear Magnetic Resonance spectroscopy (NMR). High-throughput 1H NMR spectra will be acquired using a 600MHz Bruker Avance III™ HD NMR spectrometer equipped with a 5 mm BBI Z-gradient probe, high-order shims, and automated tuning and matching (Bruker Biospin, Rheinstetten, Germany). Samples will be analysed in automation using standard pulse sequences with water suppression. For urine, stool, and duodenal aspirates, two experiments will be acquired: (1D) 1H NMR (noesygppr1d, standard Bruker pulse program), and (2D) 1H−1H J-resolved (J-Res) experiment (jresgpprqf). (1D) 1H CPMG (Carr–Purcell–Meiboom–Gill, cpmgpr1d) will also be acquired for plasma only. Each 1D spectrum will be automatically phased and baseline corrected, digitized, and imported into MATLAB for preprocessing and statistical modelling.\n\nStool samples, gastric and duodenal aspirates and intestinal biopsies will undergo nucleic acid extraction, library construction and whole metagenome shotgun sequencing at Imperial College London to identify taxonomic and functional composition of multi-site gastrointestinal microbiomes comparing standard short-read sequencing approaches (Illumina HiSeq™ (Illumina, San Diego, CA, USA)) with novel long-read approaches (MinION (Oxford Nanopore Technologies Ltd., Oxford, UK) and PacBio Sequel® (Pacific Biosciences Inc., Menlo Park, CA, USA)). These sequencing efforts will be duplicated in parallel work in Lusaka to determine the ease of application to an African laboratory. Additional characterisation of microbial uptake of amino acids and conversion of L to D amino acids will also be carried out. Raw sequencing data will be analysed via established bioinformatics pipelines including DADA2 (for 16S rRNA genes), EPI2ME and MetaPhlAn3 (compositional), HUMAnN3 (functional) as with other data, these results will be compared with duodenal biopsy histology, lactulose permeation data, and biomarkers.\n\nFormalin fixed biopsies will then be embedded in wax. Sections (4 μm) will be stained using haematoxylin and eosin (H&E) and scanned on an Olympus VS120® scanning microscope (Olympus Corporation, Tokyo, Japan). Morphometry will be performed to generate measurements of villus height and crypt depth as has been our standard practice for many years and on which several publications are based.8,27,28 Recently a histological scoring system for EE has been developed in which we were involved, and this will be applied to generate scores for villus architectural change, Brunner’s gland penetration, Paneth cell depletion, Goblet cell depletion, intra-epithelial lymphocytosis, and epithelial abnormalities.29 The expression of PRRs will be assessed in separate histological sections of antibody-labelled duodenal biopsies via immunofluorescence microscopy.\n\nTo characterise the sample sets fully, giving context to observed changes in the composition of the microbiota, biomarkers of EE (shown in Table 5) will be quantified in plasma and stool aliquots via ELISA.\n\nTo evaluate the capacity of circulating microbial products in plasma and microbial content in stool to activate innate immune signalling (immunogenicity), plasma and faecal water aliquots from each participant will be co-cultured with reporter cell lines (e.g. HEK293, THP-1) for innate immune cell signalling activity. We will add aliquots of plasma/fecal water to the basal/apical side of in vitro transwell models of the gut epithelial barrier to evaluate their effect on barrier integrity, permeability, PRR expression, and cellular activation.\n\nIn the 20 patients attending for routine colonoscopy (for diagnostic purposes) in Harare, using luminal fluid, antibiotic analysis will be carried out by NMR or SUERC by LC-MS.\n\nWith the complexity of the data set from the techniques described above, the biostatistical framework will be generated in a data-dependent manner. Data from novel tools will be integrated with mucosal morphometry, lactulose permeation, and biomarkers in blood and stool. All data will be tested for normality using a Shapiro-Wilk test and transformed accordingly (normalisation, scaling, etc.). Both parametric and non-parametric tests will be used and both univariate and multivariate analysis will be performed on all datasets generated, as appropriate. For univariate tests, to control for type-I errors, multiple testing will be corrected for by applying the Hommel correction (for Family-Wise Error Rate) or Benjamini-Hochberg (for False Discovery Rate) as appropriate for mildly (positively) correlated variables, or Benjamini-Yekutieli or Storey-Tibshirani (both for False Discovery Rate) methods for highly (positively and inversely) correlated variables. For multivariate tests, data will first be split into training (modelling) and test (evaluation) sets prior to any procedures on the data such as centering, scaling, or other transformations. The predictive classification models will be calculated only on the training portions and evaluated (accuracy and/or F1-score) on the test portions, with hyperparameter tuning using cross-validation on the training data. When small sample sizes do not allow setting aside a completely independent test set, repeated cross-validation will be used to ensure the robustness of the models by calculating a multitude of models (e.g. 1,000 individual models). The evaluation of performance is estimated across all models on the portion of the data that was set aside (test) in each partition. Where algorithms use random initializations of parameters, for each analysis the starting random number seed is saved to allow replication. All data generated will be compared with all duodenal morphometry data which is the most direct measure of EE severity; these comparisons will allow for validation of new real-team assessment tools and established laboratory techniques for sensitivity to differences in EE severity within the cohort.\n\nDissemination will include the participants and their families, together with Community Advisory Boards, the University of Zambia School of Medicine, and the University of Zimbabwe Faculty of Medicine and Health Sciences. We will also disseminate results to the Zambian National Health Research Authority and the Medical Research Council of Zimbabwe, and the relevant ethics committees in all the African partner countries, both in written form and by taking opportunities of local research dissemination meetings. This is established practice in all the research groups who will be collaborating on the work proposed. All publications will be open access.\n\nData will be stored on desktop computers until data cleaning is complete, after which locked databases will be uploaded onto secure, password-protected cloud-based systems. Only authorised personnel will have access to the data. All databases will be archived with related questionnaires and any related dictionaries in soft copy on the same drive(s). Long term storage will be on secure cloud-based systems hosted at the Sponsor, QMUL. All data records and materials will be archived appropriately (in accordance with ICH GCP Guidelines) and retained for 5 years according to the Sponsor’s requirements. Data with identifiers will not be stored, for example, personal identifiers on the front sheet of all clinical trial records will be detached prior to archiving and will not be entered on any database. These identifiers will be kept as hard-copy files in locked cabinets in study offices.\n\nData security and confidentiality will be in line with General Data Protection Regulations, HRA Guidance, International Conference on Harmonisation, Guideline for Good Clinical Practice E6, Revision 2, and Queen Mary University of London Data Protection principles and policies. Only authorised study personnel will have access to study files and data. Any data that will be shared with other workers in the field will be anonymised. Identifiable personal data will not be used during analysis or when publishing results. The information that is collected will be treated confidentially. The information entered on separate forms only contains a participant number and the initials and only the data considered important for the study. Research staff are aware of confidentiality of personal data and meeting the requirements of the General Data Protection Regulation (GDPR). Personal information will only be used to contact the patient via letter or telephone after informed consent has been obtained. The only link between personalised data and anonymised data will be a register kept in hard copy in a locked cupboard by the compliance manager. Data will be maintained at an appropriate vigilance (RAID 1) level following current institutional advice. Data access will be restricted to only authorised personnel with individual passwords.\n\nThe protocol has been approved by the National Heath Research Agency (REF NHREB00001/02/2022, dated 2nd February 2022) and the University of Zambia Biomedical Research Ethics Committee (reference number 2291-2021, dated 20th December 2021). The Zimbabwean studies have been approved by the Medical Research Council of Zimbabwe (MRCZ/A/3065, dated 31 July 2023). The work will be carried out in full concordance with the principles of the Declaration of Helsinki, and all participants will give written consent. Queen Mary Ethics of Research Committee issued a letter of no objection (QMERC22.060, dated 22nd February 2020).\n\n\nDiscussion\n\nOur project will take a holistic approach to understanding the impact of EE on gut functional capacity across the whole gastrointestinal tract, which means developing new tools for assessing multiple domains of physiology. This necessitates an assessment of the structure of the intestine (e.g., reduced villus height and therefore surface area, barrier function), digestive and absorptive capacity (e.g., enzyme activity for protein, fat and carbohydrate digestion, transporter expression for absorption), epithelial and immune responses to pathogens, PAMPs, and the microbiota, and the health of the gut microbiota and its metabolic activity. Through this study, we will be able to identify and select the combination of functional measures that are most sensitive to variations in gut physiology according to EE severity in this adult cohort. We will also be able to optimise protocols for communities, such as Misisi, where EE is the predominant gut phenotype. Such measurements will ultimately enable the design of novel therapeutic feeds which actively promote improved gut functional capacity, providing a novel approach to accelerate sustained rehabilitation, reduce mortality, and feed the superorganism (i.e., the host and microbiome), thereby improving growth in malnourished children.14,17 The urgent problem which we aim to address in this proposal is the dearth of investigative tools available to measure these pathophysiological domains. These tools will be essential for the effective evaluation of new therapeutic feeds to be trialled in SAM and, critically, the selection of those that promote the healing of underlying defects as well as weight gain. Their application to childhood malnutrition will be highly original especially when linked to a clinical trial addressing patient-centred outcomes. Our research group will go on to conduct longitudinal studies and/or clinical trials to evaluate further the tools we will develop. This will provide a deeper understanding of the changing physiology and will generate essential data to support the findings of the trial. In the scenario where no benefit of a novel therapeutic intervention or feed is shown, our novel tools may provide essential for future refinements of the feeds to target specific domains of gut functional capacity and/or enhance effects on pathways showing positive sub-clinical modifications.\n\nIn more general terms, these tools may find applications in patients with other enteropathies such as coeliac disease, or enteropathies consequent on cancer therapy. Objective measures of intestinal dysfunction may also help manage patients with intestinal failure. We believe that the strategy of using stable isotopes, fluorescence probes, and new sequencing tools to measure intestinal digestion and absorption, barrier function, and the function of the microbiome, will remain of great interest for years to come.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nMendeley Data: GI Tools SPIRIT Checklist, http://doi.org/10.17632/2536bhwx7g.1. 30\n\nThe project contains the following underlying data:\n\n- GITools_SPIRIT_Fillable-checklist-July2024.pdf\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 remaining data in this article consists of bibliographic references, which are included in the References section.\n\n\nReferences\n\nThompson AJ, Bourke CD, Robertson RC, et al.: Understanding the role of the gut in undernutrition: what can technology tell us? Gut. 2021 Jun 8; 70(8): 1580–1594. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMurray-Kolb LE, Rasmussen ZA, Scharf RJ, et al.: The MAL-ED cohort study: methods and lessons learned when assessing early child development and caregiving mediators in infants and young children in 8 low- and middle-income countries. Clin. Infect. Dis. 2014 Nov 1; 14(Suppl 4): S261–S272. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNabukeera-Barungi N, Grenov B, Lanyero B, et al.: Predictors of mortality among hospitalized children with severe acute malnutrition: a prospective study from Uganda. Pediatr. Res. 2018 Jul; 84(1): 92–98. PubMed Abstract | Publisher Full Text\n\nTalbert A, Thuo N, Karisa J, et al.: Diarrhoea complicating severe acute malnutrition in Kenyan children: a prospective descriptive study of risk factors and outcome. PLoS One. 2012; 7(6): e38321. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBwakura-Dangarembizi M, Dumbura C, Amadi B, et al.: Recovery of children following hospitalisation for complicated severe acute malnutrition. Matern. Child Nutr. 2022 Apr; 18(2): e13302. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKerac M, Bunn J, Chagaluka G, et al.: Follow-up of post-discharge growth and mortality after treatment for severe acute malnutrition (FuSAM study): a prospective cohort study. PLoS One. 2014 Jun 3; 9(6): e96030. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSow SO, Muhsen K, Nasrin D, et al.: The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS). PLoS Negl. Trop. Dis. 2016 May 24; 10(5): e0004729. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmadi B, Zyambo K, Chandwe K, et al.: Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting. Nat. Microbiol. 2021 Apr; 6(4): 445–454. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKummerlowe C, Mwakamui S, Hughes TK, et al.: Single-cell profiling of environmental enteropathy reveals signatures of epithelial remodeling and immune activation. Sci. Transl. Med. 2022 Aug 31; 14(660): eabi8633. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmadi B, Besa E, Zyambo K, et al.: Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy in Zambia. EBioMedicine. 2017 Aug; 22: 191–199. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJones KD, Berkley JA: Severe acute malnutrition and infection. Paediatr Int Child Health. 2014 Dec; 34(Suppl 1): S1–S29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSturgeon JP, Mufukari W, Tome J, et al.: Risk factors for inpatient mortality among children with severe acute malnutrition in Zimbabwe and Zambia. Eur. J. Clin. Nutr. 2023 Sep; 77(9): 895–904. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSturgeon JP, Tome J, Dumbura C, et al.: Inflammation and epithelial repair predict mortality, hospital readmission, and growth recovery in complicated severe acute malnutrition. Sci. Transl. Med. 2024 Feb 28; 16(736): eadh0673. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSubramanian S, Huq S, Yatsunenko T, et al.: Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature. 2014 Jun 19; 510(7505): 417–421. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOwino V, Ahmed T, Freemark M, et al.: Environmental Enteric Dysfunction and Growth Failure/Stunting in Global Child Health. Pediatrics. 2016 Dec; 138(6): e20160641. PubMed Abstract | Publisher Full Text\n\nGehrig JL, Venkatesh S, Chang HW, et al.: Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science. 2019 Jul 12; 365(6449): eaau4732. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen RY, Mostafa I, Hibberd MC, et al.: A Microbiota-Directed Food Intervention for Undernourished Children. N. Engl. J. Med. 2021 Apr 22; 384(16): 1517–1528. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBarratt MJ, Nuzhat S, Ahsan K, et al.: Bifidobacterium infantis treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition. Sci. Transl. Med. 2022 Apr 13; 14(640): eabk1107. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDorshow RB, Johnson JR, Debreczeny MP, et al.: Transdermal fluorescence detection of a dual fluorophore system for noninvasive point-of-care gastrointestinal permeability measurement. Biomed. Opt. Express. 2019 Sep 13; 10(10): 5103–5116. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKelly P, Besa E, Zyambo K, et al.: Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy. PLoS Negl. Trop. Dis. 2016 Apr 6; 10(4): e0004600. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRitchie BK, Brewster DR, Davidson GP, et al.: 13C-sucrose breath test: novel use of a noninvasive biomarker of environmental gut health. Pediatrics. 2009 Aug; 124(2): 620–626. PubMed Abstract | Publisher Full Text\n\nLouis-Auguste J, Kelly P: Tropical Enteropathies. Curr. Gastroenterol. Rep. 2017 Jul; 19(7): 29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJobarteh ML, McCrory MA, Lo B, et al.: Development and Validation of an Objective, Passive Dietary Assessment Method for Estimating Food and Nutrient Intake in Households in Low- and Middle-Income Countries: A Study Protocol. Curr Dev Nutr. 2020 Feb 7; 4(2): nzaa020. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGan J, Monfort SE, Avery J, et al.: Non-invasive assessment of intestinal permeability in healthy volunteers using transcutaneous fluorescence spectroscopy. Methods Appl Fluoresc. 2022 Oct 10; 10(4): 044014. PubMed Abstract | Publisher Full Text\n\nMbuki R, Chileya S, Thompson AJ, et al.: Rapid testing of gut permeability using oral fluorescein and confocal laser endomicroscopy in Zambian adults. Trans. R. Soc. Trop. Med. Hyg. 2021 Oct 1; 115(10): 1226–1228. PubMed Abstract | Publisher Full Text\n\nSanchez EM, Avery J, Gan J, et al.: Transcutaneous fluorescence spectroscopy: development and characterization of a compact, portable, and fiber-optic sensor. J. Biomed. Opt. 2024 Feb; 29(2): 027003. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMulenga C, Sviben S, Chandwe K, et al.: Epithelial Abnormalities in the Small Intestine of Zambian Children With Stunting. Front Med (Lausanne). 2022 Mar 16; 9: 849677. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLouis-Auguste J, Greenwald S, Simuyandi M, et al.: High dose multiple micronutrient supplementation improves villous morphology in environmental enteropathy without HIV enteropathy: results from a double-blind randomised placebo-controlled trial in Zambian adults. BMC Gastroenterol. 2014 Jan 15; 14: 15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu TC, VanBuskirk K, Ali SA, et al.: A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth. PLoS Negl. Trop. Dis. 2020 Jan 13; 14(1): e0007975. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWeatherill J: GI Tools SPIRIT Checklist. Mendeley Data. V1. Publisher Full Text"
}
|
[
{
"id": "326299",
"date": "17 Oct 2024",
"name": "Pascale Vonaesch",
"expertise": [
"Reviewer Expertise childhood undernutrition",
"environmental enteropathy",
"human microbiome",
"small intestinal microbiome",
"biomarker analysis",
"clinical microbiome research in Sub-Saharan Africa and South-East Asia"
],
"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 describe a study to take place in Zambia and Zimbabwe, aiming at assessing for possible biomarkers of environmental enteric disorder (EED). They propose to study this in a group of adults which undergo collection of different biospecimens, including blood and stool samples as well as endoscopy and duodenal sampling, allowing to correlate the potential biomarkers with the gold standard, based on histology of the small intestinal mucosa.\nThe study is interesting, well designed and addresses a pressing problem, as to date, there are still no widely accepted, easy to measure biomarkers for EED that clearly delineate the disease and distinguish it from other syndromes/infections affecting the GI tract. The study is very interesting as it assesses for macronutrient digestion and absorption as well as intestinal permeability using advanced techniques in homo. These analyses are combined with a description of the duodenal microbiota using 16S and shotgun metagenomic sequencing, performed in parallel in Africa as well as in the UK using Nanopore technology.\nThe study protocol reads very nicely and is complete in its approach and description.\nMajor points: My main concern for the study is the introduction and reference list, which is currently biased towards work from the consortium, leaving out previous work performed on biomarkers in studies performed on children by consortia located in Bangladesh, Pakistan, the Central African Republic and Madagascar. In my opinion, even if the target group is children, adding this previous work would greatly strengthen the point of the study performed and situate it better in the overall research performed so far. It would furthermore also give credit to previous work from other groups on the same/similar subject.\nFurthermore, the description on previous work on the (duodenal) microbiota in undernutrition and EED is very scarce and misses to cite previous work in children in the Bangladeshi cohort (Chen R, et al., 2020 [Ref 1]), the Pakistan cohort (Iqbal et al., mSphere 2024 [Ref 3]) and the Afribiota project (Vonaesch et al., PNAS 2018 & 2022 [Ref 2]). Indeed, these studies were the first to show decompartmentalization of the GI tract (first mentioned in Vonaesch et al., PNAS 2018) in stunted growth and EED and could show first hints that the duodenal microbiota could be causally linked to the EED pathophysiology (Chen R, et al., 2020 [Ref 1], Vonaesch et al., 2022 [Ref 2]). This link is currently missing in the manuscript. Furthermore, the authors also do not mention previous work linking EED with decreased lipid absorption (Vonaesch et al., PNAS 2022) and metabolization (Habermann et al., Gastroenterology 2021 [Ref 4]).\nLast, there is also only limited references provided for the characterization of the immune system associated with undernutrition and EED (see. i.e. Andrianamantena et al., 2022 [Ref 5] among others). While I acknowledge this previous work is performed in children and not in adults like in he proposed study, I think that the information should still be given, even the more as this work was likely motivating the analyses proposed in the current study protocol and as the authors stress the fact that the biomarkers might be used in children thereafter. In conclusion, I strongly encourage the authors to have a more balanced overview of the current state of work on biomarker discovery, the microbiome and EED beyond work performed by the study team in Zambia and in adults.\nSpecific points: In the section on study size estimation, it was not clear to me what the prevalence of sucrase-isomaltase expression is. This information would ease the reader to better understand the overall sample size estimations.\nRegarding the inclusion criteria, it was not clear to me why only patients of high economic status are recruited. Will this not lead to a potential bias? Please explain a bit more in detail, so the rationale behind this choice is more evident to the reader.\nRegarding the consenting and consent withdrawal in the study, it was not clear to me what happens to the data and samples if a patient retracks. Are the data kept and anonymized? Destroyed? This should be clarified.\nRegarding the microbiota analysis, it is not clear to me how the characterization of microbial uptake of AA and the subsequent L to D conversion will be measured. Can this be specified?\nIn addition, seen the importance attributed to the absolute abundance of the microbiome in the small intestinal tract (demonstrated i.e. in Chen et al, 2020), I encourage the study team to also assess for bacterial absolute abundance in Aim3 of their proposed study aims.\nIn the discussion section, it would have been nice to see a bit better how this research is situated in previous work, what it will bring in addition to what has been done before and what the main novelties of this project are compared to previous studies performed on children and/or adults in other countries around the globe. This would allow the reader to better understand the uniqueness and novelty of this study (which is evident to me, but it would be nice to also more clearly showcase this to readers less familiar with the topic).\nMinor points: Page 10, under the heading Day 4: Should this not read: “Colonoscopy: Zimbabwe” (with a capital Z)?\nData management: who has access to the study data? Will the Zambian study team have access to all data also if generated in the UK? How will the data been made openly accessible after publication (future data availability statement)? Please specify this in the study protocol.\nEthical considerations: is there a Nagoya approval needed to export samples from Zambia to the UK? If yes, has this approval been applied for/ been granted? Please provide some information on if and how the Nagoya approval applies to this 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? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
},
{
"id": "317023",
"date": "14 Nov 2024",
"name": "Declan McCole",
"expertise": [
"Reviewer Expertise Intestinal permeability",
"epithelial tight junctions",
"epithelial transport",
"intestinal inflammation."
],
"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 GI TOOLS project is a cross-sectional study that will recruit adults aged 18-65 years with environmental enteropathy (EE) in Lusaka, Zambia that aims to develop new tools for the measurement of gut functional that can be utilized in future clinical trials. The methodology of this project requires each participant to undergo an assessment of gut functional capacity using novel nearpoint-of-care tools and to provide multiple samples for detailed laboratory analyses. Novel techniques include stable isotope approaches to measuring digestion, absorption, and bidirectional transmucosal amino acid flux, a non-invasive fluorescence tool for real-time evaluation of gut permeability, and assessment of gut luminal access of intravenous antibiotics. Stool and duodenal microbiome sequencing, metabolome analysis of plasma and intestinal fluids, blood immune cell phenotyping, in vitro epithelial barrier models, and duodenal immunohistochemistry will also be used to explore EE in depth. These will be integrated with histology and mucosal morphometry using an established histological scoring system for EE, alongside stool and plasma biomarker analysis. The proposal builds on prior foundational work from this consortium that has tested several of the experimental approaches listed in the current proposal. An important feature of the proposal is that local dissemination of research data in Zambia and Zimbabwe will also be undertaken in written form and in presentations at local meetings. This will be an important means of engaging with local research and public health communities. Overall, this represents a very comprehensive set of approaches to functionally characterize the impact of EE on multiple aspects of gut physiology from permeability to digestion of nutrients. The study has high clinical relevance and if it meets its goals it could not only create a new paradigm for functional verification of EE, but also provide robust readouts that could be tested for efficacy of different dietary and therapeutic interventions to rescue subjects from the damaging effects of EE.\nThere are some concerns with the inclusion/exclusion criteria. The preference for inclusion of subjects only from higher socioeconomic backgrounds in the Harare (Zimbabwe) study on i.v. antibiotic pharmaco-distribution requires some explanation and justification.\nWhat considerations will be made if there is a high rate of avoidance of HIV testing?\nWhat size (kDa and diameter) of fluorescein will be used as the permeability probe? This should be specifically stated and the source/catalog number of the actual fluorescein to be used should also be provided.\nSince proteomic analysis of intestinal biopsies will be performed, it should be clarified if tight junction protein expression will be examined as altered expression could correlate with functional changes in permeability – with the caveat that this approach will not identify changes in localization of TJ proteins that occur without any change in expression levels.\nIn Aim 5, Benzylpenicillin is the iv antibiotic that will be used in this study to identify if i.v. administered antibiotics can access the gut lumen. It is unclear what the goal of this aspect of the study is meant to determine. Do the authors consider antibiotic administration to exacerbate symptoms of EE? With respect to the question of whether i.v. antibiotics can enter the gut lumen, this has already been demonstrated that antibiotics can pass into the gut lumen via biliary secretions, and alter bacterial populations (Xue et al, 2023. [Ref 1]). In addition, no explanation of why this particular antibiotic is being used has been included. It is hard to justify this particular aim (#5) as it will not generate any novel findings and could be considered an unnecessary human subjects intervention.\n\nA limitation of the study is that samples will not be collected longitudinally to identify if readings are sustained or transient. However, longitudinal assessment is proposed in the Discussion section describing future studies.\nClarification of the “reporter” characteristics of HEK293, THP-1 cell lines should be provided. Will the group be using modified cells lines expressing actual reporter constructs (i.e. to quantify enzymatic activity) or are these cells just being used as ‘model’ cell lines. Given that changes in gut epithelial physiology are integral to the symptoms of EE, what is the rationale for choosing a kidney epithelial cell line (HEK293) as a model epithelium?\nIn vitro experiments assessing the effect of PAMPs in fecal samples on permeability of intestinal epithelial cell cultures, will likely exhibit responses to bacterial LPS and it is unclear how the authors will be able to screen for effects of other PAMPs (in feces) in this system with any degree of specificity.\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? No\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-956
|
https://f1000research.com/articles/13-955/v1
|
23 Aug 24
|
{
"type": "Research Article",
"title": "Confirmatory Factor Analysis and Propensity to Cheat Scale Validation in the Ethiopian Public Higher Education Institutions",
"authors": [
"Dame Taye",
"Tesfaye Semela",
"Samuel Assefa",
"Tesfaye Semela",
"Samuel Assefa"
],
"abstract": "Background This study was primarily intended to develop and validate a comprehensive and psychometrically acceptable measure of students’ propensity to cheat (PTC) behavior among undergraduate students in Ethiopian universities by assessing their engagement in different types of cheating behavior.\n\nMethods The present study employed an explanatory research design using a questionnaire based on the Propensity to Cheat Scale (PCS). The questionnaire was administered to 500 university students (male = 367 [73.4%]; female = 133 [26.6%]) selected from three Ethiopian public universities between November and January 2022. In order to measure the underlying variables of propensity towards cheating, a factor model is developed using exploratory factor analysis, and confirmatory factor analysis was employed to validate the students’ perceived PTC. The internal consistency of the PTC scale was assessed using reliability analysis, and validity evaluations were conducted to confirm the scale’s discriminant and convergent validity.\n\nResults Confirmatory factor analysis (CFA) results revealed a good fit to the data, and the internal consistency of the PCS was found to be strong, providing a reliable measure of students’ propensity for cheating. Validity evaluations, including discriminant validity and convergent validity, confirmed the validity of the scale. The average variance extracted (AVE) and composite reliability values also supported the scale’s convergent validity. The multidimensional concept of the PTC was supported by a four-factor solution consisting of 26 reliable and valid items.\n\nConclusion The findings of the study demonstrate that the scale has also provided sufficient evidence of convergent and discriminant validity. By establishing discriminant and convergent validity, as well as reliability, through different validation procedures, the study has provided strong evidence for the effectiveness of the PCS as an instrument for determining whether university students are likely to engage in cheating behavior.",
"keywords": [
"exam cheating",
"propensity to cheats",
"university students",
"confirmatory factor analysis",
"construct validity"
],
"content": "1. Introduction\n\nAcademic dishonesty is a broad term that encapsulates various detrimental behaviors within educational environments, such as plagiarism and falsification of information. Although difficult to define precisely (Lambert et al., 2003), academic dishonesty involves a variety of damaging activities, such as plagiarism or making false excuses (Yazici et al., 2011). The concept of academic cheating was initially described by Rich (1984) as deceitful actions related to coursework, including cheating on tests, exams, and assignments, along with activities like obtaining exams illegally, plagiarizing content, manipulating data, and tampering with library resources.\n\nAccording to Davis et al. (2009), academic cheating involves deceiving or defrauding another’s through misleading or dishonest actions. They emphasize that it entails students engaging in behaviors that trick instructors into believing that the academic work submitted is their original creation. Academic cheating can be defined as “intentionally unethical behaviour” (Von Dran et al., 2001, pp. 40) and “using deception (fraud) in academic work” (Cochran, 2016, pp. 814), both of which result in a breach of the defined rules and accepted standards, granting cheaters an unfair benefit over those who do not cheat (Dick et al., 2003). ensuring quality outcomes. In order to guarantee quality outcomes, student assessment should actually be seen as a complex and multifaceted activity that requires alignment, balance, and rigor (Joughin & Macdonald, 2004). Academic integrity is paramount to upholding the quality of education, and reducing academic fraud is essential for a thorough evaluation process.\n\nAcademic dishonesty by students, which this study defines as plagiarism and cheating on assignments and tests (Adesile et al., 2016; Ives et al., 2017; Ives and Nehrkorn, 2019; Jensen et al., 2002; Lin and Wen, 2007; Owunwanne et al., 2010), undermines the goals of higher education institutions. It compromises assessment validity since results cannot be generalized to represent trustworthy estimates of students’ grasp of course-work content (Bouville, 2010; Muñoz-García and Aviles-Herrera, 2014).\n\nThe topic of propensity to cheat (PTC) among students is a significant concern in higher education institutions. A student’s propensity is the likelihood that they will engage in a specific action or behavior. Propensity is defined in the literature as the tendency or predisposition to participate in a particular behavior, in this case, cheating. Cheating tendencies are the inclinations of an individual or a group of individuals to commit crimes prior to, during, or following an exam with the intention of unfairly benefiting from an unfair advantage over other students (Offor, 2009). Cheating propensity is defined as a tendency, disposition, or likelihood that a student may commit examination malpractice in light of these definitions. For the objectives of this study, understanding this broader concept of cheating propensity is essential for developing effective strategies to prevent academic misconduct.\n\nVarious studies indicate that academic dishonesty is more prevalent than ever, and actions need to be taken by universities to educate students as well as faculty members about academic integrity and ethical professionalism (Diego, 2017; Feday, 2017; Jepngetich et al., 2017; Mebratu, 2014; Nelson et al., 2012). According to studies, dishonest behavior that began in high school can continue in college, and similarly, college students who engage in academic dishonest behavior are more likely to engage in dishonest behavior outside of the classroom (Harding et al., 2004). This suggests that there is a chance that dishonest behavior will continue over time and in different circumstances.\n\nAcademic cheating is a widespread problem around the world, with high rates of cheating reported among students in many countries. In the United States, surveys have revealed that up to 86 percent of college students have engaged in dishonesty in the classroom (McCabe et al. 2006). Bernardi et al. (2008) conducted a study to compare the perspectives of students from industrialized countries on cheating behavior. They discovered that 51% of the people in the samples admitted to cheating. According to Yussof and Ismail (2018), high rates of Malaysian students have cheated, primarily in assignments and quizzes that carry a lower weight in the final grade and are subject to less supervision and punishment. In South Korea, Ahmed (2018) discovered that 65 percent of pupils misbehaved using electronic media, and 80 percent of students committed academic fraud.\n\nIn Africa, academic dishonesty is equally prevalent. According to Umar (2004), cheating on exams was almost a standard practice in Nigeria. According to Munachonga (2015), examination misconduct has become increasingly common in Ghana. This is mostly because candidates are afraid of failing, lack confidence, are lazy, don’t prepare well, and, most importantly, are unable to apply themselves to their studies. Munachonga (2015) noted that officials of the Test Council of Zambia, the nation’s supervisory organization for exams, have occasionally been involved in examination malpractices.\n\nWhen compared to various other studies carried out worldwide, the prevalence rate found in Ethiopia is high. Even though there is little to no evidence on the subject, cheating has from time to time increased in Ethiopia (Tefera & Kinde, 2009). Chala (2021) discovered that, with an incidence a rate ranging from 53 to 96 percent, academic dishonesty is a severe problem impacting university students in Ethiopia. Research conducted locally has, in one form or another, verified the growing epidemic of academic cheating in Ethiopian education at all levels (Feday, 2017; Hailu, 2015; Mebratu, 2014; Tefera & Kinde, 2010; Wondifraw, 2021). Furthermore, according to the Ethiopian Education Development Roadmap (2018–30), students frequently cheat on tests, and teachers are afraid that aggressive student evaluation may lead to an inaccurate assessment of their work and inflated grades (MoE, 2018).\n\nAcademic dishonesty can be justified in various ways in an academic setting. The majority of the time, in Ethiopia, the behaviors take the form of plagiarism and exam cheating (papers and assignments). To mention a few results of research done in the Ethiopian setting, Feday (2017) and Mebratu (2016) found that plagiarism in written work and exam cheating are the most common forms of academic dishonesty. Furthermore, a number of lecturers have expressed concern about the increased incidence of plagiarism, assignment, and exam cheating, which suggests that Ethiopia’s public universities agree with the researchers’ concerns based on their observations and teaching experience. In particular, some Hawassa and Wolkite Universities College of Science and Engineering students engage in academic dishonesty, according to the researchers’ experience from several years of teaching students in a course. Additionally, some students are opposing the growing practice of exam cheating and plagiarism in coursework. Based on our observations, a major contributing factor to exam cheating is a student’s lack of academic proficiency in a particular area. In this sense, the chance of earning a high cumulative grade point average is increased by cheating. Closing the gap and validating a scale that might possess the required psychometric properties to specify measurement accuracy was, thus, the primary objective of this work.\n\nNumerous measures have been developed to measure university students’ tendencies toward academic dishonesty, according to a review of previous studies on the subject. Academic cheating is a multidimensional issue that affects people all around the world (Imran & Nordin, 2013; Iberahim et al., 2013; Nazir & Aslam, 2010; Thomas, 2017; Tadesse & Getachew, 2010; Saidin & Isa, 2013; Yang et al., 2013). The academic practices survey is a two-dimensional construct with plagiarism (items related to written work) and cheating (items associated with class tests and exams), as discovered by Roig and DeTommaso (1995) and Ferrari (2005). Additionally, Adesile et al. (2016) developed a three-dimensional scale for measuring academic integrity that takes into account plagiarism, cheating, and research misconduct. Finally, in light of the above-mentioned differences in the dimensions of academic dishonesty, the dimensions of PTC that are the subject of this study are cheating on tests, assignments, research work (plagiarism), and mutilation/theft of library resources.\n\nThe main issue with this is the legitimacy of how the PTC is measured in a setting where academic dishonesty is common. Few studies have thus far particularly addressed the PTC, but none of these studies are known to have used a well-developed and validated questionnaire. More specifically, except for a brief mention of the reliability coefficient, not much is known about confirmatory component analysis (Adesile et al., 2016). However, as Imran and Nordin (2013) pointed out, the dimensionalities of most of the measures were not carefully examined, and there was little indication that they have meaningful psychometric properties. Moreover, discriminant validity refers to a scale’s ability to discern between the relevant concept and other related constructs. Because previous scales were unable to show this differentiation, there is confusion regarding interpretation (Bashir & Bala, 2018). By conducting validity and reliability tests on older scales, researchers can assess these difficulties and recommend additional research.\n\nTherefore, a valid and culturally reliable propensity to cheat scale (PCS) is needed. It is therefore necessary to develop, assess its dimensionality, and validate an instrument measuring the PTC constructs. In order to guarantee that psychological and behavioral constructsare suitably defined and evaluated, it is imperative that instruments undergo validation and evaluation (Hair et al., 2010). Hair et al. also recommended that researchers continuously confirm the validity and unidimensionality of their conceptions, even when employing instruments that are well accepted. Regarding this, the measure’s discriminant and convergent validity were allegedly determined using a Multimethods Multitraits (MMMT) investigation, but there was no solid evidence to support this claim.\n\nThe main reason for the emergence of this study is the absence of an instrument to measure the tendency for academic dishonesty in Ethiopian higher education institutions. Despite the researchers’ experience in the study field, no prior research has been done on the psychometric qualities and validity of the PCS employed by these institutions. Therefore, the researchers sought to address this gap in the literature by conducting a study to evaluate the psychometric properties of the PCS in the context of Ethiopian higher education institutions.\n\nTo achieve this, a confirmatory factor analysis (CFA) was conducted to determine the scale’s applicability and assess the convergent and discriminant validity of students’ propensity for academic fraud. This study utilized a sample of public university students in Ethiopia, where no previous research of this kind had been conducted. Therefore, this research sought to contribute to existing knowledge by examining the effectiveness of the PCS in measuring academic dishonesty tendencies among Ethiopian higher education students and addressing the research gap in this area.\n\nIn order to assess the convergent and discriminant validity of the scale, this study attempted to ascertain the construct validity of a locally developed PCS. The objective of this research was to assess the measurement model validity of the PCS among science and engineering students in order to add to the body of data supporting its construct validity. Analyze the PCS’s convergent and discriminant validity in particular.\n\nThe major focus of this study was on the latent construction of students’ propensity for academic misconduct in the higher education setting in Ethiopia, which was represented in four dimensions: (1) corresponding to cheating on tests and examinations, (2) cheating on assignments, (3) cheating on research work (plagiarism), and (4) theft and mutilation of library materials. The researchers concluded that it would be appropriate to validate the locally developed PCS in order to assess its convergent and discriminant validity. Two distinct research questions were formulated in order to achieve the research objectives:\n\n1. To what extent does the PCS demonstrate convergent validity?\n\n2. To what extent do the items in the instrument of PCS show discriminant validity?\n\n\n2. Methods\n\nIn Ethiopia’s public universities, this study was conducted among students studying Science and Engineering. The researchers carried out the factorial structure, exploratory factor analysis, and measuring tool reliability in the initial stage. In the current study, the researchers looked at the degree to which CFA on the same set of observations can support the findings from the EFA study.\n\nAccording to Clark and Creswell (2008, p. 58), a research design is the “procedures for collecting, analysing,interpreting, and reporting data inresearch studies.” It is the overarching strategy for linking theoretical research issues with relevant (and doable) empirical research. In other words, the study design determines how the necessary data will be collected, how it will be analysed, and how it will be used to address the research question (Grey, 2014). There are three different types of study designs that can be used: exploratory, descriptive, and explanatory (Robson, 1993). His classification system is based on the goals of the research field because each design has a distinct ultimate goal. By using an explanatory research design in this study, we aim to understand the relationship between students’ reported PTC and their academic self-concept and academic accomplishment through a quantitative approach. A correlational research methodology used for explanatory purposes allows the researchers to assess the degree of association between two or more variables. Additionally, using this style of research design enables the researcher to gather data all at once (Creswell, 2015).\n\nThe study focused on fourth-year science and engineering regular undergraduate students attending Ethiopia’s public universities. The researchers selected this specific group from the target population of first- to fifth-year science and engineering undergraduate students in the participating universities. The target population consisted of 6,524 students, including 4,901 males and 1,623 females.\n\nIn this study, the sample selection procedure was conducted in a systematic manner. First, three public universities, namely Hawassa University, Ambo University, and Wolkite University, were selected using the purposive sampling technique. These universities were chosen to represent both old and new public universities. Next, a purposive sample strategy was employed to select the colleges within the participating universities. Specifically, the colleges of Natural and Computational Science and Engineering/Institute of Technology were chosen. Following the selection of the colleges, departments were randomly chosen from among the selected colleges. This random selection ensured a diverse representation of departments within the chosen colleges. Finally, a simple random selection procedure was used to select students from the chosen departments for the study. This ensured that the sample of students was representative of the larger student population within the universities.\n\nThe researcher converted Gomez’s (2013) Sloven’s Formula into a formula to compute the sample size for this study. The sample size was determined using the following formula. The following is how this formula is laid out:\n\nWhere, N is the target population size\n\nn is the sample size and\n\ne is the level of precision (acceptable margin of error at 5% (95% confidence level), P = .5 are assumed for equation\n\nFor this study the target population (N=4120) then the required sample size is calculated as\n\nWhen selecting a sample size for the study, several criteria need to be considered. These include the size of the population, the level of confidence, the margin of error (confidence interval), the number of variables used in the study, the statistical analysis technique to be employed, as well as time, money, and effort constraints. In this regard, Ellen (2014) asserts that a formula must be employed to account for the margin of error and confidence level when a sample is drawn from a population. Further, research claims that Sloven’s formula should be used when there is little information available about how a population will behave (such as in the case of this study polling college students to assess their opinions and likelihood to cheat online), other than its size (Ellen, 2014; Kavai, 2014; Tanty & Rahayu, 2014; Abun & Cajindos, 2012). This equation enables the researcher to accurately sample the desired population (Ellen, 2014). It is thought reasonable to select a sample size using Slovin’s formula, which was developed in 1960. This is true in particular when there is uncertainty regarding the behavior of the population (Isip, 2014).\n\nOf the 550 students invited to participate in the study, only 500 completed the questionnaire correctly. The universities, their respective colleges, and the study participants are summarized in Table 1.\n\nThis study employed a self-administered questionnaire for the measurement of PTC by four first-order factors: mutilation of library materials, cheating on tests or exams, cheating on assignments, and cheating on research work. All of the dimensions and their subdomains have been constructed, and this study included the reliability and validity (convergent and discriminant validity) of the scale. Notion validity in this context refers to how well a scale’s items are suited to measuring a certain theoretical construct (DeVon et al., 2007; Kane, 2001). Discriminant and convergent validity are two fundamental features of construct validity, according to most arguments (Cronbach & Meehl, 1955; Campbell & Fiske, 1959; Pike, 1992, 2006). The construct validity of the PCS was then investigated in this study by examining both its convergent and discriminant validity.\n\nTo assess academic self-concept, Liu and Wang (2005) developed a scale consisting of 20 items. These items are designed to measure students’ confidence and motivation in their academic abilities within a university environment. Participants rated each item on a five-point Likert scale, ranging from strongly disagree (1) to stronglyagree (5). The internal consistency reliability of this scale is 0.85.\n\n2.4.1 Validation of the measures\n\nFollowing the pilot study validation of face validity, content validity, and reliability, more testing of other types of validity and reliability is necessary before they can be fully implemented and taken into account during the PCS validation process in this study on an adequate number of participants. Through CFAs and EFAs, the construct validity validation procedures as well as the dimensional structure of the PCS were assessed in terms of exploration, item reduction, confirmation, and validation.\n\nIn a validation study, 550 students from three public universities were given a questionnaire to determine their PTC and their perception of their academic self-concept. Out of the initial 550 participants, 500 students fully answered the PTC and academic self-concept items and were included in the analysis. Among these 500 students, there were 367 males and 133 females, with ages ranging from 18 to 40 years (M = 1.18, SD = .49). Additionally, 50 students who partially answered the items were disqualified from the study.\n\nPrior to data processing, the frequency distribution and the minimum and maximum scores for each item were used to verify that the database had been entered accurately. Additionally, each measure’s underlying assumptions for CFA were examined, and they were confirmed to be valid for the analysis.\n\nIn November 2022, data collection for this research began immediately following the enrolment of fourth-year students for the first semester of the academic year. The measures were translated into Amharic and back-translated by three translators from the English and psychology departments of Wolkite University to validate the instrument (PSC). Approval was obtained from each college dean before the commencement of data collection for this study. The college deans informed the department heads and instructors of the individual institutions about the study’s objectives. Subsequently, arrangements were made for the researchers and data collectors to recruit participants in the classroom. Teachers at the universities were tasked with informing and motivating students to participate in the study and scheduling times for the researchers to speak with them during regular class hours. Before delivering the questionnaires, the fourth-year students selected for the study provided their verbal informed consent.\n\nThe study began with a thorough briefing for the participants, which included the goal and objective of the research, the focus of the questionnaire, and the potential benefits of the study for society and individuals. The participants were then asked for their consent to participate voluntarily, with the assurance that they could withdraw at any time without consequences and that all information provided would be kept confidential. Following the briefing, the researchers distributed the Amharic revised version questionnaires to students at Hawassa University, Ambo University, and Wolkite University from November to January 2022 during regular class time.\n\nThe data processing procedures began by analyzing incomplete questionnaire responses and discarding any that were not complete. The remaining questionnaires were then coded and entered into a computer for further analysis. The data was cleaned to remove any errors that may have occurred during the coding process. Additional checks were conducted to ensure the accuracy of the data entry and measurement scales. The data was then examined for outliers, normality, skewness, and kurtosis to determine if it was at a normal level.\n\nCFA is another kind of measurement-related structural equation modeling (SEM) (Brown, 2015). CFA should be used to substantiate the connections made between the items and the corresponding factors. This gives metrics to evaluate how well the suggested theoretical model fits the collected data and allows these relationships to be fixed in the measurement model (Stevens, 2012). According to Brown (2015), CFA is therefore seen as a crucial instrument for validation in the social and behavioral sciences. Regarding this, structural equation modeling (SEM) with CFA was used to verify the measurement and structural model.\n\nThe Statistical Package for the Social Sciences (SPSS) and STATA 14 were used for the analysis of the data. Cronbach’s alpha was used to evaluate internal consistency and reliability. The convergent and discriminant validity of the PCS were also examined to evaluate construct validity. CFA was utilized to address research questions such as whether the sample’s data matched the established PTC measurement model.\n\nIn addition, research questions like how much the recently developed PCS demonstrates convergent validity were addressed using Composite Reliability (CR), Average Variance Extracted (AVE), Maximum Shared Squared Variance (MSV), and Average Shared Squared Variance (ASV). While the research question, such as how much the newly constructed PTC instrument demonstrates discriminant validity with other validated factors (the academic self-concept), was addressed using Pearson correlation analysis.\n\n\n3. Analysis and results\n\nData from the SPSS software version 25 was input and validated for missing data before being transferred to STATA Version 14 for CFA analysis. CFA was used to further validate the factorial structure of the PTC questionnaire that was initially identified through exploratory factor analysis (EFA) with a sample size of n = 550.\n\nTo analyze whether or not the established PTC measurement model fits to the data, CFA was used, and to analyze both convergent validity and discriminant validity, composite reliability (CR), average variance extracted (AVE), maximum shared squared variance (MSV), and average shared squared variance (ASV) were used.\n\nAfter the exploratory factor analysis conducted in Study 1, CFA is used to establish the data set’s factor structure. The exploration of factor structure (how variables link and are grouped based on inter-variable correlations) in the CFA confirms the factor structure that was extracted in the exploratory factor analysis (EFA) (Brown, 2015). To evaluate model parameters and fit indices across the clustering of independent variables, a CFA was also carried out for all data sets to look into the general concept validity (Chuang, Weng, & Huang, 2015).\n\nBoth the first-order (measurement model) and the second-order (structural model) were used to validate the model. The findings, as shown in Figure 1 and Table 1, strongly support the measurement of PTC using four first-order factors: cheating on tests or examinations, cheating on assignments, cheating on research work, and mutilation of library materials, with a total of 26 items based on the PSC. These items were designed to elicit responses from university students regarding how they perceived their academic cheating.\n\nThe measurement model was put to the test, and then the structural model was examined using the standards outlined in the literature (see Hair et al., 2016). The measurement models assess the fit of the data to the model and the link between the latent variable and its indicators (Henseler et al., 2009). The first-order CFA model has been developed to measure the relationships between the four dimensions (cheating on tests, cheating on assignments, cheating on research work, and theft and mutilation of library materials) and the twenty-six associated items that fit the empirical data well. The measurement models for the unobservable (latent) variables were generated and validated using the CFA approach in this study. Because the observed variables of the PTC subscales were determined in advance based on a review of the literature and interviews with experts, a CFA was used to assess the link between cheating on tests, cheating on assignments, cheating on research work, and theft and mutilation of library materials and each of their observed variables in order to develop a measurement model that fit the empirical data well. Figure 1 below shows the measurement models for the four-factor PTC. Figure 1 is available in the data repository (Gizaw, 2024).\n\nMultiple fit indices were employed to assess the appropriateness of the CFA model’s fit to the data, including the χ2/df ratio, Tucker Lewis Index (TLI), comparative fit index (CFI), and root mean square error of approximation (RMSEA). The goodness-of-fit indices of the CFA model for the PCS are shown in Table 2. Despite the fact that the chi-square statistic has a significant value (χ2/df = 3.877, p =.000), alternative fit indices are encouraging due to the highly sensitive nature of this statistic to large samples (Bentler & Bonett, 1980; Stevens, 2002). The CFA results demonstrate that the model had fit statistics such as RMSEA = 0.076, RMR = 0.045, TLI = 0.907, and CFI = 0.916. According to the literature, the chi-square value of less than 5 is acceptable, and less than 3 is good (Marsh & Hocevar, 1985). Hu and Bentler (1999) and Browne and Cudeck (1992) proposed (RMSEA less than .08, RMR less than .05, TLI and CFI greater than .90) as the recommended values for this fit statistic. Based on the indices obtained after CFA, the results indicated that each dimension’s factor model fit each dimension well. Finally, the coefficient of determination for the entire model is extremely high (CD = 1.000).\n\nIt is required to move on to the structural model after developing the measurement model. A structural model explains how the many constructs in a model relate to one another. The four measurement models become structural models in the second-order CFA model by linking them collectively or through PTC, as shown below. In order to validate the four-factor structure developed by the exploratory factor analysis (EFA), a second-order CFA was applied. The next phase in structural equation modeling (SEM) analysis is to examine the goodness of fit of the full structural equation model and determine if an acceptable full structural model is obtained after acquiring an acceptable measurement model that fits the empirical data. A set of goodness-of-fit analyses was carried out for this purpose.\n\nFigure 2 is shows the factor distributions and values obtained from the second-order CFA model. Figure 2 available in the data repository (Gizaw, 2024).\n\nTo examine the relationships, a structural equation model created with STATA 14 was utilized. A good fitting model is acceptable if the CMIN/df value is less than 5; the Tucker Lewis Index (TLI) (Tucker and Lewis, 1973); and the confirmatory fit index (CFI) (Bentler, 1990) is greater than 0.90 (Hair et al., 2010). In addition, an adequate fitting model was accepted if the standardized Root-Mean Square Residual (SRMR) estimated by STATA was less than 0.05 and the Root Mean Square Error of Approximation (RMSEA) was between 0.05 and 0.08 (Hair et al., 2010). The alternative fit indices are encouraging due to the sensitivity of the chi-square statistic to sample size: χ2/df = 3.966, CFI = 0.913, TLI = 0.904, RMSEA = 0.077 and RMR = 0.049. The chi-square statistic has a significant value, χ2 (295) = 1170.069, p. <000. In this regard, the second-order CFA model was suitable since all of the indices met the threshold values of the requirements and because their values were comparable to those of the first-order CFA model. Finally, the total model’s coefficient of determination (CD = 0.912) is very high.\n\nThe study used CFA to explore the underlying latent variable structure of the PCS from the same sample on which the EFA was administered in order to evaluate the goodness of fit of the four-factor structure produced from the EFA.\n\nTable 3 and Figure 2 demonstrate that each factor loading was significant at p<.05. Additionally, the results of the standardized factor loading coefficients showed that the subscales measuring cheating on exams and tests ranged from .75 to .86, the subscales measuring cheating on assignments and research work from .59 to .72, and the subscale measuring theft and mutilation of library materials from .77 to .92.\n\n* p < 0.05.\n\nFurthermore, the squared multiple correlation coefficients also provide the coefficient of determination (R2), which illustrates the extent to which a factor may account for the variance in an item. In this regard, the COT5 item has the highest R2 (.74), meaning that the latent variable test-cheating accounts for 74% of the variation in the COT5 item.\n\nThe model was able to explain 64 percent, 52 percent, 79 percent, and 79 percent, respectively, of the factors related to cheating on tests, cheating on assignments, cheating on research work, and theft and mutilation of library materials (Table 3 below). The results showed that, after exam cheating, the two most important factors were theft of library items and exam cheating. Cheating on exams, assignments, research work, and mutilating library materials collectively account for 91% of the variance in the PTC, as indicated by the squared multiple correlation for the PTC of 0.91 (see Figure 2).\n\n\n4. Validity assessment\n\nAnalyzing both convergent validity and discriminant validity allows for the examination of construct validity. The construct validity of a scale is examined after its dimensionality and reliability have been confirmed to be appropriate. The CFA also considered the validity of both convergent and divergent findings.\n\nIn this study, the PTC measure was evaluated for convergent validity by examining the internal consistency of the indicators measuring the same construct. In Bagozzi’s (1981) definition of convergent validity, the emphasis is on the internal consistency of indicators measuring the same construct. Researchers utilized reliability measures as one of the criteria to assess convergent validity (Fornell & Larcker, 1981). However, they recognized that evaluating convergent validity just on the basis of reliability is insufficient. To further assess convergent validity, a measurement model was estimated in which all indicators were related to the constructs they were intended to measure and not directly related to constructs they were not intended to measure (Fornell & Larcker, 1981; Hair et al., 2009). All indicators converge well on their own construct when the predicted measurement model sufficiently matches the data. Since model fit does not ensure measurement quality, researchers have argued that an appropriate model fit is insufficient to support convergent validity (Fornell & Larcker, 1981). As a result, additional criteria have been proposed to ensure that the indicators truly measure the intended construct.\n\nThe standardized factor loading, extracted average variance (AVE), and composite reliability (CR) tests were also used to assess convergent validity. Numerous studies have proposed evaluating convergent validity by looking at the statistical significance of standardized factor loadings (e.g., Dunn et al., 1994). For instance, Hair et al. (2009) claimed that all standardized factor loadings should be at least 0.5 and, ideally, at least 0.7, while Stevens (2002) suggested that the value of a factor loading should be more than 0.4 for interpretation purposes. The factor loadings were all greater than 0.59, and some loadings were greater than 0.70 (see Table 3). Some studies have utilized the Fornell and Larcker (1981) criterion for evaluating convergent validity in addition to looking at the standardized factor loadings (for instance, Yu et al., 2021; Zahoor et al., 2022). According to Fornell and Larcker (1981), convergent validity is demonstrated when a latent construct explains at least half of the variance in the indicators it is related to. To indicate the average amount of variance that a construct explains in its indicators relative to the sum variance of its indicators, they suggested using the average variance extracted (AVE).\n\nThe value of AVE for the PTC subscale equals the sum of the average square of factor loadings across all of its indicators divided by the number of items. In order to determine whether the items logged under each facet or domain were estimating the same concept, composite reliability (CR) values of 0.7 or higher and average variance extracted (AVE) values of 0.5 or greater were employed (Hair et al., 2019). Convergent validity, according to Hair et al. (2009), is seen when the CR is greater than the AVE and the AVE is greater than 0.5.\n\nAccording to the table, all of the AVE and the items’ total standardized factor loading were both greater than 0.59, which is a sign of good convergent validity (Hair, Sarstedt, Ringle, & Gudergan, 2017). For this reason, the value of each PTC subscale’s composite reliability was higher than the value of the average variance extracted (see Table 4). The cheating on research work and cheating on assignments variables’ AVE values (0.37 and 0.38) are below but around the suggested cutoff limit of 0.50 (Malhotra, 2019), as shown in Table 4. The construct has acceptable convergent validity if AVE is less than 0.5 but the composite reliability is greater than 0.6 (Fornell & Larcker, 1981). Exam cheating and library material theft value components show acceptable AVEs of 0.56 and 0.61, respectively, exceeding the 0.5 cutoff and confirming the convergence validity of their latent construct.\n\nConvergent validity is also demonstrated by the fact that the Maximum Shared Variance for all three variables is less than the pertinent Average Variance Extracted. Our variables have a high level of internal consistency, as seen by the table’s composite reliability of all factors, which is greater than 0.70 (Gefen et al., 2000).\n\nThe first condition for discriminant validity is establishing convergent validity (Bagozzi, 1981). This means ensuring that a construct is sufficiently represented by its indicators.\n\nThe objective of this stage was to establish further evidence based on relationships to other variables, i.e., evidence pertaining to the construct validity of the instrument (Balkin, 2017). Construct validity is a vital aspect of validating a tool, as it includes establishing the theoretical link between the variables being measured and other relevant constructs (DeVellis, 2016). One of the five main forms of validity evidence that focuses on showing connections between assessment scores and crucial criteria is evidence based on linkages to other variables (AERA, APA, & NCME, 2014). The strength and direction of the association between theoretically pertinent constructs are determined using discriminant validity, a kind of construct validity (DeVellis, 2016). The degree to which there are insignificant correlations between measures of theoretically unrelated constructs is referred to as discriminant validity. Discriminant validity is demonstrated, in accordance with Gefen and Straub (2005), “when each measurement item weakly correlates with another construct other than those to which it is theoretically associated.”\n\nDiscriminant validity is conducted to ensure that the PCS measures a construct that is distinct from other constructs. Scales that measure theoretically unrelated constructs should, according to discriminant validity, have a low correlation (DeVellis, 2003; DeVon et al., 2007). Discriminant validity testing is done primarily to demonstrate how different an item or set of items is from others in this study. In other words, the objective of this study is to demonstrate low correlations between items measuring various constructs or variables. This study examined the association between the PCS and other established measures, such as the academic self-concept scale. By assessing these associations, the researchers purpose to reveal the unique contribution of the PCS in measuring PTC in academic settings.\n\nThe perceived propensity of students to cheat and their academic self-concept were examined using a bivariate correlational analysis. Bivariate correlation was also used to assess the link between academic achievement and students’ perceived PTC. For the purposes of data analysis, the continuous composite scores on all scales were regarded as interval levels.\n\nBased on a review of the literature, it was predicted that there would be little link between the PTC and academic self-concept. Table 5 displays the relationships between the PTC subscales (MOL, COT, COR, and COA) and academic self-concept (ASC), with the bolded red items denoting discriminant validity. The correlation between the ASC and the subscales (MOL, COT, COR, and COA, respectively) was found to be lower than the correlation between the items of the same construct, such as the respective PTC subscales for MOL, COT, COR, and COA were.678,.741,.586,.520,.571, and.578. This indicates a strong link between items on the PTC subscale alone, but weak correlations between those same items and academic self-concept. To sum up, the results indicate that there is a low relationship between the PTC and academic self-concept, as expected.\n\n** p < 0.01.\n\n* p < 0.05.\n\nFurthermore, research on cheating has shown that there is only a weak negative correlation (Cizek, 1999) between cheating and grade point average (GPA). Higher GPA students are less likely to report or cheat, but students with lower grades are more likely to do both. For this reason, Table 6 displays that the correlations between the students’ cumulative grade point averages (CGPA) and their PTC subscales (MOL, COT, COR, and COA) are lower compared to the correlations between the items of the same construct (PTC subscales). This indicates discriminant validity, which is represented by the red-bolded items, as the relationships between the CGPA and the PTC subscales are not as strong as the relationships within the PTC subscales themselves. Table 6 indicates that there is a lower negative relationship between the CGPA and the MOL, COT, COR, and COA subscales than there is between the items of the same construct, such as the PTC subscales, which have correlations of .678, .741, .586, .520, .571, and .578 (MOL, COT, COR, and COA, respectively).\n\n** p < 0.01.\n\n* p < 0.05.\n\nIn short, the PTC and academic self-concept showed a positive, although weak, relationship, indicating discriminant validity. In addition to this, the PCS’s discriminant validity is supported by the low, negative correlations between students’ academic achievement and PTC.\n\n\n5. Discussion\n\nA CFA was conducted for this purpose in order to strengthen the validity of the suggested model of PTC and validate the 4-factor solution obtained from the EFA. Several model fit indices were used to assess the goodness of fit of the CFA model. Brown (2015) divided model fit indices into three categories as a result: “absolute fit, fit adjusting for model parsimony, and comparative or incremental fit” (p. 71). According to Brown (2015), absolute fit indices, which include the chi-square statistic (χ2) and the standardized root mean square residual (SRMR) indices, evaluate model fit at an absolute level. Collier (2020) offers a relative chi-square test, which is the chi-square value divided by the degrees of freedom (χ2/df), as a better method to utilize because the chi-square statistic is more sensitive to sample size. According to Collier (2020), a relative chi-square value (χ2/df) that is considered acceptable may range from 3 to 5. Any number below 3 denotes an excellent model fit, while values between 3 and 5 demonstrate an acceptable level. As a result, the first-order CFA model’s outcomes demonstrated that it had a chi-square statistic (χ2 = 3.877, p = .000).\n\nParsimony correction indices, sometimes also referred to as absolute fit indices, are the second category of model fit indices (Brown, 2015). The root-mean-square error of approximation (RMSEA) is the most widely used and advised index in this area, according to Brown (2015). The RMSEA is referred to as an error of approximation index since it measures how well a model matches the population (Brown, 2015). The purpose of this study is not to determine whether the model applies to the population exactly. The RMSEA is hence “sensitive to the number of model parameters” but “relatively insensitive to sample size” (Brown, 2015, p. 71). Comparative fit indices, which are also referred to as incremental fit indices and assess the fit of a user-specified solution against a nested baseline model, are the third category of model fit indices, according to Brown’s (2015) taxonomy. The CFI and TLI are the most popular and suggested indices in this category, according to Brown (2015).\n\nIn this study, the models were assessed to determine if they accurately reflected the data using a number of model fit indices. The measurement model outputs of the first-order CFA model-based fit indices in this analysis were CFI = .916, TLI = 0.907, SRMR = .045, and RMSEA = .076; these values suggest that the model had a good fit to the observed data (χ2/df = 3.88, p = .000). In regard to this, the CFI value was 0.92 indicated a satisfactory fit, whereas CFI values are 0.90 and higher as considered acceptable (Kline, 2023; Thompson, 2004). RMSEA = .077, CFI = .913, RMR = .049, and TLI = .904 are the results of the second-order CFA model run on the scale structure consisting of four factors and 26 items (χ2/df = 3.966, p = .000). The PCS has a valid and reliable factor structure as a result of the structural model’s adequate fit to the sample data. Thus, both the structural and measurement models demonstrated good fit to the empirical data, indicating that the PCS has a valid and reliable factor structure.\n\nDiscriminant validity and convergent validity were used to investigate construct validity. Convergent validity is usually examined first, followed by discriminant validity. According to Collier (2020), this type of construct validity describes the extent to which all indicators of a certain construct are measuring the same thing (construct) that they are supposed to measure. “Evidence that different indicators of theoretically similar or overlapping constructs are strongly interrelated” (Brown, 2015, p. 2) serves as the basis for this determination.\n\nThe term “convergent validity” refers to the closely connected variables inside a single component (Kaplan & Saccuzzo, 1993). The convergent validity was investigated using factor loading, average variance extracted (AVE), and composite reliability (CR) (Hair et al., 2017). All factor loadings were higher than 0.59, as shown in the result section. The standard for an item to be included within a factor is having factor loads above .40 (DeVellis, 2014; Hair, 2009). In addition, if the factor loading was greater than 0.5, it was considered acceptable (Hidayat et al., 2018). The AVE abbreviation stands for the “average of the squared standardized pattern coefficients for indicators that depend on the same factor but are specified to measure no other factors” (Kline, 2023, p. 313). All CR was greater than.85, while AVE was over 0.37.\n\nAccordingly, Hair et al. (2010) proposed that convergent validity is achieved when composite reliability is more than average variance extracted (AVE), with both values exceeding .70 and .50, respectively. The AVE values for plagiarism and theft of library resources are 0.56 and 0.61, respectively, which are both higher than the cutoff value of 0.5 and indicate the convergence validity of their latent construct. However, the AVE values for plagiarism in research work and cheating on assignments are slightly below but near the recommended cutoff of 0.50, at 0.37 and 0.38 (Malhotra, 2019). The construct has adequate convergent validity if the mean variance is less than 0.5 and the composite reliability is greater than 0.6 (Fornell & Larcker, 1981). In light of this, all subscales in this study satisfied the convergent validity of the constructs (Fornell & Larcker, 1981). Therefore, these results demonstrate that the scale has achieved convergent validity.\n\nThe test of discriminant validity in this study showed that the PCS, academic self-concept, and CGPA are distinct constructs, as evidenced by the low correlations between them. As demonstrated by Gholami et al. (2013), discriminant validity is reached when a construct measures how many indicators are used to indicate only one construct while being genuinely unique from the other constructs. Two latent variables representing various theoretical concepts are statistically different when they have discriminant validity.\n\nIn this study, the correlations between the PCS, academic self-concept, and CGPA were tested. A low negative correlation between the CGPA and the PCS would be indicative of discriminant validity. Similarly, it was supposed that evidence of discriminant validity would come from a low correlation between academic self-concept and PCS. The correlation between the PTC subscale, academic self-concept, and CGPA is less than 0.12, as indicated in the results section, indicating that discriminant validity was demonstrated. The findings of this study align with previous research suggesting that Comas-Forgas and Sureda-Negre (2010) suggest that students who struggle academically are more likely to commit plagiarism. As one of the most significant types of PTC, plagiarism, this evidence can be used to demonstrate the validity of the discriminant. Similarly, studies have indicated that students who perform well academically or have higher cumulative grade point averages are less likely to plagiarize (Guo, 2011).\n\nBased on the CFA’s findings, the updated versions of the PCS’s four subscales had high support for the scale’s reliability, discriminant validity, and convergent validity. This study provides evidence that the PCS is a valuable instrument for measuring different aspects of PTC.\n\n\n6. Conclusions and practical implications\n\nIn this study, a validated assessment scale known as the student’s PCS was developed. This scale may be beneficial to assess students’ intent to cheat and to enable further intervention for the widespread practice of cheating in universities. On the basis of examining the fit index values obtained from the first-order CFA, the scale can be considered to have adequate fit values (χ2/df = 3.877, RMSEA = .076, CFI = .916, SRMR = .045) and TLI = 0.907, whereas in the second-order CFA, the scale can be considered to have adequate fit values (χ2/df = 3.966, CFI = 0.913, TLI = 0.904, RMSEA = 0.077, and RMR = 0.049).\n\nIn this study, the convergent and discriminant validity of the four PCS factors’ were examined. Convergent validity was assessed based on the factor loading, extracted average variance (AVE), and composite reliability (CR) values of the scale. The AVE values for the factors were as follows: The first factor had a value of 0.61, the second factor had a value of 0.56, the third factor had a value of 0.38, and the fourth factor had a value of 0.37, the CR values were .92, .88, .78, and .80 for the first, second, third, and fourth factors respectively. The scale demonstrated acceptable convergent validity based on these results.\n\nDiscriminant validity was assessed by exploring the relationship between the PTC subscale scores, academic self-concept, and grade point average (GPA). In connection to this, the correlation coefficients between the PTC subscales, students’ academic self-concept, and cumulative grade point average (CGPA) were, respectively, (.678, .741, .586, .520, .571 & .578), (.067, .051, .088 & .121), and (.004, .043, .106 & .055). It was observed that there were low correlations between the PTC subscale items, academic self-concept, and GPA. However, there were significant inter-factor correlations within the PTC subscale items.\n\nBased on the findings, the discriminant validity of the PCS was confirmed. Post-analysis, it is clear that the scale’s convergent and discriminant validity were both supported by the data.\n\nThe reliability of the scale was examined using Cronbach’s alpha reliability coefficients. Cronbach’s alpha coefficients were calculated for the scale (total score) and subscales of the PTC in order to evaluate the internal consistency. The scale has a high level of internal consistency, as seen by its overall Cronbach’s alpha (.96) (Field, 2013). The PTC subscales of cheating on tests, cheating on assignments, cheating on research, and theft and mutilation of library materials all had reliability analyses that were, respectively, .93, .85, .90, and .96.\n\nAll four factors of PTC have demonstrated satisfactory validity in terms of convergent validity, discriminant validity, and model fit in the final PCS. A high degree of estimation reliability has also been demonstrated by the PCS.\n\nIn conclusion, this study has established the multidimensional character of the concept of PTC. The final PCS now includes 26 and 4 reliable and valid items and factors that may be used to evaluate various PTC aspects.\n\nAccording to the study’s practical implications, academic measurement and evaluation researchers and practitioners can measure the extent of four common PTC types in Ethiopian higher education contexts, especially among university students, using the PCS. This could help professionals accurately assess issues of academic misconduct related to PTC. The PCS was designed and validated because of the study’s contributions to our understanding of academic and professional environments, cheating behavior, and prevention and intervention measures.\n\n\n7. Limitations and recommendations for future research\n\nAlthough this study offers academics, practitioners, and students working in the measuring and assessment sector practical advantages, it also has significant limitations that future researchers should address,\n\nEthiopian public universities serve as the setting for the development and validation of this PCS. Therefore, we suggest researchers at other Ethiopian private universities to examine the validity and reliability of our instrument in relation to their respective academic environments.\n\nMoreover, the purpose of the recently developed and validated instrument was initially to assess a student’s PTC during assessments or examinations. Unfortunately, the study did not include this demographic data (family status and socioeconomic status). It is believed that these factors may have an influence on an individual’s PTC. Lastly, in order to measure PTC effectively, researchers and educators need more valid and reliable tools to study and assess PTC.\n\n\nConsent of participants\n\nTo begin the process of obtaining participants’ willingness to participate in the study, the researchers introduced themselves and provided further explanations about the study. This included details about the participants’ degree of involvement, the objective of the study, the focus of the questionnaire, and the potential benefits of the research for society and individuals.\n\nAfter receiving verbal consent from the participants, the researchers explained that participation was voluntary. Participants were informed that they could choose to leave the study at any time without facing any penalties or losing any advantages. Additionally, participants were assured that all information provided would be kept confidential.\n\nFollowing this verbal consent, written informed consent was then obtained from all participants. The written consent form is available in the data repository (Gizaw, 2024). This process ensured that participants understood and agreed to their participation in the study, while also emphasizing the importance of confidentiality and voluntary participation. Consent of participants available in the data repository (Gizaw, 2024).\n\nThe study was conducted in compliance with pertinent standards and regulations and was approved by Hawassa University. After the PhD dissertation proposal was approved and ethical clearance was obtained from Hawassa University’s Office of Vice President for Research and Technology Transfer (VPRTT), the study was carried out. The School of Teacher Education granted approval in this regard on 09/02/2014, with reference number COE-REC/017/24. The data repository contains the ethical approval certificate (Gizaw, 2024).",
"appendix": "Data availability\n\nOSF: Propensity to Cheat and Academic Self-concept. https://doi.org/10.17605/OSF.IO/7G9JN (Gizaw, 2024)\n\nThis project comprises the following:\n\n\n\n• Figure 1. JPEG output of the measurement model for Latent Variable \"Four-Factor of PTC\" and Observed Indicators\n\n• Figure 2. JPEG output of the Structural Model for the Students’ Propensity to Cheat.\n\n• SPSS data.xlsx\n\nOSF: Data and materials for propensity to cheat scale.\n\nThis project comprises the following:\n\n- Questionnaire.docx\n\n- Informed Consent.docx\n\n- Participation Consent Form\n\n- Permission Certificate\n\n- Ethical Approval Certificate\n\n- Acknowledgement Certifiicate\n\nData are accessible under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nAcknowledgements\n\nThe authors of this article would like to express their gratitude to the Hawassa University, Ambo University, and Wolkite University students who volunteered their time and effort to fill out questionnaire. Additionally, we would like to thank the University of Hawassa for its coordination of this study. 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J 2012; 1(3): 68–74.\n\nOffor TD: Psycho-social variables and test-taking behaviour of students in Nigeria universities. Unpublished PhD dissertation. University of Calabar, Nigeria; 2009.\n\nOwunwanne D, Rustagi N, Dada R: Students perceptions of cheating and plagiarism in higher institutions. Journal of College Teaching & Learning (TLC). 2010; 7(11). Publisher Full Text\n\nPike GR: The components of construct validity: A comparison of two measures of general education outcomes. J. Gen. Educ. 1992; 41: 130–159.\n\nPike GR: The dependability of NSSE scalelets for college-and department-level assessment. Res. High. Educ. 2006; 47: 177–195. Publisher Full Text\n\nRich JM: Professional ethics in education. 2600 South First Street, Springfield, IL 62717: Charles C Thomas, Publisher; 1984.\n\nRobson C: Real world research-a resource for social scientists and practitioner-researchers.1993.\n\nRoig M, DeTommaso L: Are college cheating and plagiarism related to academic procrastination? Psychol. Rep. 1995; 77(2): 691–698. Publisher Full Text\n\nSaidin N, Isa N: Investigating academic dishonesty among language teacher trainees: The Why and How of Cheating. Procedia Soc. Behav. Sci. 2013; 90: 522–529. Publisher Full Text\n\nStevens J: Applied multivariate statistics for the social sciences. Mahwah, NJ: Lawrence Erlbaum Associates; 2002; vol. 4. .\n\nStevens JP: Applied multivariate statistics for the social sciences :Routledge; 2012. Publisher Full Text\n\nTadesse T, Getachew K: An exploration of undergraduate students’ self-reported academic dishonesty at Addis Ababa and Jimma Universities. Ethiop. J. Educ. Sci. 2010; 5(2): 77–99.\n\nTanty H, Rahayu A: Data Monitoring of Student Attendance at Bina Nusantara University Using Control Charts.2014.\n\nTefera T, Kinde G: Faculties’ Perception and Responses to Academic Dishonesty of Undergraduate Students in Education.Business and Economics Ethiop. J. Educ. Sc.2009; 4, No. 2.\n\nThomas D: Factors that explain academic dishonesty among university students in Thailand. Ethics Behav. 2017; 27(2): 140–154. Publisher Full Text\n\nThompson B: Exploratory and confirmatory factor analysis: Understanding concepts and applications. Washington, DC: 2004; vol. 10694; p. 3.\n\nTucker LR, Lewis C: A reliability coefficient for maximum likelihood factor analysis. Psychometrika. 1973; 38(1): 1–10. Publisher Full Text\n\nUmar E: The Menace called Examination Malpractice. News Watch Magazine. 2004 1st July.\n\nVon Dran GM, Callahan ES, Taylor HV: Can students’ academic integrity be improved? Attitudes and behaviors before and after implementation of an academic integrity policy. Teach. Bus. Ethics. 2001; 5: 35–58. Publisher Full Text\n\nWondifraw D: Academic cheating in Ethiopian secondary schools: Prevalence, perceived severity, and justifications. Cogent Educ. 2021; 8(1): 1–16. Publisher Full Text\n\nYang SC, Huang CL, Chen AS: An investigation of college students’ perceptions of academic dishonesty, reasons for dishonesty, achievement goals, and willingness to report dishonest behavior. Ethics Behav. 2013; 23(6): 501–522. Publisher Full Text\n\nYazici A, Yazici S, Erdem MS: Faculty and student perceptions on college cheating: Evidence from Turkey. Educ. Stud. 2011; 37(2): 221–231. Publisher Full Text\n\nYu M, Lin H, Wang GG, et al.: Is too much as bad as too little? The S-curve relationship between corporate philanthropy and employee performance. Asia Pac. J. Manag. 2021. Publisher Full Text\n\nYussof SH, Ismail S: Academic dishonesty among accounting students in Malaysia. Management & Accounting Review (MAR). 2018; 17(1): 19–46. Publisher Full Text\n\nZahoor N, Khan H, Khan Z, et al.: Responsible innovation in emerging markets’ SMEs: The role of alliance learning and absorptive capacity. Asia Pac. J. Manag. 2022. Publisher Full Text"
}
|
[
{
"id": "328802",
"date": "28 Oct 2024",
"name": "Nwabugo Ngozi Agu",
"expertise": [
"Reviewer Expertise Educational evaluation and research"
],
"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\nPaper Title: Confirmatory Factor Analysis and Propensity to Cheat Scale Validation in the Ethiopian Public Higher Education Institutions\nReviewers’ Comments Topic\n\nThe topic was not able to show the direction the authors intended to go. This might have been responsible for the inconsistencies in the focus of the study. ‘Propensity to cheat’ appears to be very broad. The specific group whose propensity to cheat will be measured by the instrument being developed is not specified. It could be propensity to cheat by teachers, students, or school administrators. It would have been better for this instrument to be titled – ‘Students’ Propensity to Cheat Scale’ so that the reader knows that the scale is for assessing students. 1.1 Background\n\nThe researchers in the Background spent much time on academic cheating and academic dishonesty and little time on propensity to cheat which is the central construct in the study, and was not even able to link propensity to cheat to the two terms. As in the case of the topic, the background centered on academic cheating, academic dishonesty and propensity to cheat; not specifically in respect of students, which was the concern of the present study.\n\nIn the last sentence of the last paragraph under background, the researchers created the impression that cheating tendency is always in respect of examinations, for example, they credited to Offor (2009) as saying that “cheating tendencies are the inclination of an individual or group of individuals to commit crimes prior to, during or following an exam with the intention of unfairly benefiting from an unfair advantage over other students”. That definition or explanation will hold if one is talking of students’ cheating tendency. Cheating tendencies can apply in situations outside examination. The same thing applies to the next sentence where the authors try to define cheating propensity. It is, therefore, suggested that these sentences should be expunged. 1.2 Prevalence and Academic Dishonesty\n\nSome expressions in the last paragraph in this section makes the reader uncomfortable. One of the sentences reads- “Furthermore, a number of lecturers have expressed concern about the increased incidence of plagiarism, assignment and exam cheating which suggest that Ethiopian’s public universities agree with the researchers’ concern based on their observation and teaching experience.” The message conveyed here is not understandable. The next sentence reads – “Additionally, some students are opposing the growing practice of exam cheating and plagiarism in course work”. The last sentence talks of closing the gap. The gap in question is not known.\n\n1.3 Problem Statement\n\nIn line five the phrase- “Academic practices survey” suddenly appeared. It had no link with what was said earlier. If the researchers had indicated that it was one of those numerous measures that had previously been developed, that would be more understandable.\n\nThe second paragraph of this section is not logical. The sentences there do not seem to link with each other, the researchers were probably trying to provide justification for engaging in the development of PCS. This was poorly done. The opening sentence of the paragraph started with: “The main issue with this is the…” The question is - main issue with what? The second sentence talked of few studies that had addressed PTC. The authors should have cited some of those few studies. In that same second paragraph, one was uncomfortable with the way discriminant validity was brought into the discourse. How will absence of discriminant validity give rise to confusion in interpretation? The last sentence of this paragraph which reads – “By conducting validity and reliability tests on older scales….” should be expunged.\n\nThere is inconsistency in paragraph four which starts with the main reason for emergence of this study. One does not know whether the researchers set out to validate or develop and validate an instrument.\n\nParagraph five, which starts with – “To achieve this…,” - should be taken to the methods section in this article. After going through the introduction section of this paper, the reader should be able to understand the “what” and “why” of the study. This was not the case. As regards the “what” of the study, one had difficulty in understanding the general purpose. Was it aimed at simply validating an instrument or developing and validating an instrument? Whichever of them is the case determines what are expected in the other sections of the paper. The researchers were inconsistent regarding what should be the general purpose of the study. From the topic, it was to validate an instrument; from the last sentence in the background, it was to validate an instrument; from the abstract, it was to develop and validate an instrument; from the section on statement of problem, it was to develop and validate an instrument; the first paragraph under research questions indicated that the purpose was to validate an instrument while the second paragraph talked of constructing an instrument. There was, therefore, a lot of inconsistencies regarding the general purpose. The authors need to be specific in this regard. Their position will guard one in assessing the other sections of the paper.\n\nAs regards the “why” of this study, the researchers have not convincingly justified the need for the study. Of course, the “why” will depend on the “what”. In short, the logic of presentation in the introductory section of the paper lacks flow of discourse. 1.4 Research Questions\n\nThe first paragraph should appear somewhere as the general purpose of the study, rather than under research questions. Note, however, that the general purpose had earlier been queried in the last section.\n\n‘The dimensions’ in paragraph two should be taken to the section where the instrument was described. 2.0 Methods\n\nThe introductory statement immediately after methods should be expunged. 2.1 Research Design\n\nIn this section, the researchers were primarily expected to state the design that was used, brief explanation of the design and the justification for choosing the design. The researchers needed to let the reader know that explanatory research design was used, before proceeding to state the goals for using it. 2.3 Sample and Sampling Procedure\n\nThe researchers should have informed the reader of the sample size before proceeding to describe the sampling procedure. The description of sampling procedure was very poor. From the way it was described, it is difficult for any person to replicate it. From how many universities were the three universities selected? The researchers stated that purposive sampling was used to select two Colleges. What was the purpose? How many Departments were sampled from the Colleges? Check the e2 in the formula for sample size. Should it not be e2 (e squared)? There is no small “n” in the formula. Should the population indicated after the formula not be 6524 instead of 4120?\n\nThe contents of Table 1 are not clear. The sample size of 550 or 500 is not seen in the table. 2.4 Research Instrument\n\nThe researchers were supposed to describe the instrument (s) that was (where) used for the study. That was not done. The name of the first instrument was not even mentioned. Academic self-concept emerged from nowhere. The academic self-concept instrument was not even described. Rather, the researchers simply stated that Liu and Wang (2005) developed an instrument. The instrument for this study has, therefore not been described. Note that there was no justification for the introduction of academic self-concept instrument. 2.4.1 Validation of the Measures\n\nThe researchers did not communicate in the first paragraph. One could not understand what they were saying. In this section, the researchers were supposed to state how the validation exercise was done. That was not done. In paragraph two, they indicated that every average age was 1.18. how possible is that? 2.5 Data Collection Procedures\n\nOn the assumption that the researchers set out to develop and validate an instrument, one had expected to see in this section, how items were generated, how many they were and what they did with those items. These things were not seen. For one to assess this section, there is, therefore, need to know the general purpose of the study. As it to validate an existing instrument or to develop and validate an instrument. 2.6 Method of Data Analysis\n\nThe researchers should be specific about which statistical technique that was used to address each issue. The first two paragraphs under Analysis of data and Results should be moved to Method of Data Analysis. This recommended adjustment is clearly necessary when one looks at the contents of the last paragraph under Method of Data Analysis and the first two paragraphs under Analysis and Results. 3.0 Analysis and Results\n\nThe caption of this section should be ‘Results’ instead of ‘Analysis and Results’.\n\nWhere is evidence of this initial – EFA – mentioned in the first paragraph?\n\nSome issues that are worrisome which needs addressing in this section are: If a sample of 550 was used for the EFA, which number was the sample size for the CFA? Was it the same sample that was used for both EFA and CFA? 3.1 Confirmatory Factor Analysis (CFA) and Overall Construct Validity\n\nThe researchers claimed here that there was study one. What was done in that study?\n\nSuddenly in Section 3.0 (Results), readers were being told of an earlier exploratory factor analysis that was done. Nothing in the Introductory section of this research report or the Method Section made the reader to know that there was EFA. This information suddenly appeared under Results Section. That is not acceptable.\n\nIn the opening paragraph of this section (3.1), the researchers were still telling the reader about what was done. All these need to have been exhausted under the Method Section. What are needed in the Result section are simply the results. Mention was made of Table 1 in this Section 3.1 but one cannot see the Table being referred to. After presenting Figure 1, there was no attempt to explain its contents in a text.\n3.2 Testing the Measurement Model\n\nThere appears to be inconsistency in the naming of the MOL factor. In some sections it was named mutilation of library materials, while in some sections (e.g. 3.2) it is named theft and mutilation of library materials. Having drawn the attention of a reader to a table, the next thing should be to describe the table in a text. Where were the contents of Table 2 explained. In writing, we do not talk of table below or above.\n\nThe title of Fig. 2 should simply read: Factor Distributions and Values obtained from the Second-Order CFA model. One had difficulty in understanding Tables 3, 4 and 5.\n4.1 Convergent Validity\n\nThis section should be for result, and what we expect to see are the results. All the information in the first paragraph should have come earlier in the previous sections. Alternatively, any relevant points in the section could be used to support obtained result.\n\nThe researchers made reference to Table 3 in the second paragraph but one could not see the factor loadings in question in that Table. The authors could not effectively connect each of the Tables with their corresponding texts. This applied to most of the Tables. In some cases, some of the information in the text differ from what are in the tables.\n\nSuddenly, below Table 5, the authors were talking of correlation between GPA and sub-scales of PGS. This was not in the picture previously. The report of literature claimed in the first line of this section was not covered in this paper. 5.1 Confirmatory Factor Analysis and Model Fit\n\nThe researchers stated in specific terms in the first paragraph of this section that the present study was aimed at validating an existing instrument. If that is the case, they have to go back to the beginning and present the argument focused on that.\n\nThe first two paragraphs of this section contain information that should have appeared earlier, may be under Method of Data Analysis. The third paragraph was simply a re-presentation of the information in the result section. One cannot see where the results were discussed. The same thing applied to the succeeding paragraphs.\n\nRegarding the results, the researchers appeared not to have communicated very well in the section for result presentation. One thing is to get good result, the other thing is to report it in an understandable manner. 6.0 Conclusion and Practical Implications\n\nThe contents were more of re-presentation of results than conclusion.\nAPPROVAL STATUS OF THE ARTICLE\n\n-------- Not Approved\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": "332208",
"date": "12 Nov 2024",
"name": "Ilavenil Karunakaran",
"expertise": [
"Reviewer Expertise Medical education",
"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 propensity to indulge in academic cheating threatens academic integrity and it is commendable that authors have taken up an inquiry into this topic of research.\n\nThe manuscript in its present form will benefit from major revision and rescripting in the following areas:\nPresentation: There is lack of logical flow to the research report and there is unacceptable repetition and unorganized content.\nThe Introduction must include references specific to the development of the scale, CGPA and academic self-concept and edit out detailed introduction on prevalence. This will set the tone for the research objectives and research questions. The Introduction does not talk about Self-concept that has been part of the study. It suddenly appears later (in 2.1 research design ) Research questions Check grammar of \" Analyze the PCS’s convergent and discriminant validity in particular.\" Methods There are repetitive iterations of why a particular method was used. They detract from communicating the exact methods that were used and when they were used. The methodology could include a workflow chart that will show the timeline process of the research and the sample sizes involved. It is unclear until one reads the Conclusions and practical implications that the PCS was developed as a part of the study. This is in contrast a statement (under Problem statement para 4) which mentions that \" no prior research... … validity of the PCS employed by these institutions\", which suggests that a PCS was already in place locally. The numbering of subsection 2.4.1 is not justified since there is no 2.4.2. The mean age of participants (mentioned wrongly as 1.18) should be reported in the results under participant characteristics. Analysis and results the first two paragraphs should be part of the methodology. Much of the Analysis and Results sections contains methodology and discussion. This makes the reader sift through the text to read the results and this interrupts the logical flow of the report. Adding appropriate legends and labels to the figures 1 & 2 will make them self-explanatory Discriminant validity …. there is no result reported regarding the research question 2 \"To what extent do the items in the instrument of PCS show discriminant validity?\" . The results reported have evaluated subscales or dimensions (as has been mentioned) of PTC and not the 'items'. Abbreviation errors: Cumulative Grade Point Average is mentioned first in the introduction but the abbreviation is given in the last section of Results and Analysis (4.2 Discriminant validity). EFA appears early (on first paragraph of 3.methods) but the abbreviation is mentioned only later (in the first paragraph 3.3 testing the structural model). Conclusion: It is only a summary of the results and discussion and includes references to validate the interpretation of the results.\n\nThe above are only a few illustrative examples of why the manuscript has to be redrafted for clarity. Manuscripts needs to be checked for grammatical errors.\n\nStudy design: The framing of the research questions and the particular sequence of research methods used to investigate them are obscured by explanations of why they are done rather than reporting what was done and in what sequence.\n\nDetails of methods and analysis:\n\nThe first paragraph of Methods mentions the 'findings from the EFA study'. This is unclear and has to be rephrased for clarity. 3.1 Confirmatory factor analysis and overall construct validity : What is Study 1 which has been mentioned ? There has been no reference for the same. There are a lot of missing explanations in the methods regarding details of how the PCS was developed, what were the types of items, was the self-concept scale administered, how was it scored, what was the CGPA recorded, details of EFA and CFA samples and any revision of scale. While the article talks about the multidimensionality of cheating, the authors have not addressed the other factors that will vouch for the comprehensiveness of the scale. This is why the derivation of the scales, subscales and items has to be described in detail. Were items on the scale limited to any specific timeframe? What are the questions that will allow for triangulation, considering that students might not be honest in answering items on a 'propensity to cheat' scale ? This is a major snag in using the scale and it will be interesting to note author's viewpoints regarding this factor in the study design.\n\nInterpretation and Conclusion:\n\nThe entire report does not provide a readily obvious answer to the two research questions that have been raised. The mentioned research questions do not sufficiently reflect all aspects of the primary objective. The statement that ' In conclusion, this study has established the multidimensional character of the concept of PTC' is unacceptable. This was not the objective nor was was it warranted by study methods.\n\nThe relation of CGPA and concept of self to PTC is also not clear. The conclusion must place the findings of the study in the context of the research area of interest and describe the impact of the findings.\n\nSUMMARY OF REVIEW: Authors must first re-evaluate what they have done and ensure that they edit out unnecessary text and include the needed details to produce a coherent research report. At present, it is unclear what the researchers intended to do, what they did, and what can be interpreted from the results.\n\nFinally, I am curious to know the ethical considerations of administering a Propensity To Cheat scale to students of higher education. Despite validation, the response bias will always counteract true estimation of the constructs and thereby turn out to be self-defeating. Authors must address this query to establish relevance.\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? 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? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "13240",
"date": "30 Jan 2025",
"name": "Dame Taye",
"role": "Author Response",
"response": "Authors’ Response to Reviewer’s Questions or comments or suggestions on “Confirmatory Factor Analysis and Students' Propensity to Cheat Scale Validation in the Ethiopian Public Higher Education Institutions” Title: Confirmatory Factor Analysis and Students' Propensity to Cheat Scale Validation in Ethiopian Public Higher Education Institutions Response to Reviewer’s 2 Comments: Presentation Authors Response: Thank you for your feedback. We reorganized the content to improve logical flow and coherence, eliminate any repetitive information to update the manuscript and ensure that each section transitions smoothly to the next. Introduction Authors' Response: We appreciated your feedback and revised the Introduction accordingly. We included references specific to CGPA, and academic self-concept. Additionally, we introduced the concept of self-concept earlier in the Introduction to maintain consistency. Research Questions Authors Response: Thank you for bringing this to our attention. We revised the sentence to state, \"In particular, analyze the convergent and discriminant validity of the PCS.\" Methods Authors' Response: The Methods section was updated to eliminate repetitive explanations and to focus on the specific methods used and their sequence. A workflow chart was included to illustrate the timeline process and sample sizes. It was clarified that the PCS was validated as part of this study, and the numbering of subsections was corrected. Additionally, the mean age of participants was accurately edited in the Results section under participant characteristics. . Analysis and Results Authors' Response: The first two paragraphs of the Analysis and Results sections were moved to the Methodology section to enhance clarity. This adjustment ensured that the Analysis and Results sections focused solely on presenting the findings. Additionally, appropriate legends and labels were added to Figures 1 and 2 to make them self-explanatory. Discriminant validity Authors' Response: The results included a specific examination of the discriminant validity of the items in the PCS instrument, which ensured that the research question was fully addressed. Discriminant validity assesses the extent to which a test does not correlate with other tests that measure different constructs. In this context, the weak correlation observed between the PTC and academic self-concept (ASC) suggested that the PTC scale measures a distinct construct, thereby supporting its discriminant validity. To evaluate this validity, the distinctiveness of the PCS items was examined about unrelated constructs. The findings revealed low correlations between the PCS items and these unrelated constructs, further confirming their discriminant validity. Abbreviation errors: Authors Response: \"We ensured that all abbreviations were introduced at their first mention in the manuscript to maintain consistency and clarity.\" Conclusion Authors' Response: The Conclusion was revised to provide a more comprehensive discussion of the findings and their implications. Additionally, the manuscript was thoroughly checked for grammatical errors. Study design: Authors Response: The Study Design section was revised to report the sequence of research methods used, emphasizing what was done rather than why it was done. Details of methods and analysis: Authors Response: Thank you very much! In the revised version of the Methods section, we rephrased the first paragraph for clarity. We provided a reference for Study 1 and included explanations regarding the development of the PCS, the types of items included in the academic self-concept scale, and CGPA. Additionally, we incorporated the samples used for both Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). Furthermore, we addressed the comprehensiveness of the scale and discussed the potential for response bias within the study design. Interpretation and Conclusion: Authors Response: Thank you very much! We revised the manuscript to ensure that the research questions were answered and reflected all aspects of the primary objective. We rephrased the conclusion to accurately represent the study's objectives and methods. Additionally, we clarified the relationship between CGPA, self-concept, and PTC, and discussed the impact of the findings within the context of the research area. Summary of Review: Authors Response: Thank you very much! We re-evaluated the manuscript to remove unnecessary text and included the essential details to ensure a coherent manuscript. Additionally, we addressed the ethical considerations related to administering the PCS to students and discussed the potential impact of response bias on the study's findings."
}
]
}
] | 1
|
https://f1000research.com/articles/13-955
|
https://f1000research.com/articles/13-954/v1
|
23 Aug 24
|
{
"type": "Opinion Article",
"title": "Perspectives and guidance for developing artificial intelligence-based applications for healthcare using medical images",
"authors": [
"Bapu Koundinya Desiraju",
"Ramachandran Thiruvengadam",
"Nitya Wadhwa",
"Ashok Khurana",
"Aris T Papageorghiou",
"J. Alison Noble",
"Shinjini Bhatnagar",
"Bapu Koundinya Desiraju",
"Ramachandran Thiruvengadam",
"Nitya Wadhwa",
"Ashok Khurana",
"Aris T Papageorghiou"
],
"abstract": "Artificial intelligence (AI) has significant potential to transform healthcare and improve patient care. However, successful development and integration of AI models requires careful consideration of study designs and sample size calculations for development and validation of models, publishing standards, prototype development for translation and collaboration with stakeholders. As the field is relatively new and rapidly evolving there is a lack of guidance and agreement on best practices for most of these steps. We engaged stakeholders in the form of clinicians, researchers from academia and industry, and data scientists to discuss various aspects of the translational pipeline and identified the challenges researchers in the field face and potential solutions to them. In this viewpoint, we present the summary of our discussions as a brief guide on the process of developing AI-based applications for healthcare using medical images. We organized the entire process into six major themes (i.e., The gaps AI can fill in healthcare, Development of AI models for healthcare: practical and important things to consider, Good practices for validation of AI models for healthcare: study designs and sample size calculation, Points to consider when publishing AI models, Translation towards products, Challenges and potential solutions from a technical perspective) and presented important points as a rule of thumb. We conclude that successful integration of AI in healthcare requires a collaborative approach, rigorous validation, adherence to best practices as described and cited, and consideration of technical aspects.",
"keywords": [
"Medical imaging",
"Artificial intelligence",
"AI in healthcare",
"Guide",
"Introduction",
"Rules of thumb"
],
"content": "Introduction\n\nArtificial intelligence (AI) in healthcare is an interdisciplinary field that requires expertise across several disciplines including clinical medicine, engineering, computer science, and statistics.1,2 As this field evolves, workshops and discussions can serve an important purpose to educate early career researchers and all those new to AI. We, an interdisciplinary and international research collaborative team (The University of Oxford, UK and the Translational Health Science and Technology Institute (THSTI), India) organized three workshops on AI in healthcare attended by clinicians, physician-scientists, biologists, computer vision scientists, engineering and medical students. We summarize here the key messages from the thought-provoking discussions held in the six apriori identified themes of the three workshops (Figure 1). We hope that this article serves both as an introductory guide and as a compendium of rules of thumb checklist for researchers (publicly available on our YouTube channel).\n\nThe first workshop focused on introducing this interdisciplinary field to the participants, with discussions on specific use cases of AI in clinical practice. This was followed by the identification of problem areas (research questions) in maternal and child health where AI may be used to find sustainable solutions. In the second workshop, we discussed in detail the process of development, validation, and reporting strategies for AI models. In the third and final workshop, we discussed challenges of integrating AI-enabled solutions into public health, and potential solutions and strategies for addressing bias in data, generalizability, and data sharing. We also explored the difficult task of collecting and managing multidimensional clinical data and how to address the associated challenges.\n\n\nSummary of the discussions\n\nDifferent classes of AI models support different types of healthcare tasks. Understanding the use case is key and can influence the study designs of development and validation. This ensures that appropriate evidence is generated to enable clinical application.\n\n• Assistive models help physicians automate non-trivial but repetitive tasks. One important example is of models which can automatically identify anatomy of interest in an ultrasound scan and measure relevant parameters such as fetal biometry.3,4 These models might reduce the time taken and enable consistency of quality for healthcare practitioners to complete their tasks.\n\n• Diagnostic models are intended to automatically diagnose a disease. Some examples are models that screen large numbers of chest X-rays for tuberculosis5 or retinal images for diabetic retinopathy.6 These facilitate preliminary risk stratification (screen) before a medical expert confirms the diagnosis.\n\n• Prognostic models are designed to predict a patient’s prognosis, e.g cancer recurrence,7 5-year survival, etc. It is prudent to note that unlike the previous two examples, these types of models predict future events and therefore a physician cannot identify and correct a model’s mistake.\n\nAt the outset of the research process, there is an element of context - the research question. We strongly recommend thinking about a few questions like “What are we endeavoring to predict?”, “How important is the problem at the level of application?” and “How would clinicians use the tool in their workflow?”. We opine that there should be a level of engagement from the beginning, right at the point of study design, with all stakeholders. This includes regulators, clinicians, patients, and the investigators who will conduct the study.\n\nFrom the outset, we recommend planning for validation and appropriate metrics for evaluating the model. A few relevant examples would be discussions about ground truth, study design for validation and appropriate metrics (for example sensitivity or specificity) and to optimize for a given clinical context. There are some specific challenges in finding the benchmarks against which these AI models can be compared. The most intuitive way is to compare against a panel of clinical experts. However, it is advisable to keep some caveats in mind, while considering this mode of comparison. When clinicians make a diagnosis, they have more contextual or corroborating information about patients, such as their symptoms, investigations, and clinical history. In contrast, AI models are typically provided with information limited to images and therefore a direct comparison of models with clinicians maybe not appropriate. It is recommended that such contextual information is incorporated while developing the AI models. Quality assurance of the input data, manual annotations (ground truth) and the deidentification process are other pertinent factors. Questions like “How do you measure intra- and inter-annotator agreement?”, “What should be considered the gold standard?”, “How much error is tolerable?” must be discussed while designing the study. In addition, we suggest that both automated data collection pipelines and quality assurance checks should be in place before data collection starts. Automation in both quality assurance and annotation is essential as investigators cannot manually check all the data points, for large-scale studies involving several thousands of images or videos. All these considerations clearly emphasize the importance of an interdisciplinary team and constant engagement from the start with all multidisciplinary stakeholders.\n\nIt is well-known that the models perform optimistically when evaluated or tested in the population in which they were developed. The demand for external validation along with development studies has increased from the scientific community. A recent review of studies that developed AI models for diagnostic analysis of medical images found that only 6% of 516 studies had conducted external validation.8 Another study reported that there were a relatively small number of prospective studies on medical imaging. Randomized clinical trials conducted in the past have been found to be at high risk of bias and deviating from existing reporting standards.9,10 Hence, it is essential to carefully consider validation methods and appropriate practices to follow for external validation studies of AI models. In the literature there is sometimes confusion between internal and external validations. During internal validation, the model is evaluated for accuracy and robustness. In contrast, external validation measures the model’s generalizability and clinical effectiveness. We reiterate that testing the model on data collected along with the training data but kept separate from the training process is not external validation. True external validation is when the model is tested on data collected at a site (or setting) completely different from the site (or setting) at which data is collected and used for the development of the model. External validation should have a different setting, population, geographical location, or time and should depend on the context in which the model is meant to be used. Ideally, external validation would be conducted with data from more than one setting.\n\nFor models that predict a future outcome or event, the ideal study design for validation of AI models would be a cohort study. A cross-sectional study will be appropriate if the model is intended to diagnose a disease. We suggest that interventional study, like a randomized controlled trial should be considered only when clinical effectiveness of a model is being evaluated. Validation on retrospective data is simpler and quicker but needs to be done keeping in mind that investigators may not have had control over how the data was collected; these validations would have a high risk of bias. The aim of prediction model development studies is to estimate the coefficients robustly, but in external validation studies the focus shifts to estimation of model performance. Since the two steps focus on two different but important aspects, validation studies should not be an afterthought. Critical to good validation study design is sample size estimation. We recommend investigators to follow recently developed guidelines and best practices for sample size estimation for prediction model validation.11,12\n\nWhile discrimination is the ability of the model to distinguish between the groups, calibration, on the other hand, measures the alignment between predicted probabilities and the actual frequency of events, ensuring that the model’s confidence scores are reliable. The model performance should be measured in terms of discrimination, calibration, and clinical utility on external validation data sets. Discrimination should be measured area under the curve of receiver operating curve (AUROC) for classification models, Calibration slope and intercept should be reported to assess model bias. Finally, to assess clinical utility, a decision curve analysis is recommended.13\n\nThis theme identifies key considerations while writing a manuscript for peer review and publication. A recent systematic review of the diagnostic accuracy of deep learning and medical imaging found that there is high heterogeneity between studies. This is due to varying methods, terminology, and outcome measures, indicating a need for developing reporting and methodological guidelines for significant issues in this field. Reporting guidelines are not new in the field of medical and epidemiological research (EQUATOR network) The domain of AI in medical imaging is multidisciplinary and mandates that reporting should be in a way that is easily comprehensible by the end users of these models. While a broad consensus towards such reporting is evolving, there are existing publishing guidelines and checklists such as the CLAIM14 and TRIPOD.15 The publication of the model is an important intermediary step between the development and validation of the model. Authors should consider sharing all essential information required for reproducibility and transparent implementation of the model by other researchers. Reproducibility is greatly facilitated by releasing the model and implementation code. We recognize that this is not always possible in healthcare AI, especially for stakeholders in industry and where data governance restrictions forbid release of data used to build a model. In such situations, wherever possible, release of a web-based implementation of a model, which would keep intellectual property secure would be important. We also recognize that grand challenges, open competitions with data and code, play an important role in model benchmarking. Although they typically capture only real-world scenarios in a limited way they can encourage “data engineering gaming” to incrementally beat prior work. Overall, researchers need to take the responsibility to report their work in a scientifically rigorous way with clear descriptions of the data set, eligibility criteria, the context in which the model is to be used, appropriate metrics, and an implementation plan to facilitate the next steps in the translation pipeline. Peer review needs to become more rigorous to ensure that AI model reporting standards are elevated.\n\nThe final step in translating any AI model is to produce a prototype that can be used by healthcare workers. Academic publication plays a crucial role in technology translation and how authors present the information is of paramount importance. Authors should maintain a balance between sharing information and retaining the details that help commercialization of their technology. We emphasize that authors should define the technology performance level clearly and report limitations so that the end-user can utilize it effectively. A major obstacle to adoption of AI is because benefits of AI are not clear to clinicians.16 It would be advisable that instead of simply handing the stakeholders any new AI-based technology, they should be trained on use of model in real life situations which will also allow them to appreciate the improvement the technology brings to their daily workflow. There is an urgent need for low-cost (or zero extra cost) AI solutions requiring minimal clinical expertise for healthcare workers. In summary we recommend four stages that any AI prototype should undergo before being accepted for clinical use: peer-reviewed publication of the model, external validation, regulatory approval, and recommendation by professional societies. A clear plan of the deployment scenario while developing the product will facilitate translation.\n\nTo date, the black-box nature of current AI models has led to slow adoption of this technology in medicine where the cost of a mistake is high. Explainable artificial intelligence (also called interpretable AI) has been suggested to generate trust among the health-care professionals, to bring transparency into AI decision-making, and mitigate biases. Currently, there are several methods to test the explainability of AI models. A heat map (also known as a saliency map) is a popular method that uses activations of convolutional layers to demonstrate the extent to which each region of the image contributed to the model’s decision. They are illustrative and are easy to understand but do not always correspond to human intuition for important in decision-making. Class activation maps (CAM)17 and its extension Grad-CAM18 are among the popular methods that are used to generate these explanations. Besides heat maps, locally interpretable model-agnostic explanations (LIME)19 and Shapley values (SHAP)20 seek to understand decisions at the individual level by altering the input example and identifying the alterations that contributed to the decision. In the case of image analysis, this is done by occluding parts of the image. While the above approaches aid in understanding the clinical perspective, other approaches such as feature visualization are used by machine learning engineers. Feature visualization involves producing synthetic inputs that activate specific parts of a machine learning model strongly. Each model decision can then be described as a combination of a series of features that were detected in the input. Nevertheless, all these methods are just approximations and do not include explanations in terms of medical findings. This in turn makes the interpretation of AI models rather subjective. This area of research is still in its nascent stage and more work is needed to develop truly explainable AI.21 In the absence of suitable explainability methods, we advocate for rigorous internal and external validation of AI models as a more direct means of achieving the goals.\n\nThe ability of the model to give accurate predictions on an external data set collected separately from the training data set is called generalizability. Despite a large amount of published work on AI applications in medicine, only a relatively small number of these models are implemented in clinical practice primarily due to the lack of generalizability of models, though this number is also growing.22,23 Site to site customization in image acquisition, different standards of implementation in clinical practice, differences in patient demographics across centers, genotypic and phenotypic characteristics of patients, and tools and methods used to process and develop medical data are just some of the factors that may affect generalizability. Another significant factor that affects generalizability is training the model on biased data. Some of these factors can be adjusted using recent methodological advances such as domain adaptation techniques. In domain adaptation, the goal is to adapt models to target data sets based on labeled samples from the source environment as well as a limited set of unlabeled samples from the target environment.\n\nProbably the best solution is to collect training data from different centers and incorporate all the real-world variations in it. However, collecting a huge medical data set from multiple sites is time-consuming, expensive, and poses data sharing challenges. Federated learning,24 an emerging methodological advancement, may aid researchers in overcoming the data sharing challenge. This framework helps researchers to train AI models while retaining data at individual sites. To summarize, different models of the same architecture are trained separately at each site using data from the site, and then these partial models are combined to create a global model.\n\n\nConclusion\n\nIn this article, we present the discussions held during the three workshops as useful take home messages. The shared insights offer a foundational guide for researchers aiming to embark on their journey in this rapidly advancing and transformative field. In summary, to ensure successful integration of AI models in clinical practice, researchers must engage with all stakeholders, including clinicians, regulators, and patients, from the outset and use robust study designs for validation ‘The crucial steps are validating AI models in external data sets using adequate sample sizes for estimation of robust performance metrics. While publishing these models, transparency, reproducibility, and following reporting guidelines are strongly emphasized. Clinician training on AI technologies is vital for their understanding of the benefits these models bring in their clinical workflows for effective adoption. From a technical standpoint, explainability and generalizability are major challenges. Overcoming variations in data collection and ensuring models’ applicability across different settings are essential for generalizability.\n\n\nContributions\n\nBKD, RT, NW, AK, AP, AN & SB have designed and coceptualised the scientific content of the workshops. BKD, RT, AN & SB have written the viewpoint.\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\nAcknowledgments\n\nWe thank all speakers and participants of our workshops for their valuable inputs.\n\n\nReferences\n\nHaug CJ, Drazen JM: Artificial Intelligence and Machine Learning in Clinical Medicine, 2023. N. Engl. J. Med. 2023; 388(13): 1201–1208. Publisher Full Text\n\nRajpurkar P, Lungren MP: The Current and Future State of AI Interpretation of Medical Images. N. Engl. J. Med. 2023; 388(21): 1981–1990. PubMed Abstract | Publisher Full Text\n\nChen H, Wu L, Dou Q, et al.: Ultrasound Standard Plane Detection Using a Composite Neural Network Framework. IEEE Trans Cybern. 2017; 47(6): 1576–1586. PubMed Abstract | Publisher Full Text\n\nSharma H, Droste R, Chatelain P, et al.: Spatio-Temporal Partitioning and Description of Full-Length Routine Fetal Anomaly Ultrasound Scans. Proc IEEE Int Symp Biomed Imaging. 2019; 16: 987–990. PubMed Abstract | Publisher Full Text\n\nQin ZZ, Ahmed S, Sarker MS, et al.: Tuberculosis detection from chest x-rays for triaging in a high tuberculosis-burden setting: an evaluation of five artificial intelligence algorithms. Lancet Digit Health. 2021; 3(9): e543–e554. PubMed Abstract | Publisher Full Text\n\nAbramoff MD, Folk JC, Han DP, et al.: Automated analysis of retinal images for detection of referable diabetic retinopathy. JAMA Ophthalmol. 2013; 131(3): 351–357. PubMed Abstract | Publisher Full Text\n\nKim JY, Lee YS, Yu J, et al.: Deep Learning-Based Prediction Model for Breast Cancer Recurrence Using Adjuvant Breast Cancer Cohort in Tertiary Cancer Center Registry. Front. Oncol. 2021; 11: 596364. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKim DW, Jang HY, Kim KW, et al.: Design Characteristics of Studies Reporting the Performance of Artificial Intelligence Algorithms for Diagnostic Analysis of Medical Images: Results from Recently Published Papers. Korean J. Radiol. 2019; 20(3): 405–410. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNagendran M, Chen Y, Lovejoy CA, et al.: Artificial intelligence versus clinicians: systematic review of design, reporting standards, and claims of deep learning studies. BMJ. 2020; 368: m689. Publisher Full Text\n\nO’Shea RJ, Sharkey AR, Cook GJR, et al.: Systematic review of research design and reporting of imaging studies applying convolutional neural networks for radiological cancer diagnosis. Eur. Radiol. 2021; 31(10): 7969–7983. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSnell KIE, Archer L, Ensor J, et al.: External validation of clinical prediction models: simulation-based sample size calculations were more reliable than rules-of-thumb. J. Clin. Epidemiol. 2021; 135: 79–89. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCollins GS, Ogundimu EO, Altman DG: Sample size considerations for the external validation of a multivariable prognostic model: a resampling study. Stat. Med. 2016; 35(2): 214–226. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSteyerberg EW, Vergouwe Y: Towards better clinical prediction models: seven steps for development and an ABCD for validation. Eur. Heart J. 2014; 35(29): 1925–1931. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMongan J, Moy L, Kahn CE Jr: Checklist for Artificial Intelligence in Medical Imaging (CLAIM): A Guide for Authors and Reviewers. Radiol Artif Intell. 2020; 2(2): e200029. Publisher Full Text\n\nCorrection: transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. Ann. Intern. Med. 2015; 162(8): 600. PubMed Abstract | Publisher Full Text\n\nKhairat S, Marc D, Crosby W, et al.: Reasons For Physicians Not Adopting Clinical Decision Support Systems: Critical Analysis. JMIR Med. Inform. 2018; 6(2): e24. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhou B, Khosla A, Lapedriza A, et al.: Learning Deep Features for Discriminative Localization.2015 December 01, 2015. [arXiv:1512.04150 p.]. Reference Source\n\nSelvaraju RR, Cogswell M, Das A, et al.: Grad-CAM: Visual Explanations from Deep Networks via Gradient-based Localization.2016 October 01, 2016. [arXiv:1610.02391 p.]. Reference Source\n\nTulio Ribeiro M, Singh S, Guestrin C: \"Why Should I Trust You?\": Explaining the Predictions of Any Classifier.2016 February 01, 2016. [arXiv:1602.04938 p.]. Reference Source\n\nRozemberczki B, Watson L, Bayer P, et al.: The Shapley Value in Machine Learning.2022 February 01, 2022. [arXiv:2202.05594 p.]. Reference Source\n\nSadeghi Z, Alizadehsani R, Akif Cifci M, et al.: A Brief Review of Explainable Artificial Intelligence in Healthcare.2023 April 01, 2023. [arXiv:2304.01543 p.]. Reference Source\n\nYang J, Soltan AAS, Clifton DA: Machine learning generalizability across healthcare settings: insights from multi-site COVID-19 screening. NPJ Digit Med. 2022; 5(1): 69. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEche T, Schwartz LH, Mokrane FZ, et al.: Toward Generalizability in the Deployment of Artificial Intelligence in Radiology: Role of Computation Stress Testing to Overcome Underspecification. Radiol Artif Intell. 2021; 3(6): e210097. Publisher Full Text\n\nRieke N, Hancox J, Li W, et al.: The future of digital health with federated learning. NPJ Digit Med. 2020; 3: 119. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "320762",
"date": "10 Sep 2024",
"name": "Piotr Szczypinski",
"expertise": [
"Reviewer Expertise Image and signal processing",
"medical and agrophysics applications",
"algorithms and software 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\nThe language of the article is confusing, unclear and imprecise. The text uses buzzwords without explaining their meanings. Lack of in-depth presentation of the problems. Lack of discussion and critical approach to the presented problems. The text of the article seems to treat the topic superficially without a deeper analysis of the problem. The text is not didactic in nature because it does not clearly explain the presented problems and their causes. The text is also not scientific in nature because it does not present substantive argumentation, problem analysis, discussion and critical evaluation. The text presents the opinions of the authors or a larger group of people participating in three unspecified workshops, but its form and content are more like a blog or organized notes from a meeting, rather than an article meeting the requirements of a scientific report. I therefore estimate that the group of recipients of this text will be relatively narrow. According to the authors, the text is to be a guide to the transformation of medical services using AI. However, in my opinion it does not meet this condition either. The presented opinions and recommendations do not have a deeper justification and explanation. It is difficult to agree with some of the opinions, they are formulated in a general way and in such a context they become untrue. They may be true in relation to specific cases, but this is not clear from the text. The authors' recommendations are therefore questionable because they are not preceded by a substantive analysis of the problem, discussion and critical assessment. The text does not present a comparison of different artificial intelligence technologies. Expert systems, feature engineering methods or deep machine learning have completely different meanings and applications in medicine. These technologies are so different that they cannot be lumped together. Their use in medical applications gives rise to completely different problems and doubts. Therefore, the text in its current form is not ready for indexing as a full-fledged scientific paper. By presenting opinions unsupported by justification, it has the character of a blog or maybe a popular science report. It should be noted, however, that the text lists and tries to organize issues related to the application of AI in medicine. As such, it can be an introduction to a larger study in this topic. I hope that the authors will prepare such a reliable study.\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? No\n\nAre arguments sufficiently supported by evidence from the published literature? No\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
},
{
"id": "339980",
"date": "31 Dec 2024",
"name": "Michał Strzelecki",
"expertise": [
"Reviewer Expertise medical imaging",
"image analysis",
"AI applications"
],
"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 reviewed paper fits into the works discussing the direction of development of artificial intelligence in medicine, where its presence is becoming increasingly noticeable. The work was created as a summary of the discussion held during several workshops organized by the authors of this publication with representatives of various environments potentially interested in implementing AI in clinical practice. It should be noted here that the paths for validating such models are already well-developed and used in practice. See e.g. the Federal Drug Administration, which has already approved over 1,000 AI algorithms to support diagnostics in various medical specialties. The principles for publishing scientific papers, which are generally correct, are also presented. Please remember, however, that companies that develop AI for medical applications are interested in making money, so they will not share their knowledge or describe the details of the solutions developed. It is a pity that the work did not address important issues, such as the need to educate patients and doctors about the implemented AI solutions used or the legal and ethical problems related to the need for access to multimodal and multi-center medical data. To sum up, the paper lacks a fresh and inspiring perspective on the implementation of AI in medicine. Therefore, the scientific and didactic value of this work is very limited.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? No\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? No\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-954
|
https://f1000research.com/articles/13-953/v1
|
23 Aug 24
|
{
"type": "Clinical Practice Article",
"title": "Case Report: A right-sided testicular artery of renal origin, in coexistence with a renal artery duplication: Dissection findings with clinical significance",
"authors": [
"Natsis Konstantinos",
"Ediaroglou Vasilios",
"Totlis Trifon",
"Tsakotos George",
"Triantafyllou George",
"Petrou Vasileios",
"Piagkou Maria",
"Natsis Konstantinos",
"Ediaroglou Vasilios",
"Totlis Trifon",
"Tsakotos George",
"Triantafyllou George",
"Petrou Vasileios"
],
"abstract": "Purpose The current cadaveric report describes the abnormal origin and course of testicular arteries (TAs) in two donated cadavers, along with a renal artery (RA) duplication.\n\nMethods Dissection of the inferior vena cava (IVC) and the abdominal aorta (AA) branching patterns were performed in 90-year-old- and 76-year-old formalin-embalmed donated male cadavers.\n\nResults Variants of the TA origin and course were identified, as coexisting with RA variants.\nCase 1:\nA right-sided RA (RRA) duplication (recorded as superior and inferior renal artery-SRA and IRA) with origin from the AA, coexisted with a right TA (RTA) that originated from the IRA and descended anteriorly to the ureter. The left TA (LTA) originated from the AA proximal to the origin of the left RA (LRA). The LTA coursed in front of the common drainage of the left testicular and renal vein into the IVC.\nCase 2:\nA bilateral RA duplication was identified and recorded as SRA and IRA. The right-sided SRA originated from the AA upper level and played the role of the accessory RA (ARA). The main perfusion of the right kidney was performed by the IRA which was further trifurcated into a superior polar, an inferior polar (IPA), and a TA. The RTA had a high origin from the IPA.\n\nConclusion The current study reported two cases of TAs with abnormal origin and course accompanied by an RA duplication. A thorough knowledge of the origin and course of the TAs has clinical implications for the kidneys and testicle’ surgery.",
"keywords": [
"testicular artery",
"variation",
"renal artery",
"origin",
"duplication"
],
"content": "Introduction\n\nTypical and variant anatomy of the testicular arteries (TAs) or internal spermatic arteries should be carefully studied respectively to their laterality (side of appearance), because of their clinical role in testicular physiology and kidney and testicle surgery. Typically, the long and thin TA originates from the abdominal aorta (AA) anterolateral surface, at a distance of 2.5 to 5 cm distally to the renal artery (RA) origin, and above the inferior mesenteric artery origin.1 The TA supplies the perirenal fat, ureter, iliac lymph nodes, and the cremaster muscle.1–3 It is directed with the testicular vein (TV), retroperitoneal, on the psoas major muscle, enters the inguinal canal through the deep ring, and supplies the testicle.4 The right TA (RTA) originates anterior to the inferior vena cava (IVC) and lies posterior to the duodenum horizontal part, right colic and ileocolic arteries, root of the mesentery, and terminal ileum.1,2 The left TA (LTA) courses posterior to the inferior mesenteric vein, left colic artery, and descending colon.1,2 The right and left testicular veins (RTV and LTV) typically drain into the IVC, and the left renal vein (LRV), respectively.5\n\nTA variants are not rare, as cadaveric studies have shown a prevalence ranging from 4.7% to 8.8%.5,6 The TAs may exhibit an arched course ranging from 1.7% to 20.3%.1 TA variants may be accompanied by TV alterations and the awareness of these venous anomalies may help surgeons accurately ligate abnormal venous anastomosis and avoid iatrogenic injury. TA variants may also coexist with RA alterations. Concerning the RAs, typically, a single RA emanates from the AA, on both sides.7 Frequent variants include the RA variant number7 among different ethnicities (4% in Malaysians, and 61.5% in Indians).8 The presence of multiple RAs is a well-documented phenomenon with a reported frequency of around 20%.7,8\n\nThe present cadaveric report explicitly describes the atypical origin and course of TAs along with an RA duplication and further discusses their clinical implications.\n\n\nCases report\n\nDuring a routine dissection of the IVC and AA branching patterns in two formalin-embalmed donated male cadavers 90-year- and 76-year-old, several variants of the TAs origin and course were identified, as coexisting with RA variants. The cadavers were donated to the Anatomy and Surgical Anatomy Department of the Medical School of the Faculty of Health Sciences of the Aristotle University of Thessaloniki, and the Anatomy Department of the Medical School of the National and Kapodistrian University of Athens, after signed informed consent. The Ethics Committees of the two Universities gave full approval for the study. Case 1: A right-sided RA duplication (RRA) (recorded as superior and inferior renal artery-SRA and IRA) with origin from the AA, coexisted with an RTA that originated from the IRA, and descended anteriorly to the ureter. The LTA typically originated from the AA proximal to the left RA (LRA) origin. The LTA coursed in front of the common drainage of the LTV and LRV to the IVC (Figure 1). Case 2: A bilateral duplication of the RA was identified and recorded as SRA and IRA (Figures 2,3). The right-sided SRA originated from the AA upper level and played the role of the accessory RA (ARA). The main perfusion of the right kidney was performed by the IRA which was further trifurcated into a superior polar artery (SPA), an inferior polar artery (IPA), and a TA. The RTA had an origin from the IPA and descended anterior to the RRV (Figure 2).\n\n\nDiscussion\n\nThe current study describes the TA’s abnormal origin and course in coexistence with an RA duplication.\n\nUnderstanding the developmental stages of arteries provides the basis for understanding morphological variants.5 Regarding the embryological progression of the gonads, which are drained by the mesonephric arteries originating from the AA lateral surface 2,9,10 there are nine pairs1–4,6,11,12 which can be categorized into a cranial group which consists of the 1st and 2nd mesonephric arteries that mature into the celiac trunk, the middle group which consists of the 3rd, 4th, and 5th arteries that develop into the RAs, and a caudal group which consists of the 6th, 7th, 8th, and 9th mesonephric arteries which become the TAs.2 An extra artery in the middle group will typically evolve into the ARA.2,4 If a cranial mesonephric artery does not regress, it will lead to a high-origin TA.1,2,6,12\n\nRegarding the 1st cadaveric report, we hypothesize an additional mesonephric artery in the middle group on the right side led to the RRA duplication. On the left side, there was a persistent cranial lateral mesonephric artery which would explain the LTA’s abnormal origin. The LTA arched course anteriorly to the LRV and the LTV common drainage could be due to the kidney’s position and the higher vertebral level of the LRV compared to the LTA’s origin.1,2,12 This anterior course mimics an unusual variety of nutcracker phenomena.13 The RTAs’ atypical origin of both cadavers can be explained by a possible bifurcation of an additional artery from the middle group of the mesonephric arteries.1,4 One branch would drain the genital ridge and the other would supply the kidney. The TA would come from the former of the two branches.\n\nIn the 2nd cadaver, an extra pair of mesonephric arteries in the middle group would explain the RA bilateral duplication.2,4 On the right side, there was not only one more mesonephric artery that evolved into the ARA but also the other mesonephric artery bifurcation would explain the IRA duplication. TA variants are more common in males than females,2,6,12 and the LTA variants (20.7%) are more common than the RTA variants (12.7%).9\n\nThe TAs typically originate from the AA anterolateral surface, just below the RA origin, at the 2nd or 3rd lumbar vertebrae level (L2 or L3).2,9 The most common variants include alterations in the level, source of origin, number, and course of arteries. TA’s origin can be more proximal than the RA and RV.14 TA’s abnormal origins include the right subcostal artery, the suprarenal artery, the celiac trunk, the right inferior epigastric artery, the superior mesenteric artery (SMA), the inferior mesenteric artery (IMA), the right common iliac, and right external iliac artery.1–3,9,15 TA may originate at the level of the SMA, level of the RA or above,9 in a common trunk with the IMA, and an ARA,15 or in a common trunk with the LTA and RTA from the AA.16 Atypical origins proximal to the L2/L3 level are classified as high-origins, and distal to the L2/L3 or the IMA level are considered low-origins.2,9 The highest origin for the TA was identified at the left side, from the thoracic aorta, proximal to the inferior phrenic artery,10 or above the aortic diaphragmatic hiatus (level of the 12th thoracic vertebra).4 An LTA was identified originating from the LRA in 5.26% and the RTA from the RRA in 2.63%.9 The TA may originate from the main RA, an ARA, or a polar RA.1–4,6,9,15,16 The most common TA variant origins were found in association with renal vessels. Regarding their number, double TA was the most common.1 Concerning the combined TA variants with RA alterations, in the current report, Naito et al.17 recorded the coexistence of multiple RAs (8 in total, arising from the AA) with a bilateral renal origin for the TAs, and Notokovich18 reported gonadal arteries of renal origin in 15%. The number of RAs can be up to six, the most common being 2RAs, similar to the current cadaveric cases. Multiple RAs are reported as the most common renal vascular variant by Satyapal et,19 with an average incidence of 28.2% (range 9-76%). Two or double RAs are reported to make up 89.5% of all multiple RAs.8 Merklin and Michels20 reported incidences for 2RAs, 3RAs, and 4RAs unilaterally of 20%, 2%, and 0%, respectively. Ozkan et al.21 and Sampaio and Passos22 reported an incidence of 0.2% and 0.4% for 4RAs, respectively.\n\nConcerning the TA variant course, the most common variation was an arched course over the ipsilateral RV. Occurrence of the arched TA has been noted on both sides but with a predilection for the left side. An arched RTA had an occasional retrocaval course.1 Kayalvizhi et al.1 concluded an incidence ranging from 1.7% to 20.3% for the arched TA. The arched LTA course over the LRV, similar to the current two unilateral (left and right side) cases is particularly important as it can compress the LRV and impede the venous return from the left kidney and testis. Consequently, varicocele, orthostatic proteinuria, and hematuria can occur. All the observed variants in these two cases could be due to aberrations in the development of visceral vessels controlled by a common molecular regulator.23 Most of these variants are part of the age of the cadaver. Our findings reiterate the old dictum that if an anomaly is detected in one vessel, there are chances of encountering other related anomalies as well. Clinicians need to check for the presence of an arched TA when performing renal surgery, as any injury to this artery might cause testicular atrophy.24\n\nTAs variants although occur frequently, are accidentally discovered intraoperatively.9 The knowledge of the origin and the course of the TAs is clinically important for kidney and testicle surgery and can prevent intraoperative and postoperative complications.1–4,6,7,9,16 Surgeons should consider the RAs’ origin and path when they operate proximal to the renal pelvis or retroperitoneal and particularly target their usage in case of cryptorchism.1,4 The TAs’ abnormal origin and course around the kidney may lead to unexpected serious intraoperative hemorrhage.1,6,9 Radiologists should consider the possibility of variants when performing an angiography with indications, such as recognition of the arterial branches and planning the surgical procedure.1–6,9,15 If any abnormal origin or path of an artery is perceived via angiography, further examinations like magnetic resonance imaging (MRI) and phlebography should be performed to reduce the possibilities of intraoperative and postoperative complications.1 Furthermore, knowledge of the numerous variants of the renal vessels is surgically important in cases of repair renal stenosis, renal infarctions, and renal hypertension, as well as other urological surgeries.1,9,12 Renal arterial hypertension may occur by RA compression and could progress to renal ischemia.1,4,15 The variations could also affect the perfusion and function of testicles.3,4,5 Knowledge of these variations can aid in the prevention of testicular atrophy.1,3,5 These variations could also have serious implications regarding the thermoregulation of the male reproductive tract and consequently have an impact on spermatogenesis.3–5 The lower frequency of the RTA variants compared to the LTA provides an advantage in the usage of the right kidney in transplantations.4 Kidneys with multiple vessels are in high demand for transplantation due to their ability to help more patients who require a transplant.4 Furthermore, a TA originating from the RA may disturb the testicles’ drainage when embolizing renal tumors.2,9,14,25 A case report recorded that during the embolization of a vessel in a renal tumor, an infarction occurred because of an abnormal TA origin from the RA, despite attempts to prevent it.25 Another similar case of testicular infraction has been reported which proceeded from an embolization of a renal angiolipoma.14 Because of the TA arched and anterior course with the RV, there is a potential for RV compression, as seen in the current case description, causing a varicocele secondary to vascular compression.1,2,15 RV compression could also cause venous hypertension, proteinuria, and orthostatic hematuria secondary to the tortuous vascular course.2,15 The TA’s abnormal course could compress the ureter and potentially lead to hydronephrosis.1,4,6\n\n\nConclusion\n\nIn the current cadaveric report, upon performing simultaneous dissections in different locations, similar variants were discovered in the TAs origin and course with RAs duplications in two cadavers. Surgeons should consider the origin and path of the TAs and the possible coexistence of the RAs alterations to prevent intraoperative and postoperative complications.\n\n\nConsent\n\nThe cadavers were donated to the Department of Anatomy and Surgical Anatomy, School of Medicine, Aristotle University of Thessaloneiki and the Anatomy Department of the Medical School of the National and Kapodistrian University of Athens through the Body Donation Program of the universities. The donor signed an informed consent before death giving consent to medical, education and research projects.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgments\n\nThe authors would like to express their gratitude to body donors and their families for their highest contribution to medical education and anatomy research.\n\n\nReferences\n\nKayalvizhi I, Narayan RK, Kumar P: Anatomical variations of testicular artery: a review. Folia Morphol. (Warsz). 2017; 76(4): 541–550. Epub 2017 Apr 10. PubMed Abstract | Publisher Full Text\n\nParaskevas GK, Natsis K, Nitsa Z, et al.: Bilateral double testicular arteries: a case report and review of the literature. Potential embryological and surgical considerations. Folia Morphol (Warsz). 2014; 73(3): 383–388. PubMed Abstract | Publisher Full Text\n\nParaskevas GK, Ioannidis O, Raikos A, et al.: High origin of a testicular artery: a case report and review of the literature. J. Med. Case Rep. 2011; 5: 75. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMamatha H, D’Souza AS, Vinodhini P, et al.: A Cadaveric Study about the Anomalous Origin of Testicular Arteries Arising from the Accessory Renal Arteries. Indian J. Surg. 2015; 77(2): 111–6. Epub 2012 Oct 30. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAsala S, Chaudhary SC, Masumbuko-Kahamba N, et al.: Anatomical variations in the human testicular blood vessels. Ann. Anat. 2001; 183(6): 545–549. PubMed Abstract | Publisher Full Text\n\nCiçekcibaşi AE, Salbacak A, Seker M, et al.: The origin of gonadal arteries in human fetuses: anatomical variations. Ann. Anat. 2002; 184(3): 275–279. PubMed Abstract | Publisher Full Text\n\nCases C, García-Zoghby L, Manzorro P, et al.: Anatomical variations of the renal arteries: Cadaveric and radiologic study, review of the literature, and proposal of a new classification of clinical interest. Ann. Anat. 2017; 211: 61–68. Epub 2017 Feb 3. PubMed Abstract | Publisher Full Text\n\nRecto C, Pilia AM, Campi R, et al.: Renal artery variations: a 20,782 kidneys review. Ital. J. Anat. Embriol. 2019; 124(2): 153–163. Publisher Full Text\n\nNallikuzhy TJ, Rajasekhar SSSN, Malik S, et al.: Variations of the testicular artery and vein: A meta-analysis with proposed classification. Clin. Anat. 2018; 31(6): 854–869. PubMed Abstract | Publisher Full Text\n\nShinohara H, Nakatani T, Fukuo Y, et al.: Case with a high-positioned origin of the testicular artery. Anat. Rec. 1990; 226(2): 264–266. PubMed Abstract | Publisher Full Text\n\nLee HB, Yang J, Maeng YH, et al.: Bilateral multiple renal arteries with an extra-aortic origin and quadruple testicular veins. Anat. Cell Biol. 2019; 52(4): 518–521. Epub 2019 Dec 16. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPai MM, Vadgaonkar R, Rai R, et al.: A cadaveric study of the testicular artery in the South Indian population. Singapore Med. J. 2008; 49(7): 551–555. PubMed Abstract\n\nBraedel HU, Steffens J, Ziegler M, et al.: A possible ontogenic etiology for idiopathic left varicocele. J. Urol. 1994; 151: 62–66. PubMed Abstract | Publisher Full Text\n\nSiniluoto TM, Hellström PA, Päivänsalo MJ, et al.: Testicular infarction following ethanol embolization of a renal neoplasm. Cardiovasc. Intervent. Radiol. 1988; 11(3): 162–164. PubMed Abstract | Publisher Full Text\n\nChakravarthi KK: Unilateral multiple variations of renal, phrenic, suprarenal, inferior mesenteric, and gonadal arteries. J. Nat. Sci. Biol. Med. 2014; 5(1): 173–175. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAdebisi SS, Singh SP: Anomalous gonadal arteries in relation to the renal vein: A preliminary study in nigerians. Niger. J. Surg. Res. 2000; 2: 148–151. Publisher Full Text\n\nNaito M, Hirai S, Terayama H, et al.: Multiple renal vessels associated with testicular vessels. Surg. Radiol. Anat. 2011; 33: 637–639. PubMed Abstract | Publisher Full Text\n\nNotokovich H: Variations of the testicular and ovarian arteries in relation to the renal pedicle. Surg Gynecol Obstet 1956; 103: 487–495.\n\nSatyapal KS, HaVejee AA, Singh B, et al.: Additional renal arteries incidence and morphometry. Surg. Radiol. Anat. 2001; 23: 33–38. PubMed Abstract | Publisher Full Text\n\nMerklin RJ, Michels NA: The variant renal and suprarenal blood supply with data on the inferior phrenic, ureteral, and gonadal arteries: a statistical analysis based on 185 dissections and review of the literature. J. Int. Coll. Surg. 1958; 29: 41–76. PubMed Abstract\n\nOzkan U, Ofuzkurt L, Tercan F, et al.: Renal artery origins and variations: angiographic evaluation of 855 consecutive patients. Diagn. Interv. Radiol. 2006; 12: 183–186. PubMed Abstract\n\nSampaio BJB, Marf P: Renal arteries: anatomic study for surgical and radiological practice. Surg. Radiol. Anat. 1992; 14: 113–117. PubMed Abstract | Publisher Full Text\n\nWadhwa A, Soni S: A study of Gonadal Arteries in 30 adult human cadavers. Clin Med Insights Reprod Heal. 2010; 4: CMRH.S3680–CMRH.S3685. Publisher Full Text\n\nPadur AA, Kumar N: Unique variation of the left testicular artery passing through a vascular hiatus in renal vein. Anat Cell Biol. 2019; 52(1): 105–107. Epub 2019 Mar 29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCummings CT, Foreman R, Killoran TP, et al.: Testicular infarction after angioembolization of an ipsilateral renal angiomyolipoma. Urology. 2013; 82(5): 995–7. Epub 2013 Aug 23. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "316903",
"date": "28 Aug 2024",
"name": "Eren Ogut",
"expertise": [
"Reviewer Expertise anatomical variations",
"alterations",
"types",
"classifications",
"accessory formations",
"morphological variations 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\nAbstract: Abbreviations should be checked from MEDLINE. Case: Surgical background, history, underlying disorders should be added.Conclusion should be written in a more specific and contribution of these cases to the literature should be added and highlighted.Keywords should be written from Mesh on Demand tool. Cases reports: Diameters (horizontal, vertical),thickness and distances should be added. Ethical approval date and protocol ID and Helsinki statement should be added. Figures: Image quality should be increased. Scale bars,directions, arrow head should be added. Discussion : 'Embryological development of the testicular and renal arteries (TAs and RAs)' this parts should be added in introduction part and in the first line, the findings of the article should be presented in a scientific manner, emphasizing their novelty, superiority concerning recent research, and contributions to the existing literature. These parts are the key of the article. Then discuss the recent literature. Missing references and recent articles should be added and discussed in this manner such as: clinical aspects should be discussed from here: [1],[2]. Types and classifications should be added Conclusion: contribution to the literature should be mentioned with novelty.\n\nIs the background of the cases’ 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? No\n\nIs the conclusion balanced and justified on the basis of the findings? Partly",
"responses": []
},
{
"id": "316898",
"date": "29 Aug 2024",
"name": "Savvas Lampridis",
"expertise": [
"Reviewer Expertise surgery",
"translational medicine",
"military medicine",
"health policy"
],
"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 interesting manuscript on testicular artery variations coexisting with renal artery duplications. I appreciate the authors' efforts in documenting these anatomical findings.\nThe manuscript describes two cadaveric cases of abnormal testicular artery origin and course found in conjunction with renal artery duplications. The authors provide anatomical descriptions of the observed variants, along with relevant embryological explanations and a discussion of potential clinical implications.\nStrengths of this work include the clear and detailed anatomical descriptions, inclusion of illustrative figures, and discussion of the embryological basis and clinical relevance of these vascular variants. The authors have also provided a concise but informative literature review to contextualize their findings.\nI have the following comments and suggestions to potentially improve the manuscript:\nThe title could be more specific; perhaps, mentioning that these are cadaveric case reports and specifying the number of cases. In the Abstract, the authors may consider adding a brief statement about the potential clinical significance of their findings. In the Introduction, could the authors consider adding a brief statement about the rarity (or frequency) of finding both testicular artery variants and renal artery duplications simultaneously? This would help readers gauge how unusual these findings are. In the Discussion, the embryological explanation is quite brief. Could this section be expanded to provide a more detailed explanation of how these vascular variants may have arisen? The authors may consider adding a brief paragraph that directly compares the findings in the two reported cases to highlight unique features or similarities. This could help readers better understand the range of the observed variations. Have the authors considered any potential limitations of their study that should be mentioned? For example, how generalizable are findings from elderly male cadavers to the broader population?\nI hope these suggestions are helpful in further strengthening this informative case report. Please let me know if any clarification is needed on my comments.\n\nIs the background of the cases’ 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? Partly\n\nIs the conclusion balanced and justified on the basis of the findings? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-953
|
https://f1000research.com/articles/11-69/v1
|
20 Jan 22
|
{
"type": "Research Article",
"title": "What can we experience and report on a rapidly presented image? Intersubjective measures of specificity of freely reported contents of consciousness",
"authors": [
"Zhang Chuyin",
"Zhao Hui Koh",
"Regan Gallagher",
"Shinji Nishimoto",
"Naotsugu Tsuchiya",
"Zhao Hui Koh",
"Regan Gallagher",
"Shinji Nishimoto"
],
"abstract": "Background: A majority of previous studies appear to support a view that human observers can only perceive coarse information from a natural scene image when it is presented rapidly (<100ms, masked). In these studies, participants were often forced to choose an answer from options that experimenters preselected. These options can underestimate what participants experience and can report on it. The current study aims to introduce a novel methodology to investigate how detailed information participants can report after briefly seeing a natural scene image.\n\nMethods: We used a novel free-report paradigm to examine what people can freely report following a rapidly presented natural scene image (67/133/267ms, masked). N = 670 online participants typed up to five words to report what they saw in the image together with confidence of the respective responses. We developed a novel index, Intersubjective Agreement (IA). IA quantifies how specifically the response words were used to describe the target image, with a high value meaning the word is not often reported for other images. Importantly, IA eliminates the need for experimenters to preselect response options. Results: The words with high IA values are often something detailed (e.g., a small object) in a particular image. With IA, unlike commonly believed, we demonstrated that participants reported highly specific and detailed aspects of the briefly (even at 67ms, masked) shown image. Further, IA is positively correlated with confidence, indicating metacognitive conscious access to the reported aspects of the image. Conclusion: These new findings challenge the dominant view that the content of rapid scene experience is limited to global and coarse gist. Our novel paradigm opens a door to investigate various contents of consciousness with a free-report paradigm.",
"keywords": [
"Consciousness",
"free report",
"rapid scene",
"metacognition",
"confidence",
"gist",
"intersubjective agreement"
],
"content": "Introduction\n\nIntuitively, we have an impression that our visual experience is immensely rich. When we look at a complex natural scene, we can rapidly extract meaningful information and categorize it accurately in as little as 150 ms (Li et al., 2002; Biederman, 1981; Fabre-Thorpe et al., 2001). In certain situations, the performance accuracy is correlated with confidence rating (Fu et al., 2016; Thunell & Thorpe, 2019), indicating some level of metacognitive monitoring is possible. Rapidly extracted information in this context is often called “scene-gist understanding” (Oliva & Torralba, 2006) or “gist” in short. Previous studies demonstrate excellent human capability to rapidly categorise a natural scene based on the scene gist in a global and coarse manner. However, it is unclear whether we have conscious access to more detailed information upon seeing a complex natural image briefly (Bayne & McClelland, 2018; McClelland & Bayne, 2016). The current study will focus on the information beyond “gist”, so that we will use a more general term: rapid scene experience.\n\nIn fact, the current dominant view on contents of rapid scene experience is that it is about high-level descriptions of the scene, which is coarse and lacks the fine details (Campana & Tallon-Baudry, 2013; Fei-Fei et al., 2007; Greene et al., 2015; Kimchi, 1992; Oliva & Torralba, 2006; Greene & Fei-Fei, 2014).\n\nThis dominant view inherits the idea from the Gestalt theory of perception (Koffka, 1922). One of the Gestalt principles states our tendency to perceive a scene as a whole rather than individual parts. This idea was further developed by Navon (1977) in his global precedent hypothesis. This hypothesis posits that visual perception first processes global features of an image, then proceeds to analyze local features. Supplemented by further experimental evidence, Campana and Tallon-Baudry (2013) recently extended this idea into conscious perception, where they claim conscious perception starts at the global and coarse level before the local and detailed level.\n\nTaxonomy-based levels of categorization (“semantic categorization”; Rosch, 1998) was frequently used to study the content of rapid scene experience. The categories varied in hierarchies based on their degree of general-ness or specific-ness. In this categorization, the content of rapid scene experience can be reported either at the superordinate level or the basic level (Fei-Fei et al., 2007; Larson et al., 2014; Walther et al., 2009), but less likely at the subordinate level (Malcolm et al., 2012), with the subordinate level being the most specific category. Further evidence shows that the superordinate categorization is made prior to the basic-level categorization (Loschky & Larson, 2010; Sun et al., 2016). These findings provide evidence for the dominant view.\n\nOverall, studies in this field often used forced-choice discrimination tasks, such as identifying the same image through a series of rapidly presented images (e.g., Thunell & Thorpe, 2019), ascertaining the superordinate category (natural-ness, urban-ness) of a scene (e.g., Loschky & Larson, 2010), and determining if the briefly viewed images contain animals (e.g., Thorpe et al., 1996) or certain objects (e.g., Hollingworth, 1998). However, there are two methodological limitations in the forced-choice paradigm.\n\nFirst, the forced-choice paradigm restricts the response options. The studies that employ the forced-choice paradigm often implicitly assume that participants can only process the images at a certain level (usually coarse). Due to the limited response options, participants were unable to report detailed information about their experience even if they perceived it (Haun et al., 2017). Researchers may employ the forced-choice paradigm just for the sake of convenience. Other paradigms, such as free-report paradigms, are potentially more difficult to verify from a third-person view (Dennett, 2007).\n\nSecond, the forced-choice paradigms create expectations of the content of images that will be presented for participants. For example, asking participants to choose between “animal” and “non-animal” will tell them they might see an animal. This could help participants perceive more detailed information (McLean et al., 2021; Sun et al., 2017), while it can suppress seeing other aspects of rapidly presented scenes.\n\nTo overcome these problems, here we introduce a novel free-report paradigm. First, it addresses the restrictions on what participants can report. They freely reported what they saw in a briefly presented image and rated their confidence in the report. Second, to reduce any expectation that participants might have about the upcoming image category, we used a wide array of natural and artificial images (> 400) and did not tell participants any information about the types of the images that they will see or types of the responses that we expect from them.\n\nOf course, these modifications generate new challenges: how can we scientifically investigate such unconstrained data? What can we do to eliminate bias from us, the experimenters, on what participants should report? Rather than manually going through each image to define the correct answers, we utilize the majority vote of the participants. In other words, based on a large baseline of what participants report, we quantify the degree of specificity of reported words, which we call “intersubjective agreement (IA)”. For this purpose, we recruited a large pool of 670 participants. With our novel index applied to the free-report paradigm, we reexamine the dominant view that the content of rapid scene experience is limited to coarse information lacking in detail. The current study will answer if people can consciously see and report the details of an unexpected image at a brief glance.\n\n\nResults\n\nTo summarise, our novel index quantifies how “specific” a response is, with respect to a certain image. IA ranges from 0 to 1. A high IA means the word is specifically reported under the target image and not reported under other images, signifying detailed information. A low IA (~0.5) means the word is reported nonspecifically for all the images, signifying coarse information.\n\nFigure 1(a) explains the time course of one trial in our experimental paradigm (see also Methods). Upon brief exposure to an image, participants typed five words in the response box with confidence indicated in each word (See (b) in Figure 1). We tested 670 participants online.\n\na) Time course of a single trial. b) The response screen. The instruction said “For a guide, here are the kind of words that you may enter: 1, must be a non-repeat and valid English word; 2, nouns (e.g., ball, cat, apple), verbs (e.g., run, play, jump), adjectives (e.g., calm, exciting, beautiful); 3, please use the character ‘-’ if you enter a phrase with spaces, e.g., sunny-afternoon; if you are unable to come up with all 5 words, please enter arbitrary words and select the button ‘Don’t know’ for the rest”.\n\nTo quantify the degree of “specificity” of a reported word on a given image, we compare the report frequency of the word between the target image and the rest of the images. We call the index “intersubjective agreement (IA)” because it describes how well the reported word agrees with what other participants reported on that image but not on the other images. We refer “Word IA” to the IA associated with a particular word.\n\nWith our IA index, we do not need to assume any a-priori correct answers. A word response that has high Word IA with respect to an image indicates that the word is highly specific to the image, compared to the rest of the images.\n\nFigure 2 explains the steps involved in calculating Word IA under a particular stimulus onset asynchrony (SOA). Word IA is defined on a particular image and a particular word. Let us explain the case using a target image in Figure 2(a) and a word response “eiffel-tower” from participant 1 in Figure 2(b) (red solid box; For details, see Methods: Calculation of Word IA for each SOA). Figure 2(b) represents words reported by ten participants after viewing the target image for 67 ms.\n\na) The image used in this example. b) The 50 words reported by 10 participants, color-coded by confidence ratings. SOA = 67 ms. c) The cumulative percentage (y-axis) of the other images (i.e., all other 419 images we tested; red) as a function of the percentage of participants who reported the target word (x-axis, note in the descending order from 100% from left to 0% to the right). Here the target word is “eiffel-tower”. This curve serves as the baseline report frequency of the target word. The green curve shows the same for the target image, which jumps from 0 to 1 at X = 56%, reflecting the fact that 5 out of 9 “other” participants who saw this image for 67 ms reported “eiffel-tower”. d) The Receiver Operating Characteristic (ROC) curve constructed based on two cumulative curves in c. To construct the ROC, we shifted the criterion. We plotted the cumulative percentage for a pair of the within-image (green) as y-coordinate and other-images (red) as x-coordinate across all criteria.\n\nHere, ‘eiffel-tower’ was reported by five out of nine “other” participants (= 56%).\n\nNext, we estimate the baseline report frequency of the word “eiffel-tower” after seeing any one of the other images. Under SOA = 67 ms, no one reported the word “eiffel-tower”.\n\nWe convert the count into percentages and calculate the cumulative percentages for within-image and other-image counts to obtain Figure 2(c) (green for the target image and red for the other images).\n\nFrom this cumulative percentage, we construct the Receiver Operating Characteristic (ROC) curve (d) in Figure 2 and calculate the Area Under the ROC Curve (AUC). Supplementary Table 1 shows the cumulative percentage used to compute Figure 2(c) and (d). Supplementary Figure 1 shows the cumulative curves and ROC curve of another response word “grass” after viewing (a) in Figure 2.\n\nFinally, we repeat the steps above for each “eiffel-tower” reported by different participants under SOA = 67 ms and calculate the final Word IA value (SOA = 67 ms) of “eiffel-tower” under (a) in Figure 2 by averaging the AUC values.\n\nNote that a word must be reported by at least one “other participant” (i.e., reported by two or more people in total) under the target image to have a valid Word IA value. The words that were reported by only one person are called “rarely reported words”. We will explain more later.\n\nSimilar to Word IA for each SOA, we can also calculate Word IA across SOA (see Methods: Calculation of Word IA across SOA for details). In the following sections, we will first introduce the results from Word IA across SOA. This measures the specificity of response words robustly based on as many observations for each image. After that, we will compare Word IA between SOAs.\n\nMost words that were reported had very high Word IA across SOA. Over 9,463 words and 420 images, Word IA was distributed with the mean (± std) as 0.89 (± 0.16) and median (25%, 75%) as 0.96 (25%-tile 0.85 to 75%-tile 0.99) (Figure 3). Thus, upon seeing a totally unexpectable image, people freely report five unique words that are rarely used to describe any other images in our set.\n\nX axis is the report frequency of a word under a certain image (maximum = 30). Y axis is the Word IA values. The overall distribution of report frequency and Word IA is shown next to the axis.\n\nA traditional account of rapid scene experience predicts that people perceive a global and coarse description of the image upon brief seeing. If participants’ vocabulary is strongly confined to those global and coarse descriptions, Word IA should be low because those descriptions would be shared across images.\n\nHowever, upon examination of each reported word in Figure 2 as well as Figure 3’s distribution, this is unlikely the case. First, Figure 2(b) contains the words that would be normally regarded as global and coarse gist descriptions (e.g., clear-sky) but also local and specific words (e.g., eiffel-tower, paris). While the former types of descriptors are expected to be reported for the rest of images, the latter are unlikely to be reported. Thus, Word IA should be lower for the former and higher for the latter. Very high Word IA in Figure 3 implies that participants’ vocabulary is not confined to global and coarse descriptions.\n\nTo understand how the nature of the target image affected Word IA, we calculated the mean of Word IA (across SOA) for all words reported on a particular image. We call it Image IA. Image IA estimates the consistency and selectivity of the reported words for a particular image.\n\nFigure 4(a) and (b) list the five images that had the highest (and lowest) Image IA (across SOAs) among 420 images, respectively.\n\nFive words with highest and lowest Word IA are also shown. The Word IA of all response words in (a) is 1. The figure shows that both images with highest and lowest Image IA have words whose Word IA is close to 1, accompanied with high confidence rating. The images in (b) have lower Image IA because they also have words with low Word IA. Fre. means the frequency of the word being reported (maximum = 30). Con. means the mean confidence ratings of the word across participants who reported it.\n\nThe five images in Figure 4(a) had the mean Word IAs across all reported words to be 0.98 to 1. This means that a set of reported words for each of these images were extremely specific and almost never used to describe any of the rest of the images.\n\nFor example, the top image with Image IA = 1 was the letter array, typically used in the so-called Sperling paradigm in psychology (Sperling, 1960). This type of image is often used to demonstrate the limit of what people can report upon seeing an image in a brief moment. Here, the reported words are almost always a single letter (e.g., U, P, L, etc) that was actually contained in the array. Note that these words were reported spontaneously without warning participants that they will be tested with these types of arrays. In fact, if anything, this image was included among 20 other natural scene images, thus participants would have had very low expectation in seeing anything like this (see Discussion: Elimination of expectation).\n\nThe rest of the top images with high Image IAs were all natural scenes. Among those words, although there are a few arguable ones, such as Text (11 out of 30 people reported) and Word (19), most words were local and detailed, including: Mum (9), Apron (4), Boat (24), Speedboat (3), and Life-vest (2), etc.\n\nFigure 4(b) lists the five images that had the lowest Image IAs, ranging from 0.78 to 0.8. These scenes appear difficult to describe in words compared to the top images in Figure 4(a). Nonetheless, each image was reported with words whose Word IA was close to 1. This means that people agreed in describing these images with these highly specific words. Some of those words might be argued as global and coarse, such as Street (11), Tall (4), Natural (3) and City (12), whereas other words are more local and detailed, such as Ball (15), Crane (3), Dig (2), Drill (6), and Skyscraper (2). For these global and coarse words in Figure 4(b), we surmise that there are not many salient visual objects for detailed reports in the images. Thus, participants resorted to coarse descriptions, which are strongly shared by other people. As a result, the report frequency of these coarse descriptions are much higher than those for the rest of images, attaining high Word IA values.\n\nLower Image IA for Figure 4(b) is due to the result of many words that have lower Word IA, which were included to compute Image IA. There are some global and coarse words that can also be used to describe other images, such as Nature (2), Water (2), Sea (2), and Sky (3). There are also some meaningless words whose confidence rating is 1, such as “Na”, “Arbitrary”, and “None”, which are shared across images (i.e., low Word IA). The presence of these words indicates that some participants found it hard to describe the images using five distinct words. This is either due to the difficulty of the description of the image per se or due to the restriction of image viewing time, which we will investigate next.\n\nComparing the words whose Word IA is close to 1 in Figure 4(a) with those in Figure 4(b), we notice that the confidence ratings in Figure 4(a) tend to be higher than those in Figure 4(b). But the confidence ratings of the words with highest Word IA are much higher than those of the words with lowest Word IA within Figure 4(b), implying some correlation between confidence ratings and Word IA, which we will investigate next as well.\n\nWe also analyzed the proportion of rarely reported words (the second column from the left for Figure 4(a) and (b). They were not included in the calculation of Image IA because their Word IA was not defined. If a word was reported by only one person, it could be truly a unique word to describe that particular image, but it could also be a random response that was not elicited by the stimulus images. A higher proportion of rarely reported words could indicate that it is harder to perceive describable information from the image. To test that, we computed the proportion of rarely reported words for each image, but we found no correlation between it and Image IA, r = -.06, df = 418, p = .195, 95%CI = [-0.16, 0.03]. Whether rarely reported words are not random responses can be addressed in the future studies by recruiting a larger number of participants.\n\nAs implied in Figure 4, high Word IA tends to be associated with high mean confidence ratings. If this correlation is reliable, Word IA can be taken as a proxy of conscious perception, reflecting metacognitive access to what participants see phenomenally (Matthews et al., 2018; Seth et al., 2008).\n\nFigure 5 shows the scatter plot of Word IA (across SOA) and mean confidence rating for each word, with the distributions of those variables. There was a significant correlation between Word IA and mean confidence rating for each word, r = 0.33, df = 9461, p < .001, 95%CI = [0.32, 0.35]. Thus, our Word IA measure captures an aspect of conscious perception, that is, the degree of confidence they have in reporting what they see.\n\nX axis is the mean confidence (across participants who reported the word) for each word. Y axis is Word IA. 95% CI is also shown (gray shade).\n\nIt is plausible that the association between high Word IA and high confidence rating in Figures 4 and 5 are artefacts of our grouping of SOA. At longer SOAs (133 or 267 ms), it is likely that participants see details clearly and consciously with high confidence with high IA. At short SOA (67 ms), they might not see much and report random words with low confidence with low IA. Such results would inflate the correlation between Word IA and confidence ratings. To rule out this possibility, we examined the correlation at each SOA.\n\nHowever, even under the shortest SOA (= 67 ms), there was a significant correlation between Word IA and confidence rating: r = 0.43, df = 9330, p < .001, 95%CI = [0.41, 0.45] (Figure 6(a)). Figures 6(b) and (c) show the data for longer SOAs, which also showed significant correlations between confidence and Word IA: at SOA = 133 ms, r = 0.37, df = 11046, p < .001, 95%CI = [0.35, 0.38], and at SOA = 267 ms, r = 0.34, df = 11664, p < .001, 95%CI = [0.32, 0.35]. Therefore, confidence rating was correlated with Word IA at all three SOAs.\n\na-c) The dot plots with jittering for confidence ratings. Note here, each dot represents a confidence rating from one participant for a given word. Word IA at SOA = 67 ms (a), 133 ms (b), and 267 ms (c). X axis is confidence rating. Y axis is Word IA.\n\nTo control the difference among participants and images, we analysed the data with four multilevel regression models with the random effects being intercepts for participants and images. Our first model (Model 1) is the null model which only included the random effects of intercepts, adjusted Intraclass Correlation Coefficient (ICC) = 0.248, AIC = 57737, BIC = -57703. Our second model (Model 2) added the fixed effect of confidence rating on top of Model 1, adjusted ICC = 0.221, AIC = -61941, BIC = -61899. It showed that Word IA for each SOA can be explained by confidence rating, p < .001. The third model (Model 3) added the fixed effect of SOA on top of Model 2, adjusted ICC = 0.222, AIC = -62093, BIC = -62043. It showed that Word IA for each SOA can be explained by both confidence rating (p < .001) and SOA (p < .001). The fourth model (Model 4) is the full model which added the fixed effect of interaction between confidence rating and SOA on top of Model 3, adjusted ICC = 0.222, AIC = -62265, BIC = -62206. It showed that Word IA for each SOA can be explained by confidence rating (p < .001), SOA (p < .001), and the interaction between them (p < .001). According to the AIC and BIC of these models, Model 1 is the worst model, whereas Model 2, 3, 4 are similar, with Model 4 having the lowest AIC and BIC. However, according to the likelihood ratio test (Winter, 2013), there was a significant difference between Model 2 and 3, χ2 = 153.81, df = 1, p < .001. There was also a significant difference between Model 3 and 4, χ2 = 173.75, df = 1, p < .001. Therefore, Model 4 is the most preferred model, whose parameters are shown in Supplementary Table 2.\n\nFinally, we present somewhat unexpected, yet striking findings based on further analyses of two sets of images: highly similar image pairs and artificial image pairs.\n\nAs explained in Methods, we filtered the identical images over the available image sets (screenshots from videos) with both automatic and manual procedures. However, unintentionally, we retained 22 pairs and two trios of highly similar but slightly different natural images; see a) in Figure 7 and Supplementary Figure 2. Rather than removing the data from these images, we analyzed them with our analysis method to test its validity.\n\na) Four example pairs of the highly similar natural images, including the pairs with lowest (54) and highest SSE (362). For all highly similar natural images, see Supplementary Figure 2. b) An example plot of the frequency of all the unique response words from a pair of highly similar images. X axis is the frequency of response words from one image obtained from a set of N=30 participants. Y axis is the frequency of response words from the other similar image obtained from a separate set of N=30 participants. Each data point means a response word. The solid line is y = x, which means perfect consistency. c) The distributions of Sum of Square of Error (SSE) of pairs of two similar natural images (green) and artificial images (red). As baseline (blue), we computed SSE for randomly selected two images. X axis is SSE, which is the sum of squared distance between each data point and the y = x line in (b). Y axis is the probability density. 99%CI is shown by the line segment. d) SSE computed for four pairs of artificial images.\n\nFor simplicity, we removed one image from each trio and got 24 pairs of natural images in total. To quantify the degree of the similarity of free reports between two similar images, we computed “sum of square of error (SSE)”. In short, SSE quantifies the similarity of the frequency of reports between two images presented to two separate populations of participants (see (b) in Figure 7). SSE is 0 when the reports are identical. It is expected to become large if it is computed between two different images.\n\nThe green line in (c) in Figure 7 demonstrates that two groups of participants gave a very similar set of words for these two similar images. This contrasts with the baseline (blue), where SSE is computed between randomly paired two images (for details, see Methods - Data analysis - shuffle the pairs of similar images). The fact that two distinct groups of N=30 participants responded highly similarly to the pairs of highly similar images lends support to our assumption for the IA measure: upon seeing similar images, a population of people give similar responses even when measured with an unconstrained free-report paradigm.\n\nSecondly, we analysed the four pairs of artificial images (see (d) in Figure 7 and Supplementary Figure 3 for details), which have been used in previous psychophysical experiments. Unlike natural images, we suspected that if these artificial images are presented to participants without any warning or expectation, they may not be able to see the contents very clearly (see Discussion). As we expected, participants did not really spontaneously report particular details of each simple image, which differentiates them (e.g., left vs. right, colored vs. black-and-white, high vs. low spatial frequency, left- vs. right-tilted). This is totally understandable given that these features only make sense when these pairs were presented in contrast and participants are invited to report their differences. Their spontaneous reports are more to do with the common attributes for these pairs, resulting in lower SSE.\n\nOne exception to this rule was the pair of the Sperling letter array, one of which was indeed featured in Figure 4(a), which achieved the highest Image IA among all the tested images. We expected that the dominant responses for these types of the images would be global and broad descriptions, such as “letters”, “alphabets”, but rarely the actual single letters, such as “U” or “A” (Haun et al., 2017). Contrary to our expectation, each letter was reported rather frequently as shown in Figure 4(a) and Supplementary Figure 3. This is quite remarkable, given that in our experiment, participants were never told about this type of stimuli (see Discussion: Elimination of expectation). As a result, the SSE between the paired Sperling images (= 302) was much larger than the other three artificial image pairs (60-130).\n\n\nDiscussion\n\nIn the present study, we used a free-report paradigm (Figure 1) to examine a widely-supported view on rapid scene experience. In a traditional view, people are expected to process and report coarse, but not detailed, information about a briefly presented scene. Rather than presuming what words should qualify as “correct” answers, we used the words that other participants reported about the same image as the expected report. Based on this notion, we proposed a novel measure, termed “intersubjective agreement” (IA) (Figure 2). Word IA quantifies the specificity of a response word, by comparing the frequency of the response word under a given image with that under all other images. The frequency of the latter serves as the baseline report of the response word. With our IA measure, we demonstrated that participants report words that are maximally specific (IA = 1) across SOAs (as short as 67 ms) (Figures 3, 4). Further, we demonstrated Word IA computed across SOA and at a given SOA showed correlation with confidence ratings, thus reflecting the degree of conscious access (Figures 5, 6). The analysis of highly similar images (Figure 7) assured the validity of our paradigm. Our results challenge the notion that reports on a briefly viewed scene are coarse and not detailed.\n\nFree-report paradigm with our novel IA measure. While the forced-choice tasks have revealed a great deal about various limits and scopes of the human visual system in rapid vision, they do not allow us to make inferences as to whether participants perceive more than what experimenters expected. Importantly, our paradigm is free from such a restriction imposed by us, the experimenters.\n\nOur study is not the first application of the free-report paradigm to examine the nature of rapid visual perception. In a pioneering study, FeiFei et al. (2007) asked participants to write a short paragraph to describe the image of everyday scenes after briefly viewing it for 27 ms to 500 ms (masked). The responses were then analyzed by 5 scorers. Unfortunately, they introduced experimenters’ bias at this evaluation stage. Specifically, the experimenters asked the scorers to evaluate if the response paragraph contained objects that they, the experimenters, defined for the scorers. As such, the objects that were not included in the experimenters’ preset objects were not analysed.\n\nAnother issue of such assessor-based scoring is that the subjective experience of scorers is quite different from that of participants. In FeiFei et al. (2007), the raters saw the target image for a long duration moving their eyes to inspect various parts of the images. However, the participants in the main experiment saw the images briefly with minimal saccades. Thus, we cannot interpret what the participants actually experienced based on the scorers’ evaluations.\n\nWe minimised these sources of experimenters' biases and confounds. We analysed all that participants reported about their experience based on what other participants reported in the same viewing condition. Importantly, our novel strategy can scale like forced-choice paradigms without manual inspection. With more participants per image set, our estimate becomes more robust.\n\nAlthough not directly comparable, some of the previous forced-choice paradigms studied aspects of rapid scene experience. For example, Biederman et al. (2006) and Larson et al. (2014) showed that participants’ responses were more accurate under a longer SOA. Similarly, in our study, Word IA for each SOA was positively associated with SOA (Supplementary Table 2). Importantly, this increase in IA was also accompanied with the increase in confidence and frequency of reports, consistent with previous studies as well (e.g., Fu et al., 2016).\n\nTo enhance these strengths, we employed an online experimental platform to recruit a large number of participants and to use a large set of stimuli. They are important prerequisites of our novel IA measure and our free-report paradigm. Note that in our preliminary experiment, we did not see any qualitative difference in the results between in-lab participants (N=10) and online participants (see Supplementary Figure 4).\n\nElimination of expectation. Another important extension is that our paradigm does not allow participants to expect what category of images will be shown. In previous studies, participants were told that the images would be one of a few categories (e.g., animal vs. non-animal; Fabre-Thorpe et al., 2001). High accuracy in rapid scene processing (e.g., Evans & Treisman, 2005; Fabre-Thorpe et al., 2001) may depend on expectation (McLean et al., 2021; Sun et al., 2017). In our paradigm participants could not expect the images, yet they still reported impressive details of the briefly presented images.\n\nConfidence rating correlates with Word IA. Surprisingly, the detailed information accompanied with high confidence across images (Figures 4, 5 and 6).\n\nThe results with Sperling arrays (see Figure 4) were rather notable. Without any expectations, participants reported specific letters, which goes against an idea that conscious perception strongly depends on expectation (Mack et al., 2017; Pinto et al., 2015). Note these specific letters reported with high confidence were the ones that were included in the array.\n\nSpeaking of confidence rating, we are not aware of other studies that asked participants to provide confidence ratings together with words in a free-report paradigm. Our study is perhaps the first that combined a free-report and confidence rating. The words with high confidence were more specific and shared between participants (Figures 4, 5, and 6). If we consider what participants reported in this study as a “gist” of a scene, we can interpret it to mean that gists are something that we can metacognitively monitor and consciously access. In light of past studies that showed gists can be grasped without attentional amplification (Li et al., 2002; Mack & Rock, 1998), this further supports the notion that conscious perception does not always require attentional amplification (Koch & Tsuchiya, 2007; Tsuchiya & Koch, 2016). Our study extends this notion with freely-reported image contents without expectation.\n\nImportantly, we observed highly specific words (IA = 1) even in SOA = 67 ms condition (77% of images). Many specific words came with the highest confidence of 5. Non-specific words (IA < 0.6) were observed much less frequently across SOAs (30% for SOA = 67 ms, 19% for SOA = 133 ms, 17% for SOA = 267 ms). We predict this pattern of results would not be observed if the image was strongly masked to make the image invisible (Kaunitz et al., 2011). Taken together, our findings require the revision of rapid scene experience from traditional “coarse and nonspecific” to “detailed and specific even without expectation”.\n\nWhat is the potential source of the discrepancy between ours and traditional findings? Given that we obtained similarly high IA for both artificial (letters) and natural stimuli, the source of discrepancy is unlikely to be solely due to the type of the stimuli.\n\nInstead, we point out another important feature of our task. In our task, we never repeated the same image for a given participant. We suspect this is one source of the discordance as previous studies tended to use the same stimuli across trials (e.g., Kimchi, 1992; Navon, 1977). As Endress and Potter (2014) suggested, repeated presentation causes prospective interference, possibly biasing our attention and expectation to the features that distinguish trials (see also Kaunitz et al., 2016). It is worth revisiting previous studies but using stimuli that are never repeated across trials.\n\nA remaining question is: what is the minimal duration that is required for such rapid recognition? When we designed this study, we were not confident if the online study can achieve reliable presentation of short duration stimuli. Thus, we opted for going rather conservative durations of 67 ms as minimal. Further, we did not expect that participants could make detailed word reports that correlate with confidence. Therefore, we did not push the limit. Future studies can test much shorter duration.\n\nOur novel paradigm with IA measure is highly adaptable for different research purposes. For example, any future researchers can use our current data as the normative data (our data is fully and freely available online for both the image sets [https://osf.io/q2cr8/] and the response words [https://osf.io/7spxd/]). Using them as the baseline, it would be easy to perform a study to test if some population of patients with known mental disorders, such as schizophrenia, would see and report the same words as the healthy population. Future studies could also utilize different stimulus sets to address different questions. For example, if we change the nature of the stimulus set into emotional movies (e.g., Cowen & Keltner, 2017), we can characterize commonality and differences of the nature of emotional experiences using free report paradigms without imposing any theoretical assumptions introduced by us, the experimenters. Also, the emotional intensity within each movie can be calculated using normative ratings of lexico-semantic factors (e.g., valence and arousal; Mohammad, 2018).\n\nAnother possible future direction is to measure the amount of information participants can perceive from a brief glance, using a task that is similar to Sperling’s partial-report paradigm. We can show participants a natural scene image for a short amount of time, randomly select a few response words under that image from the present study, and use them as stimulus words to ask participants if those words can be used to describe the image.\n\n\nMethods\n\nWe recruited 801 online participants from Amazon’s Mechanical Turk (MTurk) who had a Human Intelligence Task (HIT) approval rating of more than 97% and more than 5,000 approved HITs. Among them, 131 participants did not complete the task and were excluded, leaving 670 valid participants. MTurk has demonstrated its reliability and validity (Sheehan, 2017) by replicating lab effects in many research areas (Amir et al., 2012; Crump et al., 2013; Klein et al., 2014; Paolacci et al., 2010). Participants read the online explanatory statement and gave informed consent by pressing a key before they began the experiment. Each participant received US$3 as compensation for their time (30 minutes). Upon completion of the experiment, participants answered a few demographic questionnaires. Within the questionnaires, participants were allowed to answer ‘NA’ if they wished. We used TurkPrime (Litman et al., 2017) to manage the recruitment and payment of participants from MTurk. Supplementary Figure 5 shows the demographics (sex, age, nationality, first and second language, number of years speaking English) of the participants. Ethics approval was obtained from the Monash University Human Research Ethics Committee (approved project ID 17674).\n\nTo create the online experiment, we used InquisitLab and InquisitWeb (version 5; Software, 2018). Inquisit’s software provides highly accurate stimulus presentation time (within milliseconds; De Clercq et al., 2003). To minimise the effect of a slow network, we asked participants to download the software package of InquisitPlayer, which then downloaded all experimental files to their computer before the experiment. During the experiment, InquisitWeb blocked the participant from interacting with other software programmes on the same computer, reducing the likelihood of poor data quality due to distractions. The functions of above software can be equivalently performed by PsychoPy and Pavlovia.\n\nOne of the authors (SN) captured 9120 still-frame naturalistic images from a series of online videos at Videoblocks. Each coloured image was in JPEG format with a resolution of 1920 × 1080 pixels. As a video contained multiple still-frame images captured within a one-second interval, some pictures were highly similar. After filtering the identical images, we obtained 570 images.\n\nAmong these images, we randomly selected 415 images for our experiment (shown in Supplementary Figures 6a - 6f). Among them, three images were used as practice images. In addition, we included eight images (four pairs) of artificially generated images to represent typical stimuli used in psychophysics experiments (i.e., random noise, Gabor patch, Sperling letter array (Sperling, 1960), a red circle; see (d) in Figure 7 and Supplementary Figure 3). As a result, we had 420 experimental images and three practice images. We randomly divided the experimental images into 20 blocks each with 21 images. Each participant saw the three practice images and a block of 21 images.\n\nUpon downloading the InquisitPlayer, the experiment began with a consent form. After giving the consent, participants received an instruction on how to perform the task. They were told that in each trial, they would briefly see an image. Their task was to enter five valid English words without any repeats to describe their impression of the image. They were allowed to use nouns, verbs, and adjectives. They were reminded of this instruction while they typed the words in each trial (see (b) in Figure 1). Upon these instructions, participants practiced the task for three trials (with the same three images across participants). The stimulus onset asynchronies (SOAs) for these trials were randomly assigned from 67, 133, or 267 ms, one trial each. These images were not analysed.\n\nEach participant was tested in one block that contained 21 trials. Figure 1 shows the time course of a single trial, which started with 1 second of fixation, followed by a target image. The target image was shown for a variable duration until the five successive masking images, each presented for 60 ms. SOA between the target and the first mask was either 67 ms or 133 ms or 267 ms. Each mask was an image with 1920 × 1080 pixels, which we constructed by filling it with 16 × 16 pixel image patches randomly taken from the 420 experimental images.\n\nAfter the mask, participants were presented with the response screen (see (b) in Figure 1). Participants gave give response words as instructed and rated how confident they were in seeing each word in the image (1: Don’t Know, 2: Guess, 3: Maybe, 4: Confident, 5: Very Confident). The response screen restricted participants to enter only alphabets and numerics. They were not allowed to use the empty space and asked to use a hyphen (‘-’) instead. If participants could not come up with 5 words, they were instructed to enter an arbitrary word with “Don’t know” as the confidence rating.\n\nFor each participant, we tested seven trials for each SOA (66 ms, 133 ms, and 267 ms), whose order was randomised across participants. Across 21 trials, participants never saw the same image more than once. For a given block of 21 images, we aimed to test a cohort of 30 participants so that each of the 21 images was presented to at least 10 participants at each SOA. Sometimes, MTurk recruited more than 30 participants. When this occurred, we took the first 30 participants’ data for the subsequent analyses.\n\nWe performed minimal curation on the reported word as we did not want to inject our own bias into the data set. We provided all raw data so that researchers can examine the effects of any curation on our result. Our minimal curation procedure included the following.\n\nIf a participant entered the same word for a single image more than once, then we took only the first one with its confidence rating, and removed the second response (or later) from the analysis.\n\nFor each word, we applied three pre-processing steps. First, we converted the words to lowercase using the R package tm version 0.7-8). Second, we corrected misspelled words semi-automatically using the R library hunspell version 3.0) package (if the spell checker returned with one suggestion, we adopted it if relevant. Otherwise, we manually inspected the alternate suggestions and picked the most appropriate one). Finally, we performed word-lemmatisation using the R-package textstem version 0.1.4). Word-lemmatisation grouped similar words (e.g. plurals, verb tense), such as “child” and “children”, “walked” and “walk”, into a single base-form word so that the subsequent analysis would consider them as the same word.\n\nAfter all these steps, we obtained 63,000 word responses (i.e., 420 images * 3 SOAs * 10 participants * 5 words) for the subsequent analysis. After combining the same words under the same images and the same SOA, we had 41,170 unique words. These word responses along with associated confidence ratings are available as a CSV file at https://osf.io/7spxd/.\n\nCalculation of Word IA for each SOA. For each target image at a given SOA, there were 10 unique participants who saw it. For each of 50 reported words, we went through the following processes. First, we counted the number of participants out of the rest of nine participants who reported a target word. Second, for each of all other 419 images, at the same SOA condition, we counted the number of nine participants who reported the target word. We excluded one participant that has the same participant order for the other images to equate the number of the participants for this counting to be 9 per SOA. Third, based on the number of these participants, we computed % of report and % of cumulative report for both the target image and all other images (Supplementary Table 1). From these, we applied the logic of Signal Detection Theory (Green & Swets, 1966; Macmillan & Creelman, 2004). We used the cumulative frequency of reports to construct the receiver operating characteristic (ROC; see (c) and (b) in Figure 2. Fourth, we calculated the area under the ROC curve (AUC). If there were more than one participant who reported the same target word, we went through the same procedure and computed the mean AUC across them as Word IA at that SOA.\n\nAs we explained in the Results section, if the target word was reported only by one participant among 10 participants, it is called “rarely reported word” and its Word IA is not defined. Among the 41,170 unique (word, image, SOA) groups, 30,954 of them were only reported by one person and therefore didn’t have a defined Word IA, which left us 10,216 response words with a valid Word IA.\n\nCalculation of Word IA across SOAs. We also computed Word IA by pooling the responses across SOAs. We did this to reduce the possibility of rarely reported words and to estimate the baseline rate of the reported words more robustly.\n\nWe performed the same analysis as Word IA for each SOA with the following exceptions. For each target image across SOAs, we had 30 unique participants who saw it, resulting in 150 reported words. For Word IA across SOAs, we counted the number of participants out of the rest of 27 participants who reported a target word. We removed one participant from each SOA group so that across SOAs analysis is not biased. Similarly, we did so for 27 participants to estimate the baseline with the other images. Other aspects of the calculation were the same as Word IA for each SOA.\n\nAmong the 30,911 unique (word, image) groups, 21,448 of them did not have a defined Word IA, which left us 9,463 response words that had a defined Word IA.\n\nExclusion of similar images in Word IA calculation. Although we tried to filter highly similar images, we noticed there were still some highly similar (but slightly different) image pairs in our image set (Supplementary Figure 2). While none of these pairs was presented to the same participant, word responses generated from these images could affect Word IA. For a given reported target word, the Word IA for one of the similar paired images will be generally lower because the target word is likely to be reported under the other paired image. To reduce the effect of this problem, when calculating the Word IA of responses to one of these images, we excluded the paired image from the baseline.\n\nMultilevel regression models. The models were performed using the “lme4” package in R. The parameters were estimated using the maximum likelihood (ML) method.\n\nShuffle the pairs of similar images. To compare the consistency between pairs of highly similar images with random image pairs (in Results section: Beyond global and coarse reports revealed by Word IA), we constructed a “null distribution” as the baseline using a bootstrap way. We randomly selected one image from each of the 24 pairs and paired it with another image that was randomly selected from the 48 natural images (i.e., the 24 pairs of highly similar images). So, we obtained 24 random pairs of images. We then calculated the SSE (see Results section) of each pair and the mean of the 24 pairs. We repeated this process 100 times to obtain the “null distribution” of SSE.\n\n\nConclusion\n\nContrary to a widely supported view that participants are more likely to perceive coarse information from a briefly presented natural scene image, we found that participants reported highly detailed descriptive words with high confidence. Our findings show that even without expectation, a brief glance of scene images is enough to provide us with a vivid conscious experience which can be metacognitively monitored. Our novel paradigm and measures can lead to an exciting avenue for future research that finds intersection on sensory psychology, big data, cognitive-linguistic and consciousness research.\n\n\nData availability\n\nOSF: Human Annotations with Confidence Ratings on Natural Images. https://doi.org/10.17605/OSF.IO/7SPXD (Chuyin, et al., 2021)\n\nThis project contains the following underlying data\n\ngist_batch_v1_all_mt_raw.csv (the raw data)\n\ngist_batch_v1_all_mt_summary.csv (all the participants who signed up the study on MTurk)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nOSF: Natural Scene Images for the IA paper. https://doi.org/10.17605/OSF.IO/Q2CR8 (Nishimoto et al., 2021).\n\nThis project contains the following extended data\n\n587 natural scene images in JPEG.\n\n8 artificial stimulus images in JPEG.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nOSF: Supplementary materials for the IA paper. https://doi.org/10.17605/OSF.IO/U6QPM (Chuyin, et al., 2021).\n\nThis project contains the following extended data\n\nSupplementary Tables and Figures.pdf (Supplementary Tables 1-2 and Supplementary Figures 1-6)\n\nSupplementary tables.xlsx (Supplementary Tables in Excel)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nExperiment code available from: https://doi.org/10.5281/zenodo.5794712 (Koh & mluu0010, 2021)\n\nProcessed data and analysis code available from: https://doi.org/10.5281/zenodo.5796303 (Chuyin & Koh, 2021)\n\nData are available under the terms of the Apache license 2.0.",
"appendix": "Acknowledgement\n\nA previous version of this article is published on PsyArXiv: https://psyarxiv.com/d2s38/ (https://doi.org/10.31234/osf.io/d2s38).\n\n\nReferences\n\nAmir O, Rand DG, Gal YK: Economic games on the internet: the effect of $1 stakes. PLOS ONE. 2012; 7(2). PubMed Abstract | Publisher Full Text\n\nBayne T, McClelland T: Ensemble representation and the contents of visual experience. Philosophical Studies. 2018; 176(3): 733–753. Publisher Full Text\n\nBiederman I: On the semantics of a glance at a scene. Perceptual Organization. 1981; 213: 253.\n\nBiederman I, Rabinowitz JC, Glass AL, et al.: ON the information extracted from a glance at a scene.2006. 1–4.\n\nCampana F, Tallon-Baudry C: Anchoring visual subjective experience in a neural model: The coarse vividness hypothesis. Neuropsychologia. 2013; 51(6): 1050–1060. 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}
|
[
{
"id": "120530",
"date": "07 Feb 2022",
"name": "Marius Usher",
"expertise": [
"Reviewer Expertise Cognitive psychology"
],
"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 examines the amount of information that observers can extract from visual images at very fast rates (67/133/267 ms masked). The researchers present a large set of complex scenes, which observers can not generate expectations about, and rely on a verbal free response method (rather than the traditional forced response) to obtain information about what the observers could extract from the brief and masked display. In order to quantify the accuracy of the responses the authors developed a novel index called Intersubjective Agreement (IA), which reflects the specificity of the responses to a target image. The results indicate that most of the responses show a high IA and correspond to visual details (small object, or letter in a scene), a finding which goes against the traditional wisdom that people can only extract broad (gist or category type) information from such brief displays. Moreover, the IA is correlated with confidence, indicating metacognitive conscious access.\nI find the question that this study addresses an important one and the method innovative and solid. The writing is also quite clear, so I believe this paper could be of interest to the research community. Below I will enter a number of comments, which the authors could address to make their paper more clear and easier to follow, and to explore its implications.\nMethods\np. 4. I wonder if the term Word IA, should be Word-Image IA (as it seems to link to a Image-word pair).\n\np. 5. \"Word-IA are high\". Is the point that the values are closed to 1? Is the possible range (0, 1)? It may help to specify this.\n\nFig 2c. There should be a legend for the colors here.\n\nAlso it would help to clarify the motivation why one has to rely on such a complex method (ROC curves) for the index, instead of just computing a ration of responses given to the target image over All responses (to all images). Usually ROC curves are used when there is a subjective-criterion difference. It was not very clear why this complex method was needed here. Finally, the construction of Fig 2c may be explained better. (Those cumulative probabilities appears to only have binary 0/1 values…)\n\nIt would help if one could also provide some index of the information that one can extract from the images. (Perhaps this could integrate the IA with the number of words reported…)\n\nResults\nThere are very interesting results reported here. But to me the most important would be to see how the information extracted from the image (see above) or at least the IA, varies with the presentation rate. While the paper reports that IA are high even at the fastest rate (67 ms), I did not see a Figure showing the dependency on the rate. Finally, it would be quite interesting to know what the temporal limit at which the capacity to extract information from rapid displays breaks down? (I suppose this will need to take place at fast enough rates, of < 20 ms or so). Showing such data will also help to better appreciate the results at 67 ms, as the more rapid presentation would serve as a control, relative to which the present results can be compared.\nImplications\nFinally, it may be interesting to discuss implications to theoretical debates such as the Overflow in Consciousness 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?\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": "8655",
"date": "24 Aug 2022",
"name": "Zhang Chuyin",
"role": "Author Response",
"response": "Thank you for reviewing our paper and providing valuable comments! We will respond your concerns one by one. 1, p.v4. I wonder if the term Word IA, should be Word-Image IA (as it seems to link to a Image-word pair). Reply: We agree with you that Word-Image IA is more precise and consistent with what we meant by Word IA. However, Word-Image IA is a bit long and the abbreviation of WIIA is not intuitive to grasp. On the other hand, Word IA is concise with a minimal use of abbreviations, IA. Thus, we opted for using Word IA throughout. We’ve added the following to make it clear: Footnote: \"To be precise, we should perhaps use “Word-Image IA” instead of “Word IA” as it links to an image-word pair. Just for the simplicity and readability, we use “Word IA”.\" 2, p. 5. \"Word-IA are high\". Is the point that the values are closed to 1? Is the possible range (0, 1)? It may help to specify this. Reply: Yes, the possible range of Word IA is [0, 1]. By “high” we mean the values are close to 1. We’ve clarified this as follows: Page 5: “as we mentioned above, Word IA ranges from 0 to 1. Most words that were reported had very high Word IA (close to 1) across SOAs.” 3, Fig 2c. There should be a legend for the colors here. Reply: Thank you. We’ve added in a figure legend for Figure 2c (and newly added e). We also paste the modified explanation of Figure 2 as follows: See Figure R1 linked here Figure R1 (Figure 2). e) Another example for the target word “grass” after viewing (a), whose Word IA = 0.84. They are constructed in the same way as (c) and (d). This example shows values on the red line are not binary. 4, Also it would help to clarify the motivation why one has to rely on such a complex method (ROC curves) for the index, instead of just computing a ration of responses given to the target image over All responses (to all images). Usually ROC curves are used when there is a subjective-criterion difference. It was not very clear why this complex method was needed here. Reply: We had empirical and theoretical motivations to introduce the ROC curves instead of a simpler method, like the one you suggested. Empirically, a simpler ratio scale is not easy to interpret. If we define it as: Ratio1 = # of responses given to the target / # of responses to all images (including the target), then, it ranges from 0 to 1. But the distribution is extremely concentrated around 0 and 1 (Figure R2). Theoretically, this method is problematic in that any word that was reported in many images, such as “grass”, can never obtain high value, even if one particular image was reported with “grass” for all of N = 30 people. If “grass” was reported 300 times in total, then this ratio1 index will be 0.1 (= 30/300). Thus, we need some way to normalise the baseline report rate of the word. See Figure R2 linked here Figure R2. Histogram for the distribution of ratio1 (X axis). Ratio1 = [# of responses given to the target / # of responses to all images (including the target)]. We calculated ratio1 for all unique (word, image) pairs. This leads to the 2nd type of ratio scheme, Ratio2 = % of responses given to the target / % of responses to all images (including the target). This comes closer to what our ROC is measuring. However, Ratio2 = [Xtarget/30]/[Xall/(420 × 30)] = (Xtarget/Xall) × 420 = Ratio1 × 420. Thus, it can go from 0 to 420 and interpretation of ratio 2 is even harder than ratio 1. We need some alternative methods. At first, we wanted to invent an index that is free of subjective criteria, or confidence rating, as you suggested, using ROC. Let us consider “eiffel-tower” in Fig 2a as an example. 13 out of 30 participants reported it under the target image, and 1 participant reported it under other images. Then, our implementation of the ROC goes as follows: Order the responses according to the confidence ratings to the target image, then to compute a cumulative probability. This serves like a cumulative hit in a standard ROC. (Figure R3a - green line) Repeat the same procedure as 1) but for all-non target images, which serves like a cumulative false alarm. (Figure R3a - red line) Construct the ROC. (Figure R3b) See Figure F3 linked here Figure R3. a) Cumulative proportion (y-axis) for the target (green) and other images (red). We first order the responses according to the confidence, and count the number of responses for each confidence rating. X axis is confidence rating. If participants did not report “eiffel-tower”, we counted them as 0 confidence rating response, so that cumulative proportion always reaches 1 for both hit (green) and false alarm (red). b) A ROC curve constructed from Figure R3a. X axis is the false alarm rate, which comes from the red line in Figure R3a. Y axis is the hit rate, which comes from the green line in Figure R3a. AUC here is 0.72. From the ROC, we computed the area under the ROC, which we call “AUC by confidence”. For the example of “eiffel-tower”, AUC by confidence = 0.72. We calculated AUC by confidence for every response word, compared against Word IA in Figure R4a. See Figure R4 linked here Figure R4. a) The scatterplot showing the relationship between Word IA (x axis) and AUC by confidence (y axis). Red line is the identity. b) The strong correlation between AUC by confidence and report frequency under the target image. c) Histogram of AUC by confidence (x-axis is the same as panel b). In Figure R3, we showed the cumulative proportions and their corresponding ROC. As we count the proportion of people who did NOT report “eiffel-tower” as confidence = 0, the maximum area under the ROC (regardless of the false alarm) is set by the % of people who reported “eiffel-tower” in the target image, which is 13/30 = 43%. This corresponds to the highest black point in Figure R3b on the y-axis. Although “eiffel-tower” was reported only 1 out of 419 images × 30 responses (nearly 0 false alarm), this means that “eiffel-tower” can attain only up to AUC of 0.72. This means, generally speaking, AUC by confidence can reach 1 when and only when all 30 participants reported the word under the target image. Figure R4a shows a moderate positive correlation between AUC by confidence and Word IA. However, Figure R4b shows an extremely tight correlation between AUC by confidence and the report frequency of the word for the target image. In the case of the “eiffel-tower”, the report frequency of 13 (out of 30) indeed predicts AUC by confidence at 0.72. As a result, their distributions are quite different. AUC by confidence is highly concentrated around 0.55 (Figure R4c). Another feature we see in Figure R4a is that AUC by confidence hardly goes below 0.45. This is because our participants rarely reported the same word across many images. In other words, the baseline report rate of any given word is very low. Among all reported words, “man” was reported most frequently, but it was only around 12% of possible report rate (around 1600 times, out of the possible 420 × 30=12600 times in total under all images). This leads to our proposal of IA. Figure 2c in the main text shows that we use % of participants for cumulative probability to construct ROC. This allows us to characterise a word such as “eiffel-tower” with IA~1.0, which signals that this word is effectively used for this image, but not for the other images. This also explains why in Figure R4a, we see many words with AUC by confidence of ~0.6-0.7 having Word IA of 0.75-1.0. Given the importance of explaining the motivations behind our new IA measure, we decided to include this as a supplementary material. We explicitly mentioned this in the Results section as follows: Footnote: \"We described our motivations and rationale behind our definition of IA over other simpler methods, such as ratio of reported words for the target vs all images in Supplementary Material (see https://osf.io/nvfhs).\" 5, Finally, the construction of Fig 2c may be explained better. (Those cumulative probabilities appears to only have binary 0/1 values…) Reply: You are correct in pointing out that both green and red lines in Figure 2c go from 0 to 100%. As long as we do not group multiple images as a target image, the green line always goes from 0 to 100% as it shows the cumulative probability of hit. The red line (other-image) might be different for other examples. We’ve added Figure 2e and 2f (example of “grass”) to show that cumulative possibilities on the red line take values between 0 and 1. This is because the word “grass” was reported in many images with different frequencies (50%, 30%, …). We’ve also added a sentence into the legend of Figure 2c as follows: (Figure 2c) “The value on this curve doesn’t have to be 0 or 1, it jumps from 0 to 1 because no one reported “eiffel-tower” under the other images. ” 6, It would help if one could also provide some index of the information that one can extract from the images. (Perhaps this could integrate the IA with the number of words reported…) Reply: We agree with you that it would be great to come up with some index of information that one can extract from a given image. In our results section, we proposed “Image IA” as such an estimate. Image IA is the mean of Word IA under a specific image. Thanks for your suggestion to integrate IA and the number of words reported, which we did not try before. While there can be many ways to integrate them, as an initial attempt, we tested if the sum of the Word IA (called “Sum IA”) per a particular image can work as the desired index. Below, we compare our original Image IA and Sum IA. Ideally, the index should be lower for a simple and abstract image, which would be hard to extract specific information and to report many words that are specific for that image. Also, the ideal index should be high if an image contains many distinct, clear and nameable objects. Somewhat surprisingly, we found that Image IA and Sum IA are uncorrelated (see Figure R5). But the relationship between them highly depends on the number of unique words reported under an image. In Figure R5, we display 4 examples at the extreme corners (highest/lowest Image IA/Sum IA). By looking at the top left image, we have an impression that high Sum IA (= 26.82) may be related to many words that can describe the image (e.g., rice, wheat, field, farm, yellow, brown, machine etc). However, lower Image IA (= 0.84) may be related to the fact that each word is not very specific to this image and is often reported in other images. Now, looking at the bottom right image, it may have a high Image IA (= 0.99) as it is accompanied with very specific words that are not reported in other images (e.g., boat, lake, fast, speedboat, life-vest. See Figure 4a). But as this image does not contain many objects, it may have led to smaller Sum IA (=12.82). But it is hard to say why the top right dog image was described with many (Sum IA = 28.6) specific words (Image IA = 0.95) while the wheel image at the bottom left was described with few (Sum IA = 11.7) and less specific words (Image IA = 0.84). Of course, we need to be careful in our inference because our impression here is based on the prolonged and unlimited duration of image viewing. Our IAs are based on the reports by participants who viewed them only briefly (67ms, 133ms or 266ms, masked). See Figure R5 linked here Figure R5. The relationship between Image IA and Sum IA. There is no correlation between Image IA and Sum IA, but the relationship highly depends on the number of unique words reported under an image. Each colour (dots and lines) means a number of unique words reported under an image. Four example images with their Sum IA (below the image) and Image IA (in the bracket) are also shown. We also examined other images. Sup Fig 6 and 7 ordered 420 images by their Image IA and Sum IA, respectively (https://osf.io/m7az6). For the convenience of the reviewer, in Figure R6, we show the 42 images with the highest Sum IA, the 42 images with the lowest Sum IA, and their Image IA. While our impressions above may be largely true, there are also notable exceptions. At this stage, we cannot say which of Image IA and Sum IA captures “the information one can extract” better. Each index is likely to be capturing different aspects of how people experience the scenes at a brief moment and report them in an intersubjectively consistent manner. To say more, we would need more research in the future, which we plan to do. See Figure R6 linked here Figure R6. a) 42 images with the highest Sum IA, ranked by Sum IA. The Sum IA and Image IA (in the bracket) of each image is shown under the image. b) 42 images with the lowest Sum IA, ranked by Sum IA. The Sum IA and Image IA (in the bracket) of each image is shown under the image. 7, There are very interesting results reported here. But to me the most important would be to see how the information extracted from the image (see above) or at least the IA, varies with the presentation rate. While the paper reports that IA are high even at the fastest rate (67 ms), I did not see a Figure showing the dependency on the rate. Reply: In order to increase the number of observations for each image, we calculated our Image IA (and Sum IA above) across SOA. It means we used N = 30 participants across three SOAs under each image. So the Image IA and Sum IA values above are the same for different SOAs. To address how these values depend on SOAs, we sacrificed the precision and calculated them for each SOA (where we had only N = 10 participants, Figure R7). From the figures we can see that both Sum IA and Image IA at SOA = 67ms are slightly lower than them at SOA = 133 and 267ms (ANOVA: for Image IA, F(2, 809.03) = 71.27, p < .001; for Sum IA, F(2, 836.19) = 41.67, p < .001). See Figure R7 linked here Figure R7. a) The boxplot showing Sum IA per SOA at each SOA. b) The boxplot showing Image IA per SOA at each SOA. 8, Finally, it would be quite interesting to know what the temporal limit at which the capacity to extract information from rapid displays breaks down? Reply: We agree with you that going shorter SOAs will be very interesting. We performed some preliminary experiments with shorter frame rates online. We confirmed its feasibility, but to be confident about the results, we believe that we need to intermix shorter SOAs with longer SOAs and test many participants with many images. Showing images with only shorter SOAs will be feasible to add to our data, but we expect that many participants will start setting a high threshold for reporting when there are no easy trials included (e.g., Lin & Murray 2014 Journal of Vision). Thus, to avoid such an effect, we probably need to replace our 67 ms condition with a shorter condition, while keeping 133 and 266ms conditions. To test the entire image set, this will mean that we need to run another 670 subjects to add the 33 ms (or 17ms) condition. Perhaps, we need to start its feasibility from the in-lab face to face experiment. Overall, we agree that this will be an important direction of research we plan to pursue, but given the time it would take to complete, the length and the density of the current paper, we prefer to do so in the future. Reflecting on this, we decided to add the following under “Presentation duration” in Discussion: “We performed some preliminary experiments with shorter SOAs online and confirmed its feasibility. To conduct such a study in the future, however, we recommend to confirm the results with in-lab participants to some extent. We also suggest that shorter SOA trials should be intermixed with longer SOA trials, so that participants can set an appropriate threshold for reports (Lin & Murray 2014 Journal of Vision). Such experiments will address an important question on the temporal limit of intersubjectively shared experience upon viewing rapid visual scenes.” 9, Finally, it may be interesting to discuss implications to theoretical debates such as the Overflow in Consciousness research. Reply: We agree that our paper has some implications to the theoretical debate on the overflow in consciousness research. Our paper contributes to this debate in two ways. First, is about the Sperling paradigm, which has been the central to the overflow debate. In Sperling’s paradigm (1960), participants are briefly shown an array of 12 letters in 3 rows and 4 columns. Generally, they are believed to report having an impression of seeing all letters. However, under the whole-report condition, where they are asked to report as many letters as they can, they cannot report no more than 4 individual letters accurately. However, when cued on a particular row, after the array disappears, they can report all letters accurately. Our results in Figure 4a cast doubt on this uncontested description of the results in the whole-report condition (See also Figure R6b, Supplementary Material 6 and 7 for two Sperling arrays, with both very high Image IA and Sum IA). Our participants in fact reported highly specific letters ({U, P, L, G, J} in Figure 4a) more frequently than the general impression of “letter array”, “alphabets”. This is consistent with some reviews (e.g., Haun et al., 2017; Bronfman et al. 2019), which propose that participants are actually perceiving more than previously thought. Second, our experiment opens up a possibility to extend the discussion of the overflow debate in more naturalistic situations, while most discussions so far centred around the results obtained with highly artificial stimuli. Nonetheless, our current study has implemented more like the whole-report condition of the Sperling paradigm. By extending it with a pre/post cued partial-report paradigm, we can expect that our paradigm provides a novel methodology to study the overflow debate with a large set of natural scene images. We included these points under “Future directions” in Discussion as follows: Page 14: “Finally, our paper has some implications to the theoretical debate on whether conscious experience is restricted by cognitive access or overflows such restriction (Block, 2007 BBS; Bronfman et al., 2019 Mind & Language). Previous debate on the overflow issue was almost always focused on the artificial stimulus situation introduced by Sperling (1960). Our paper contributes to this debate in two fresh ways. First, since the Sperling’s initial introduction of the paradigm, it has been almost always “assumed” that what participants see in the “whole-report” condition is just a gist, such as “seeing everything”, “alphabets”, and “letters” (Haun et al., 2017). Our empirical free-report challenges this notion. Even without any warning or expectation, participants report specific letters rather than generic gists (e.g., Figure 4a). Second, our paradigm opens up a possibility to examine the overflow issue with naturalistic stimuli. For that, we would need to develop equivalent experimental contrasts between the whole- vs. partial reports as in Sperling 1960, which is not impossible.\""
}
]
},
{
"id": "144465",
"date": "08 Aug 2022",
"name": "Qiufang Fu",
"expertise": [
"Reviewer Expertise Implicit learning",
"subliminal perception"
],
"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 combined a free-report and confidence rating to investigate how detailed information people can report after briefly seeing an image. Each image was presentation for 67, 133, or 267 ms, and followed by a dynamic masks for 300 ms. Six hundred and seventy participants attended this experiment online. A novel IA (Intersubjective Agreement) was developed to quantify how specifically the response words were used to describe the target image. The results showed that participants reported highly specific and detailed aspects of the briefly shown image, and IA is positively correlated with confidence.\nI found that the novel paradigm is very interesting and the new findings are intriguing. However, as the method is novel, the authors might need to elaborate it more on the novel index and how the procedure can measure what they aimed to measure.\nMy concerns are mainly as follows:\nFor each image, participants were asked to enter five words and reported their confidence for each word. Why were participants asked to report five words rather than one or two or three or four words? Is it possible that this manipulation led participants to give more specific information about each image as the scene gist was unique while there were various kinds of specific information? I am wondering whether there were a sequence effect of IA on the five words. For example, is it possible that the IA for the first word were less specific than that for the other words?\n\nThe authors used a wide array of natural and artificial images but did not report IAs separately for natural images and artificial images. However, the authors mentioned “the current study aims to introduce a novel methodology to investigate how detailed information participants can report after briefly seeing a natural scene image” in the abstract. Thus, it would be better to analyze IAs for natural and artificial images separately.\n\nThree SOAs were adopted in the current study. Previous studies indicated the accuracy increased with longer SOA in the forced-choice paradigms. I am wondering how the IA changed with SOA in the current study?\n\nGiven that when MTurk recruited more than 30 participants for a given block of 21 trials, the authors took the first 30 participants’ data for the subsequent analyses. There were 20 blocks, and thus the data from 600 rather than 670 participants were included. Is it right? Would you please make this more clear.\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? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "8656",
"date": "24 Aug 2022",
"name": "Zhang Chuyin",
"role": "Author Response",
"response": "Thank you for reviewing our paper and providing valuable comments! We will respond to your concerns one by one. 1, For each image, participants were asked to enter five words and reported their confidence for each word. Why were participants asked to report five words rather than one or two or three or four words? Reply: We agree that the number of response words is a key manipulation in our paradigm. To be honest, it is not easy to answer this “why” question. We imagine that the results might have been different if we asked participants to report 1, 2, 3, or 4 words. As a novel task, we had to start from somewhere. In the pilot version of the experiment, we asked participants to report up to 10 words per image. This task turned out to be difficult or tedious for many participants. Meanwhile, most participants seemed comfortable in reporting roughly up to 5 words per image (including an option of reporting random words with confidence rating of “Don’t know”). As we wanted to obtain as many words per image as possible, we settled on the five words. This information has been added as a footnote as follows: Footnote: “In a pilot task, we asked participants to report up to 10 words per image. This task turned out to be difficult or tedious for many participants. Most participants seemed to be comfortable in reporting roughly up to 5 words per image. As we wanted to obtain as many words per image as possible, we settled on the 5 words.” We believe that most aspects of the results would be replicated even if we reduce the number of words into 4, 3, 2, or 1. But, which aspects of the results stay the same or differ will be an empirical question. Having said that, repeating all experiments in this paper with the reduced report number of words will consume a lot of time and resources. Thus unless we have a specific question to address, we hope not to include this in this paper. We hope the reviewer would agree with this. 2, Is it possible that this manipulation led participants to give more specific information about each image as the scene gist was unique while there were various kinds of specific information? I am wondering whether there were a sequence effect of IA on the five words. For example, is it possible that the IA for the first word were less specific than that for the other words? Reply: Based on what we expect from the literature, we agree with the reviewer that participants may first report the scene gist, then more specific information. To test this, we directly analysed the sequence effect on Word IA as you suggested (see Figure R1a). Although Word IA are almost saturated to the maximum value of 1, we can still see Word IA tends to be slightly higher for earlier-reported words at all three SOAs with SOA = 67ms having strongest effect of the sequence (This is confirmed statistically: a negative correlation between report order and Word IA, r = -0.056, p < .001. The interaction between SOAs and report sequence is significant, p < .001). The report sequence didn’t influence confidence much even when we looked at separately for each SOA (Figure R1b). Thus, if we assume that Word IA captures something about “specific information” (we believe it is, as it is only high when the word is reported to the target image, but not to the other images), the report sequence does not matter much (even at the 5th location with SOA = 67ms, median Word IA is > 0.96). Perhaps, to see the report sequence effects clearly, we may need to use threshold level natural scenes (e.g., with SOA = 17 or 33 ms) in the future study. See Figure R1 linked here Figure R1. Report sequence effect analysis. a) The boxplot showing Word IA, grouped by report sequence and SOA. b) Confidence, grouped by report sequence and SOA. Because this finding is counter-intuitive and possibly going opposite of what has been established in the field using artificial stimuli, we checked if this result is true only for natural stimuli. Please be mindful that given we included only 8 artificial stimuli, the following analysis is limited. In particular, we checked the two Sperling letter arrays (1960). With this letter array stimuli, many researchers would agree that individual letters, such as {U, P, L, G, J} in Figure 4a, are specific responses, whereas descriptions about more generic aspects, such as alphabet, letter, are more like scene gist. Thus, focusing on these images makes it easier to check the report-sequence vs specificity hypothesis. For both types of reports, we calculated the percentage of responses at each report sequence (see Figure R2). See Figure R2 linked here Figure R2. The percentage of responses given at each report sequence for generic and specific responses. Under our experimental condition, it appears that participants tend to report specific letters first, then generic impressions later. It is interesting to note that this result was obtained despite the fact that we included the Sperling array in the midst of natural scenes, which would not let participants to expect specific letters. Having said that, due to the limited amount of the data, a chi-square test found no significant association between report sequence and the type of response, X2(4) = 6.03, p = .1966 (N = 30 participants for each of two images). Thus, this observation is quite preliminary. In summary, we infer that there is a very weak sequence effect that participants tend to report specific words first. This won’t influence our main finding that participants are able to report very specific information at a brief glance of the images. 3, The authors used a wide array of natural and artificial images but did not report IAs separately for natural images and artificial images. However, the authors mentioned “the current study aims to introduce a novel methodology to investigate how detailed information participants can report after briefly seeing a natural scene image” in the abstract. Thus, it would be better to analyze IAs for natural and artificial images separately. Reply: We agree that natural images and artificial images might show different results. However, because we had 412 natural scene images and only 8 artificial images (4 pairs), reported results reflect mostly for natural images. However, the overall trends of the results are quite similar as we summarised in Figure 7. In Figure 4a, we also analysed the Sperling’s letter arrays in particular, because they have been widely studied by previous studies. Our Figure 4a shows that the letter array has the highest Image IA (mean Word IA under an image), and almost all the responses were very specific. Having said that, we checked if the results changed after removing artificial images. We confirmed that they did not change. We added this in results as follows: Footnote: \"Because we had 412 natural scene images and only 8 artificial images (4 pairs), reported results about Word IA reflect mostly for natural images. We checked if any of the results changed significantly after removing artificial images, but they did not.\" 4, Three SOAs were adopted in the current study. Previous studies indicated the accuracy increased with longer SOA in the forced-choice paradigms. I am wondering how the IA changed with SOA in the current study? Reply: We note that in Fu et al.’s (2016) categorization task, participants’ accuracy increased from ~70% (SOA = 40ms) to ~90% (SOA = 213ms). Thus we checked to see if there is a significant relationship between SOA and Word IA, as a proxy of “accuracy” in our study (Note that Word IA should not be taken as “accuracy” in the usual sense, where experimenters define what the answer should be. Rather IA measures the agreement or similarity of experience among participants, which may or may not match with what experimenters’ expected answers). We added a Figure 6d into the paper (see Figure R3) to show this relationship more clearly. Interpretation of results for confidence = 1 (~5% of all responses) is somewhat complicated, because we explicitly asked participants to enter random words with confidence = 1 when they can’t give five words. In fact, entries such as “none” and “NA'' are often entered with confidence = 1. For SOA = 267ms, the median Word IA is around 0.5 when confidence = 1. This is consistent with an idea that participants know that their report does not reflect the image. For SOA = 67ms and 133ms, however, the median Word IA are higher than 0.5 (0.65 and 0.82, respectively), possibly reflecting fleeting impressions that participants had, which were actually shared with other participants in specific and selective ways as captured by Word IA. When confidence is higher than 1, Word IAs were nearly saturated (median > 0.95) for all SOAs. (There is a significant positive correlation between SOAs and Word IA (p < 0.001, multilevel regression), when we exclude confidence = 1). Perhaps, to see the SOA effect clearly, we may need to use threshold level natural scenes (e.g., with SOA=17 or 33 ms) in the future study. See Figure R3 linked here Figure R3 (Figure 6d). The boxplot showing Word IA, grouped by confidence and SOA. 5, Given that when MTurk recruited more than 30 participants for a given block of 21 trials, the authors took the first 30 participants’ data for the subsequent analyses. There were 20 blocks, and thus the data from 600 rather than 670 participants were included. Is it right? Would you please make this more clear. Reply: Thank you for catching this mistake. It’s correct that we analysed only 600 participants’ responses. We’ve clarified this in the revision."
}
]
}
] | 1
|
https://f1000research.com/articles/11-69
|
https://f1000research.com/articles/13-467/v1
|
09 May 24
|
{
"type": "Brief Report",
"title": "Negative perceptions of older adults and life satisfaction among community-dwelling older citizens in Japan",
"authors": [
"Yuho Shimizu",
"Kenichiro Sato",
"Susumu Ogawa",
"Daisuke Cho",
"Yoshifumi Takahashi",
"Daichi Yamashiro",
"Yan Li",
"Tomoya Takahashi",
"Keigo Hinakura",
"Ai Iizuka",
"Tomoki Furuya",
"Hiroyuki Suzuki",
"Kenichiro Sato",
"Susumu Ogawa",
"Daisuke Cho",
"Yoshifumi Takahashi",
"Daichi Yamashiro",
"Yan Li",
"Tomoya Takahashi",
"Keigo Hinakura",
"Ai Iizuka",
"Tomoki Furuya",
"Hiroyuki Suzuki"
],
"abstract": "Background With the rapid aging of the population, increasing life satisfaction among older adults is essential. Negative perceptions of older adults are internalized, leading to poor mental health. This study hypothesized that participants with more negative perceptions of older adults would have lower life satisfaction.\n\nMethods A cross-sectional survey of older adults was conducted across five wards and four cities in Tokyo, Japan. Participants responded to questions regarding demographics, life satisfaction, and negative perceptions of older adults. Data from 285 participants (264 women, M = 71.97 years) were analyzed.\n\nResults The intraclass correlation coefficient for life satisfaction concerning residential areas was. 03 (95% confidence interval [CI] = [-.03, .10]). Instead of multilevel models, a multiple regression model with life satisfaction as the dependent variable and negative perceptions of older adults and demographics as the independent variables yielded the best fit. Results indicated that participants with more negative perceptions of older adults reported lower life satisfaction (β = -.16, 95% CI = [-.28, -.04], p = .008), supporting our hypothesis.\n\nConclusions This study was constrained by limited variance in residential areas and a predominantly female participant pool. Previous studies have shown that higher life satisfaction is associated with increased social participation and extended life expectancy, and interventions aimed at enhancing life satisfaction in older adults are significant. Further exploration is warranted to ascertain whether a causal relationship exists, wherein more negative perceptions of older adults diminish life satisfaction.",
"keywords": [
"Psychological Well-Being",
"Quality of Life",
"Stereotyping",
"Life Satisfaction",
"Multilevel Models"
],
"content": "Introduction\n\nGlobally, the population is aging rapidly. This is especially evident in Japan, where 29.0% of the population will be 65 years or older by 2022.1 While social problems associated with aging have become more apparent, older adults generally have a higher level of life satisfaction than other generations.2,3 However, life satisfaction among older adults in Japan has declined in recent years.4 As life satisfaction among older people is closely associated with a higher level of physical health,5 increased social participation,6 and longer life expectancy,7,8 efforts to increase life satisfaction in this demographic are of great importance.\n\nOne variable that could be related to life satisfaction among them is negative perceptions of older adults, which is how older citizens perceive the social group of “older adults.” Stereotype embodiment theory (SET) assumes that older adults internalize negative old-age perceptions.9 Moreover, the SET argues that older adults who hold more negative perceptions are more likely to experience various negative effects. Previous studies have shown that older adults with more negative perceptions have poorer mental health,10,11 lower cognitive function,12 and slower recovery from illness.13 Similar to the SET, the risks of ageism model14 suggest that three factors broadly inhibit active aging: “stereotype embodiment,” “stereotype threat,” and “being a target of ageism.” Based on the above findings, negative perceptions of older adults among the older participants will be associated with lower life satisfaction.\n\nWe conducted a cross-sectional survey of community-dwelling older adults in Japan and examined the relationship between their negative perceptions and life satisfaction. Participants were enrolled in a health course conducted by local governments in Tokyo, Japan to train volunteers to read picture books to their children. In addition to population and economic size, each area had different main goals for the health course presented when recruiting participants (e.g., volunteer training and/or dementia prevention). Thus, an exploratory multilevel analysis was conducted to examine the relationship between the two variables, considering the effect of participants’ residential areas. We hypothesized that participants with more negative perceptions of older adults would have lower levels of life satisfaction.\n\n\nMethods\n\nA power analysis assuming a small to moderate effect size (ρ = .20, α = .05, 1–β = .80) yielded a required sample size of 193. Three hundred and two older Japanese individuals from Tokyo participated in this study. However, 17 participants were excluded from the analysis because they were < 65 years old. Thus, the data of 285 participants (aged 65–92, M = 71.97 years, SD = 5.16) were analyzed. The participants comprised 21 men and 264 women. They were older adults who voluntarily applied for a health course to train volunteers to read picture books to children, which was held in five wards and four cities in Tokyo from 2021–2022. A summary of the participants by residential area is available in the Open Science Framework (OSF) repository (https://doi.org/10.17605/OSF.IO/X6JSN).15 Participants were required to attend the health course venue independently. Note that the data for this study were collected before the implementation of the health course; therefore, our results do not include course effects. This study was approved by the first author’s institution for ethical review.\n\nAll procedures were in accordance with the ethical standards of Tokyo Metropolitan Institute for Geriatrics and Gerontology (approval number: 748; June 10, 2020) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants in written format.\n\nNegative perceptions of older adults were measured using the eight adjectives (five-point Likert scale).16 Participants were asked the following question: “To what extent do you think older adults fit each of the following adjectives?” Adjectives presented to participants included “depressed” and “passive.” The mean was taken as the score (α = .89), with higher scores indicating more negative perceptions of older adults.\n\nLife satisfaction was measured using the five-items of the Satisfaction with Life Scale17 measured on a seven-point Likert scale. Examples of items include: “In most ways, my life is close to my ideal.” The mean was taken as the score (α = .86), with higher scores indicating a higher level of life satisfaction. Demographic variables included years of education, age, and sex.\n\nParticipants received an explanation regarding the use of survey data for research purposes and agreed to participate in the study. Subsequently, they responded to demographic variables, life satisfaction, and negative perceptions of older adults. The statistical software R (ver.4.1.0) was used for all analyses. The list of questions, data used in the analysis, scripts for R, histograms for each variable, and summary statistics can be accessed through the OSF.\n\n\nResults\n\nThe intraclass correlation coefficient (ICC) for life satisfaction concerning residential areas was.03 (95% CI = [-.03, .10]). Therefore, applying a multilevel analysis was not necessary. However, in this study, we conducted a simple multiple regression analysis (Model 1), a random effect with an analysis of covariance (RANCOVA) model, including the effect of residential area (Model 2), a random intercept and slope model with a group-level effect of negative perceptions of older adults (Model 3), and a random intercept and slope model with a cross-level interaction (Model 4). These models were compared in Table 1.\n\n** p < .01.\n\nLife satisfaction was used as the dependent variable in each analysis. In Model 1, a multiple regression analysis including the demographics (years of education, age, and sex) showed that participants with more negative perceptions of older adults had lower life satisfaction (β = -.16, 95% CI = [-.28, -.04], p = .008). In Model 2, we conducted a RANCOVA model with an individual-level effect (group-mean centering) of negative perceptions of older adults and found a similar effect to Model 1 (β = -.18, 95% CI = [-.30, -.05], p = .005). In Model 3, we employed a random intercept and slope model, including a group-level effect (deviating from regional means) of the negative perceptions of older adults. The results showed that the individual-level effect (β = -.16, 95% CI = [-.33, .02], p = .11) and the group-level effect (β = -.07, 95% CI = [-.58, .42], p = .80) were not significant. In Model 4, we employed a random intercept and slope model, including cross-level interaction. The results showed that the individual-level effect (β = -.15, 95% CI = [-.33, .04], p = .18), the group-level effect (β = -.08, 95% CI = [-.66, .44], p = .77), and the cross-level interaction (β = .02, 95% CI = [-.14, .18], p = .85) were not significant.\n\nModel comparisons were conducted using the Akaike’s information criterion and the Bayesian information criterion, and Model 1 was determined to fit the data best. Note that when participants aged under 70 (n = 103) and 70 or over (n = 182) were analyzed separately; the results for both groups were similar to those in the main manuscript (see OSF). Similar results were obtained in a multiple regression analysis using a dummy variable for the residential area, with zero for the ward and one for the city (see OSF). Thus, our hypothesis that participants with more negative perceptions of older adults have lower levels of life satisfaction was supported.\n\n\nDiscussion\n\nIn this study, we conducted a cross-sectional survey of community-dwelling older adults in nine areas in Tokyo to examine the relationship between negative perceptions of older adults and life satisfaction. Each multilevel model fits the data worse than the simple multiple regression analysis. The results showed that participants with more negative perceptions of older adults had lower life satisfaction, thus supporting our hypothesis. Note that a reverse relationship could also be assumed: individuals with lower life satisfaction have more negative perceptions of older adults. The same association was found when this possibility was examined, as in the main manuscript (see OSF).\n\nIn this study, the ICC for life satisfaction in residential areas was small, and the fit of each multilevel model was relatively low. One reason for this may be that our participants were limited to those in a health course, training volunteers to read picture books. While detailed motivations for participating in the course varied from individual to individual, the attitude of “I am interested in picture books” and “I want to work as a volunteer” was probably shared by almost all participants. Thus, possibly, the group-level effect was relatively small due to the presence of factors common to participants across residential areas.\n\nAs this study is a cross-sectional survey, we should examine whether a causal relationship exists between more negative perceptions of older adults and decreased life satisfaction. Meanwhile, given that older adults with negative perceptions of themselves have poorer mental health,10,11 positively changing their perceptions of older adults is important. One way to achieve this is to present people with information that contradicts negative old-age stereotypes. For example, negative stereotypes exist that “older adults are prone to illness,” but it was shown that presenting people with the content that “many older adults are healthy enough and able to live on their own” decreased ageism toward older adults.18,19 Although these findings targeted younger people, a similar experimental manipulation for older adults may affirm their perceptions of older adults. Future empirical studies are required to positively change the perceptions of old age among older adults.\n\nThis study had two major limitations. First, the areas covered in this study were all located in Tokyo, Japan, and the regional differences were small. Compared with Japan’s underpopulated regions, all nine regions in this study share a high population density and a very small number of people engaged in agriculture, forestry, and fisheries. Therefore, follow-up studies are required to select regions with significantly different geopolitical characteristics from a wide range of prefectures. Second, the participation was skewed toward women. Since this study was conducted before a health course to train volunteers to read picture books to children, women comprised the majority of the participants. Note that results similar to those in the main manuscript were obtained when the analysis was limited to women’s data (see OSF); however, this study could not make adequate comparisons between men and women. Therefore, our findings should be re-examined with a sufficient number of male participants.\n\nIn this study, we found an association between negative perceptions of older adults and life satisfaction among community-dwelling older adults. Interventions that increase life satisfaction in older adults are meaningful because higher life satisfaction leads to increased social participation and longer life expectancies. Thus, it would be useful to focus on the negative perceptions of older adults. In addition, we conducted an exploratory multilevel analysis. Future studies on life satisfaction and negative perceptions of older adults in a broader geographic area should consider the effects of residential areas.\n\nAll procedures were in accordance with the ethical standards of the research committee of Tokyo Metropolitan Institute for Geriatrics and Gerontology, (approval number: 748; June 10, 2020 and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written Informed consent was obtained from all individual participants included in the study.",
"appendix": "Data availability\n\nThe data used in the analysis is available in the Open Science Framework (OSF) repository:\n\nNegative perceptions of older adults and life satisfaction among community-dwelling older citizens in Japan, https://doi.org/10.17605/OSF.IO/X6JSN. 15\n\nThe project contains the following data:\n\n• old image place4.csv (dataset),\n\n• old image place code_3.R (the R codes for analysis),\n\n• OSF_supplemental_1.pdf (supplementary file of the manuscript).\n\nThis data was collected and formed by the authors of this paper. The license of this data is CC-BY 4.0 International.\n\n\nAcknowledgements\n\nThe authors acknowledge the continued efforts in the management of survey by Senior Citizen Activities Promotion Section in Welfare Division of Hachioji City in Tokyo, Japan. The authors also thank members of the Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute for Geriatrics and Gerontology.\n\n\nReferences\n\nJapan Cabinet Office: White paper on aging society in 2023. Accessed 2 March, 2024. Reference Source\n\nBlanchflower DG, Oswald AJ: Is well-being U-shaped over the life cycle? Soc. Sci. Med. 2008; 66: 1733–1749. PubMed Abstract | Publisher Full Text\n\nKurokawa H, Ohtake F: Age and cohort effects on happiness, satisfaction, and stress. J. Behav. Econ. Financ. 2013; 6: 1–36. Publisher Full Text\n\nJapan Cabinet Office: White paper on aging society in 2021. Accessed 2 March, 2024. Reference Source\n\nKim ES, Delaney SW, Tay L, et al.: Life satisfaction and subsequent physical, behavioral, and psychosocial health in older adults. Milbank Q. 2021; 99: 209–239. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaeriswyl M, Oris M: Social participation and life satisfaction among older adults: Diversity of practices and social inequality in Switzerland. Ageing Soc. 2023; 43: 1259–1283. Publisher Full Text\n\nDiener ED, Chan MY: Happy people live longer: Subjective well-being contributes to health and longevity. Appl. Psychol.: Health Well-Being. 2011; 3: 1–43. Publisher Full Text\n\nDiener ED, Ryan K: Subjective well-being: A general overview. S. Afr. J. Psychol. 2009; 39: 391–406. Publisher Full Text\n\nLevy BR: Stereotype embodiment: A psychosocial approach to aging. Curr. Dir. Psychol. Sci. 2009; 18: 332–336. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWerner P, Stein-Shvachman I, Heinik J: Perceptions of self-stigma and its correlates among older adults with depression: A preliminary study. Int. Psychogeriatr. 2009; 21: 1180–1189. PubMed Abstract | Publisher Full Text\n\nWettstein M, Wahl HW, Siebert JS: 20-year trajectories of health in midlife and old age: Contrasting the impact of personality and attitudes toward own aging. Psychol. Aging. 2020; 35: 910–924. PubMed Abstract | Publisher Full Text\n\nSiebert JS, Braun T, Wahl HW: Change in attitudes toward aging: Cognitive complaints matter more than objective performance. Psychol. Aging. 2020; 35: 357–368. PubMed Abstract | Publisher Full Text\n\nLevy BR, Slade MD, May J, et al.: Physical recovery after acute myocardial infarction: Positive age self-stereotypes as a resource. Int. J. Aging Hum. Dev. 2006; 62: 285–301. PubMed Abstract | Publisher Full Text\n\nSwift JH, Abrams D, Lamont RA, et al.: The risks of ageism model: How ageism and negative attitudes toward age can be a barrier to active aging. Soc. Issues Policy Rev. 2017; 11: 195–231. Publisher Full Text\n\nShimizu Y: Negative perceptions of older adults and life satisfaction among community-dwelling older citizens in Japan. [Dataset]. OSF. 2024. Publisher Full Text\n\nToyoshima A, Tabuchi M, Sato S: Relationship between recognition of elder abuse and attitude toward elderly people among young adults. Japanese J. Gerontol. 2016; 38: 308–318. Publisher Full Text\n\nDiener ED, Emmons RA, Larsen RJ, et al.: The satisfaction with life scale. J. Pers. Assess. 1985; 49: 71–75. Publisher Full Text\n\nLytle A, Levy SR: Reducing ageism: Education about aging and extended contact with older adults. Gerontologist. 2019; 59: 580–588. PubMed Abstract | Publisher Full Text\n\nShimizu Y, Suzuki M, Hata Y, et al.: Older adults are healthier than many people expect: Reducing anti-old attitudes. Educ. Gerontol. 2023; 49: 1116–1127. Publisher Full Text"
}
|
[
{
"id": "297565",
"date": "05 Jul 2024",
"name": "Anna Zalewska",
"expertise": [
"Reviewer Expertise health sciences"
],
"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 paper. This is a timely issue to explore. It is mostly clear paper, there is, however, issues that must be resolved before the study can be accepted for indexing. Several comments and suggestions for the authors. - In the abstract, instead of a hypothesis, the authors should state the aim. - In the abstract, authors should not describe limitations in their conclusions. - In the abstract, authors should not refer to other studies in their conclusions, but present a conclusion from their own research. - The introduction does not exhaust the topic. - There is no clearly defined aim of the study. - The last part of the introduction regarding the organization of research should not be included in it (it is part of the material and methods subsection). - Lack of clear inclusion and exclusion criteria. - The results lack an all-encompassing table, a flowchart for the selection of patients included with the step-by-step reasons for exclusion. - Can the authors provide the Cronbach’s alpha value for scales used? - In addition to the limitations, it is also worth describing the strengths of the study. - Research articles usually do not use the word „we”, „our” and regularly use passive verbs.\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? 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? Partly",
"responses": [
{
"c_id": "12026",
"date": "23 Aug 2024",
"name": "Yuho Shimizu",
"role": "Author Response",
"response": "Reply to Reviewer 1 We express our appreciation to the reviewer for their insightful comments on our manuscript, which have helped us significantly improve the paper. Additionally, we have revised our manuscript according to the reviewer’s comments. Please find below our point-by-point responses to the comments. In the abstract, instead of a hypothesis, the authors should state the aim. In the abstract, authors should not describe limitations in their conclusions. In the abstract, authors should not refer to other studies in their conclusions, but present a conclusion from their own research. We appreciate the reviewer’s comments. Along with the reviewer’s comments, we have revised the Abstract. The introduction does not exhaust the topic. There is no clearly defined aim of the study. We thank the reviewer’s helpful comment regarding this point. We have added the following statement to the third paragraph of Introduction: “This study’s aim is examining the relationship between their negative perceptions toward older adults and life satisfaction.” The last part of the introduction Regarding the organization of research should not be included in it (it is part of the material and methods subsection). We thank the reviewer’s helpful comment regarding this point. We have added the following statement to the first paragraph of Methods: “In addition to population and economic size, each area had different main goals for the health course presented when recruiting participants (e.g., volunteer training and/or dementia prevention). Thus, an exploratory multilevel analysis was conducted to examine the hypothesis, considering the effect of participants’ residential areas.” Lack of clear inclusion and exclusion criteria. The results lack an all-encompassing table, a flowchart for the selection of patients included with the step-by-step reasons for exclusion. We thank the reviewer for this suggestion. In this study, participants were older adults who voluntarily applied for a health course to train volunteers to read picture books to children. There were no other exclusion criteria specifically, as long as the participants met the criteria of being 65 years of age or older. Therefore, we have determined that the flowchart regarding participant exclusions is unnecessary. Accordingly, we have added the following statement to the first paragraph of Methods: “Participants were required to attend the health course venue independently. There were no other exclusion criteria specifically, as long as the participants met the criteria of being 65 years of age or older.” Can the authors provide the Cronbach’s alpha value for scales used? We thank the reviewer for this suggestion. We have added the Cronbach’ alpha for each scale. In addition to the limitations, it is also worth describing the strengths of the study. We thank the reviewer’s helpful comment regarding this point. We have added the following statement to the last paragraph of Discussion: “The strength of this study is that the analysis of the relationship between negative perceptions toward older adults and life satisfaction takes into account the effects of residential areas. Future studies on life satisfaction and negative perceptions toward older adults in a broader geographic area should consider regional effects.” Research articles usually do not use the word “we”, “our” and regularly use passive verbs. We thank the reviewer for this point. The text has been corrected to a form that does not use “we” or “our.” We have submitted the revised version of the manuscript. We look forward to hearing from you regarding our revised manuscript and would happily respond to any further questions and comments you may have."
}
]
},
{
"id": "297567",
"date": "16 Jul 2024",
"name": "Susiana Nugraha",
"expertise": [
"Reviewer Expertise Gerontology and 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\nThis paper discusses about the negative perception of being older adult is associated with life satisfaction. The title of this paper is little bit biased in wording. the term of \"negative perception of older adult\" tend to created ambiguous meaning for reader. I suggest you to add some sentence to avoid any ambiguity.\nThe introduction part does not clearly highlight the important of this study, as well as the state of art of this study has not well described.\nThe method section does not clearly explain the instrument being used and its measurement techniques. The role of other confounding variable might necessary to identify. I would like to see some discussion of the finding of the papers in relation to recent findings and development in active ageing program in Tokyo. The conclusion should concisely mention the finding as well as the implication of the study to the program and policy development.\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? 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? No",
"responses": [
{
"c_id": "12027",
"date": "23 Aug 2024",
"name": "Yuho Shimizu",
"role": "Author Response",
"response": "Reply to Reviewer 2 We express our appreciation to the reviewer for their insightful comments on our manuscript, which have helped us significantly improve the paper. Additionally, we have revised our manuscript according to the reviewer’s comments. Please find below our point-by-point responses to the comments. The title of this paper is little bit biased in wording. the term of “negative perception of older adults” tend to created ambiguous meaning for reader. I suggest you to add some sentence to avoid any ambiguity. We thank the reviewer for this point. We have revised the title of our paper. The introduction part does not clearly highlight the important of this study, as well as the state of art of this study has not well described. We sincerely thank the reviewer for this point. We have added the study’s aim and strength to the third paragraph of Introduction: “This study’s aim is examining the relationship between their negative perceptions toward older adults and life satisfaction. In this study, a cross-sectional survey of community-dwelling older adults in Tokyo, Japan, was conducted. The hypothesis is that participants with more negative perceptions toward older adults would have lower levels of life satisfaction. The study will also focus on the effect of the participant's residential area, details of which are provided in the next section, along with information about the participant.” The method section does not clearly explain the instrument being used and its measurement techniques. The role of other confounding variable might necessary to identify. We thank the reviewer’s helpful comment regarding this point. We have added the following statement to the first paragraph of Participants section of Methods: “A paper-based questionnaire survey was used in this study. Participants read the questionnaire themselves and responded using a writing instrument.” We have also added the following statement to the second paragraph of Measurements section of Methods: “Although there may be other confounding individual difference variables, other variables were not measured in this study in consideration of participants’ burden.” I would like to see some discussion of the finding of the papers in relation to recent findings and development in active ageing program in Tokyo. The conclusion should concisely mention the finding as well as the implication of the study to the program and policy development. We thank the reviewer’s helpful comment regarding this point. We have added the following statemen to the fourth paragraph of Discussion: “In this study, a cross-sectional survey of community-dwelling older adults who voluntarily applied for a health course to train volunteers to read picture books to children in Tokyo was conducted. The findings of this study can be utilized to improve programs aimed at promoting the health of older adults. For example, reducing negative perceptions toward older adults prior to enrolling in a program may make it easier for them to achieve greater life satisfaction. As noted above, this study is limited to the examination of correlations, and longitudinal experiments should be conducted in the future.” We have submitted the revised version of the manuscript. We look forward to hearing from you regarding our revised manuscript and would happily respond to any further questions and comments you may have."
}
]
}
] | 1
|
https://f1000research.com/articles/13-467
|
https://f1000research.com/articles/13-440/v1
|
02 May 24
|
{
"type": "Systematic Review",
"title": "Systematic review of COVID-19 vaccine acceptance and hesitancy: global perspectives and implications.",
"authors": [
"Muhammad Mohsin khan",
"Noman Shah",
"Mhran Daie",
"Noman Shah",
"Mhran Daie"
],
"abstract": "The acceptance rate towards COVID-19 vaccination among the global population could be higher due to the need for more education or awareness of prevention strategies to control the COVID-19 outbreak. Thus, there is a dire need to reduce the population’s reluctance towards COVID-19 vaccination across the globe, which will ultimately lead to the implementation of prevention and control strategies against the COVID-19 virus and improving health outcomes across the globe. The following study intends to conduct a systematic review of the literature to evaluate the relationship between COVID-19 vaccination and the current trends related to COVID-19 vaccination faced by the global population. The methodology employed in this study primarily focused on assessing secondary data by conducting a systematic literature review. Internet and electronic databases were used to select research articles to obtain secondary sources. Six articles were selected from ScienceDirect and Google Scholar for a systematic literature review. The keywords used for the selection of articles were “COVID-19,” “Global trends,” Reluctance, “and “vaccination.” The selected articles that were most suitable for the topic consisted of global trends related to COVID-19 vaccination. Six articles relevant to the topic were selected and reviewed. The selected articles showed data collection results from different research journals. The findings of the six research articles depicted common themes, such as each vaccine having a different level of access attitude towards the regional existence, which primarily depends on the variability to determine the vaccine’s effectiveness. Further studies are required to evaluate the factors and strategies that help healthcare organizations and governments reduce the reluctance to use the COVID-19 vaccine among populations worldwide.",
"keywords": [
"COVID-19",
"Global trends",
"Reluctance",
"vaccination."
],
"content": "Introduction\n\nCOVID-19 is a virus belonging to the family Corona viridae. They can affect both humans and animals. According to Caserotti et al., COVID-19 is a severe acute respiratory syndrome caused by a novel virus. It can lead to several respiratory outcomes and cause mild infections such as a common cold. Coronavirus originated among humans in Wuhan, China, in 2019, and later spread across the globe. In addition, Fung et al. stated that the COVID-19 outbreak has severely affected several countries worldwide.6,8 In 2020, the World Health Organization (WHO) declared COVID-19 as a global pandemic. During that year, 66 regions outside China reported 8,568 confirmed cases, with Italy and Iran having a higher prevalence. In 2020, the total number of confirmed COVID-19 cases worldwide reached 118,638,190, resulting in 2,632,074 deaths. The United States had the highest rate of confirmed COVID-19 cases, followed by Brazil and India as the second- and third-highest regions, respectively. Hanney et al. reported that in 2020, the UK had the sixth highest prevalence of COVID-19, with over 306,000 cases and 43,000 deaths.9 According to WHO, as of now, there have been 550,218,992 reported cases of COVID-19 worldwide, with 6,343,783 reported deaths due to the infection. The current statistics of COVID-19 by region are shown in below mentioned Figure 1.\n\nSource: Ref. 22.\n\nThe above graph indicates that the prevalence of COVID-19 is at its peak in Europe and America. The WHO further reported that 12 037, 259, and 035 vaccines will be administered in 2022 to reduce the global prevalence of COVID-19. The graph below shows that 62.2% of people had received at least one dose of the COVID-19 vaccine. Notably, 57.8% of the population has received two or three doses of the COVID-19 vaccine. To date, 12.13 billion vaccine doses have been administered worldwide. On average, approximately 5.51 million vaccine doses are administered daily.\n\nThe current trends of protection against COVID-19 emphasize that over 7.81 billion people have been administered the vaccine dose.14 However, Zhao et al. stated that the acceptance rate towards COVID-19 vaccination in developing countries such as Nigeria needs to be higher because of a lack of education or awareness of prevention strategies to control the COVID-19 outbreak.24,25 A high acceptance rate among the population is necessary to improve the administration rate of the COVID-19 vaccine.14 Thus, there is a dire need to reduce the population’s reluctance to receive COVID-19 vaccination worldwide, which will ultimately lead to prevention and control strategies against COVID-19 and improve health outcomes across the globe.\n\nSource: Ref. 15.\n\nAccording to Al-Amer et al., organizations and governments worldwide have made vaccination for COVID-19 mandatory to enhance the vaccination rate.4 Governments and institutions have implemented several policies to make COVID-19 vaccination mandatory. For example, proof of at least one or two doses of vaccination is mandatory for working in specific roles and settings, or attending school. An employee cannot receive his/her salary without administering one or two doses of COVID-19 vaccines, and a student cannot sit in the classroom without administering vaccination globally. These policies are ethically justified as they protect the health and well-being of the population. However, policies may pose issues for individual autonomy, liberty, and other adverse effects. These issues have made the vaccination of COVID-19 unsuccessful to some extent and caused reluctance among people towards COVID-19 vaccination worldwide. In this regard, the following study proposes to conduct a comprehensive literature review to evaluate the resistance to COVID-19 vaccination and explain the current trends related to COVID-19 immunization experienced by the global population.\n\n\nAim and objectives\n\nThe main aim of this study was to evaluate reluctance to vaccinate against COVID-19 worldwide. This study primarily focused on the current global perspective of COVID-19 prevention. This study established a series of goals.\n\n• To explore the current trends associated with COVID-19 vaccination faced globally Population.\n\n• To evaluate the factors and barriers that occur in the acceptance of COVID-19 vaccination.\n\n• To explore the rate of reluctance to vaccinate COVID-19 among populations worldwide.\n\nThe research question formulated to be addressed through this systemic literature review is\n\n• What is the reluctance to vaccinate against COVID-19 and explain the current barriers related to COVID-19 vaccination faced by the global population?\n\n\nMethods\n\nThe research approach adopted by the study involved conducting an extensive review of the secondary data and thoroughly examining the relevant literature. Internet and electronic databases were used to select research articles to obtain secondary sources. Six articles were chosen from ScienceDirect, Google Scholar, and PubMed to conduct a systematic literature review. The keywords used for the selection of articles were “COVID-19,” “Global trends,” Reluctance, “and “vaccination.” The selected articles that were most suitable for the topic consisted of global trends related to COVID-19 vaccination.\n\nThe study utilized inclusion and exclusion criteria to sift through relevant data. Articles that served as determinants of COVID-19 vaccines were included in the research. It is essential that the study encompasses articles that are performed and surveyed globally and written in English. This study focuses solely on articles that can be published as research articles. Articles published before the COVID-19 pandemic were not included in the study. Additionally, articles that provided survey information on particular groups, such as healthcare workers or students, were not considered in this study.\n\nThe reporting items for systemic literature review usually identified the PRISMA flowchart, as it provides evidence-based items for results synthesis.17 The PRISMA flowchart highlights the number of relevant literature reviews eligible to provide significant information related to the research question. The flowchart also includes the excluded articles and duplicate literature reviews.\n\nThe flow chart (Figure 3) above shows that the PRISMA flowchart helped retrieve studies from the databases after putting keywords on each database. After removing duplicates and screening the articles based on the abstract and availability of full-text articles, seven articles were selected and reviewed.\n\nA thematic analysis technique was used to analyse the findings of the selected articles following a systematic review. This technique enabled the researcher to determine patterns and themes in the findings of studies on people’s reluctance to vaccinate COVID-19 worldwide.\n\nA review of previous studies was conducted to evaluate the rate of reluctance to vaccinate COVID-19 among populations across the world. Thematic analysis was used to present the findings of this systematic literature review, and each article was reviewed under the following themes:\n\nSallam stated that the term vaccine reluctance reflects a delay in the vaccination acceptance rate.20 The refusal rate of vaccination is likely to affect the rate of vaccine administration among the entire population. Some factors that influence the reluctance to accept vaccination include changing people’s attitudes towards the availability of vaccine services. These factors included complacency, suitability, and motivation. Complacency refers to a decreased perception of disease risk; hence, vaccination appears unnecessary. The term confidence denotes the belief in the vaccination approach, which includes safety, effectiveness, and all perspectives of healthcare organizations. The term suitability entails affordability, availability, and delivery in the context of comfort.\n\nOther complexities affecting COVID-19 vaccination reluctance were analysed using a triad of epidemiologically related environments, mediators, and human factors. These factors include the environment, public health policies, socioeconomic factors, and reports circulated through social media.20 Other disease-related factors involve the perception of vaccines that consist of the rate of efficacy, efficiency, and, most importantly, safety. Human factors depend on information, past experience, education, and income levels.\n\nAccording to Kabir et al., COVID-19 has caused 1.7 million deaths and 80 million cases worldwide in 2020.10 The research team and pharmaceutical companies have contributed significantly to the formulation of effective and safe vaccines against COVID-19. Preventive actions have been implemented to stop the transmission of COVID-19 between individuals. Although efforts to establish a vaccine have resulted in massive success for COVID-19 vaccination, several significant hindrances can stimulate reluctance regarding the availability of COVID-19 vaccination.12\n\nThe major challenge in implementing COVID-19 vaccination is the unfair distribution and long-term efficacy of vaccination worldwide. Another significant challenge is to control efforts to reduce the negative consequences of COVID-19 vaccines in specific countries. The access rate of the COVID-19 vaccine relies mainly on the immunity rate of the population to control the spread of pathogens, depending on the reproductive number of infectious diseases. The range of immunity observed in individuals is approximately 60-70% for mandatory virus transmission.23 A high rate of immunity is required for the vaccine to be effective in protecting human factors and achieving the goal of reducing the COVID-19 effect.\n\nAccording to Adu et al., the rate of COVID-19 vaccination tends to be higher in low- and middle-income countries, with 4.98 billion people receiving one dose of the COVID-19 vaccine globally in 2022.3 Healthcare practitioners and organizations have reported that high administration and acceptance of effective vaccines are required to substantially reduce the COVID-19 outbreak. It is estimated that the vaccine needs an efficacy of approximately 95-85%, along with a population range from 63-75%, to get protected to achieve herd immunity against the pandemic infection. Recently, there have been potential implications of attitudes identified from COVID-19 vaccination that have been increasing over time, representing the positive movement of the population towards vaccination. The study also revealed the religious affiliation predicted from COVID-19 vaccination, mainly in Jordan, Somalia, Malaysia, and Ethiopia, including common demographic factors.3 Demographic factors are mainly linked to the vaccination uptake of COVID-19, including sex, differences in marital status, level of education, residence area, and various affiliations of religion that cause refusal of COVID-19 vaccines.\n\nMoreover, Abu-Odah, Su, and Musa conducted a descriptive qualitative study to evaluate the unwillingness of individuals to be vaccinated against the COVID-19 vaccine and determine suggestions to enhance the vaccination level in Palestine.2 The results of the study demonstrated that the unwillingness of people in Palestine to get vaccinated against the COVID-19 vaccine was due to several factors, such as the spread of invalid rumours, conspiracy theories, misinformation that they received regarding the vaccine, their side effects on social media, and doubts towards vaccines purchased by the government. There is a pressing need to develop motivational techniques, including monetary rewards, to encourage individuals to receive the COVID-19 vaccine. Implementing these strategies can motivate individuals to be vaccinated.\n\nFurthermore, approximately 63% of the global population received only one dose of the COVID-19 vaccine by 2022.16 Around 10.94 billion doses are estimated to not reach the global population. Rural areas and countries have lower vaccination rates than those in urban areas. Their ages largely determine the percentage of fully vaccinated individuals. International agencies such as the European Medicines Agency have authorized four vaccines. These vaccines consisted of two DNA-based vaccines (ChAdOx1 nCov-19 and Ad26.COV2.S) and two mRNA-based vaccines (BNT162b2 and mRNA-1273). Administering vaccines is highly correlated with decreasing SARS-COV-2 death rates.13 Although the COVID-19 vaccine has proven to be effective, it has been associated with adverse side effects such as thrombocytopenia, thrombosis, and haemorrhage. These outcomes have caused some individuals to be hesitant to receive the COVID-19 vaccine during the COVID-19 outbreak. Approximately 5% of people in the United States reported experiencing allergic reactions and other side effects. In Europe, over 7.2 million people hesitate to be vaccinated against COVID-19 and need assurance about its safety.18 Additionally, these populations include a large ratio of unwilling adults based on the causes of covariates, such as sociodemographic factors.\n\nDemonstrations have proven that the COVID-19 vaccine has been created to hinder or diminish the spread of COVID-19 on a global scale.20 No treatment has been discovered specifically for the COVID-19 pandemic, and the implication of the vaccine is necessary for the population. However, a study by Million et al. evaluated that the acceptance of vaccination for COVID-19 can be influenced by the vaccine’s safety, efficacy rate, causes of adverse effects, belief in the government’s authority, and religious beliefs, which are the primary factors that inhibit the uptake rate of the COVID-19 vaccine.12 The COVID-19 vaccine, which is designed to prevent or mitigate the spread of the COVID-19 infection worldwide, has only been received by 28.3% of the population in low-income countries.20 This means that the benefits of the COVID-19 vaccine have not yet been fully realized on a global scale. Moreover, Adu et al. demonstrated the benefits perceived from vaccination and indicated that vaccine acceptance rate improvement could decrease the outbreak of the COVID-19 pandemic.3\n\nResearch findings indicated that many senior citizens received complete vaccination, including booster shots.16 The data from early surveys of lower-middle and high-income brackets show that the number of vaccine doses administered to high-income and upper-middle individuals is significantly higher than that administered to low-income individuals. The other factors that cause disinclination to vaccinate against COVID-19 are the effective cost, vaccination schedules, and, most importantly, reliability decisions for vaccine uptake. The findings of these studies are related to the results of the Yoneoka et al. study, which showed that the acceptance rate of COVID-19 vaccination was low in Africa due to a low rate of poverty and lack of knowledge about the effectiveness and potency of COVID-19 vaccines against the COVID-19 outbreak.23\n\nA large proportion of adults are estimated to be unwilling to participate in vaccination due to socio-demographic factors.18 The challenges faced against the uptake of COVID-19 in Europe were mainly due to women’s low educational levels. Compared to European countries, the acceptance rate of the COVID-19 vaccine was higher in the UK and Canada during the pandemic.18 Middle Eastern countries also showed lower acceptance rates, and Russia reported a lower acceptance rate in terms of safety and efficacy issues. However, the major challenge of COVID-19 vaccination was to control the negative consequences caused by the vaccination of COVID-19. A sufficient level of immunity is necessary to achieve the desired range of vaccine effectiveness, which in turn can help mitigate the impact of COVID-19 on human health. Cases of anaphylaxis with several types of allergic reactions occur mainly after vaccination.13 This study examined a particular factor: apprehension related to needles or blood. This factor has been recognized as a source of anxiety in smaller communities. These are also related to population safety concerns as vaccines can induce allergic reactions. These factors might make people more resistant to COVID-19 vaccination worldwide.\n\nThe Table 1 below shows the findings of each article in this systematic literature review. The table contains the author’s name, study design, aim, and study outcomes.\n\n\nDiscussion\n\nThe findings of this systematic literature review showed that a high rate of reluctance towards vaccinate for COVID-19 resulted in an increased mortality rate. The COVID-19 vaccine has the potential to decrease the mortality rate caused by infection. The dose of the COVID-19 vaccine helps decrease severe symptoms of the disease and the death rate worldwide. The study also showed that several vaccines were developed for treating COVID-19 based on DNA and RNA. However, many of them need to be more effective against infection due to access to different regional variants. Each vaccine has a different acceptance rate and depends on population variability. Several pharmaceutical companies have contributed significantly to the generation of safe and effective vaccines against the COVID-19 pandemic. The factors required to increase the availability of vaccine services are competency, feasibility, and affordability. Most populations worldwide believe that media reporters regulate information or that rare events have adverse effects.\n\nAccording to Dudley et al., vaccination is the most effective solution for controlling the COVID-19 pandemic and achieving a high level of immunity in the community.7 Thus, the advantages of vaccination depend mainly on the acceptance rate of the population. The pooled proportion of COVID-19 shows the factors related to a religious perspective that ranged from 52 to 74% in South Asia with the highest rate and in the Eastern Mediterranean Sea with the lowest rate.1 The low rate in Middle Eastern countries is due to a wide range of false beliefs and conspiracies regarding the administration of vaccines. The evaluation showed that the vaccination rate in Middle Eastern countries is higher in males than females. A noticeable trend suggests that males are less likely to believe in theories but are more inclined to receive the COVID-19 vaccine. On the other hand, females are more concerned about safety and efficacy issues related to the doses of COVID-19 vaccines. The distrust in the female population regarding the vaccination of COVID-19 is higher and covers a significant proportion of the population.\n\nThese beliefs among the female population are due to a lack of information related to COVID-19 vaccines; therefore, females show low interest in perceiving the benefits of the COVID-19 vaccine. The effectiveness of COVID-19 vaccines can only be determined through their administration, as they help identify the treatment gap. This determination of gaps helps researchers improve the treatment of COVID-19. In several countries, the vaccine access rate depends on the immunity rate of the population.23 Several countries, such as Africa, have chosen to administer COVID-19 vaccinations after being influenced by positive reviews from populations in other countries.19\n\nThe hesitancy of vaccines due to several pieces of evidence indicates their adverse effects.16 Adverse effects interfere with routine vaccination, mainly by inhibiting the vaccine’s safety efficacy. Paul et al. indicated factors of reluctance to vaccinate against COVID-19 in European countries whose populations are unwilling to take up vaccination.18 Adu et al. stated that healthcare practitioners believe that in the case of a reoccurrence of the pandemic, vaccination is an effective strategy that helps reduce death rates and enhances the possibility that the population will be affected.3 A study found that people worldwide expect long-term efficacy results from COVID-19 vaccines.21 Researchers are willing to conduct more preclinical trials to develop vaccines with greater efficacy and fewer adverse effects to meet the population’s expectations.\n\n\nConclusion and recommendations\n\nIn conclusion, this study aimed to analyse the reluctance to vaccinate COVID-19 patients worldwide based on the current perspective of global trends. Seven articles relevant to this topic were selected and reviewed. The selected articles showed data collection results from different research journals. The researcher focused on several aims and objectives that needed to be met. The most prominent aim of this study was to provide global exploration of and reluctance to COVID-19. The objectives of this study were to explore the current trends related to COVID-19, which is being faced by the global population. The study also highlighted the factors and barriers to accepting the COVID-19 vaccination.\n\nThe analysis of the seven research articles depicted common themes, such as each vaccine having a different level of access attitude towards the regional existence, which primarily depends upon the variability to prevail the vaccine’s effectiveness. The major challenge in implementing COVID-19 vaccination is the unfair distribution and long-term efficacy of vaccination worldwide. A systematic review revealed that the vaccine benefits low-income countries, about 28.3%, with an increasing prevalence rate of COVID-19 globally. In addition, the vaccines equate to a population of approximately 10.94 billion, with generally higher trend rates in urban and suburban areas. The selected studies and articles show that COVID-19 has affected millions of people, and for epidemiologists to make the vaccine, it is a challenge for experts to introduce it worldwide. One study revealed that the unwillingness and uncertainty about receiving the vaccine for COVID-19 is a significant challenge to achieving the targeted coverage required for the population worldwide.\n\nThe researcher encountered several limitations when conducting this systematic review. One of the significant limitations was the risk of bias, including article selection bias, which might have provided insufficient findings to determine the reluctance and factors that promote reluctance among people to the COVID-19 vaccine across the globe. Another major limitation was the unavailability of full-text, high-impact articles, which affected the findings and provided limited results and outcomes.\n\nThis study is a systematic literature review of global findings. However, there is a need to address several regions and countries individually for the study. There is a need to implement other research methods, such as quantitative and qualitative methods, to achieve diversified results in the study. There is a suggestion to create efficient tactics and regulations that can increase the effectiveness of COVID-19 vaccines and diminish people’s hesitancy towards vaccination.11 To achieve this objective, policymakers should create effective policies to promote vaccination. Individuals could be required to present their vaccination cards to ensure that they receive their salary. Addressing the challenges and disadvantages of vaccine implementation is recommended for various organizations and government sectors, including NGOs. Furthermore, the researcher must cater to several factors other than the vaccine, such as managing the potency of the vaccine, the role of the vaccine, and its role in boosting the immunity of a person suffering from COVID-19 and aged people who have less immunity in the body.5 Therefore, there is a need to address the role of doctors, nurses, and other medical staff by conducting a primary qualitative study.\n\nEthical approval and consent were not required.",
"appendix": "Data availability statement\n\nNo Data are associated with this article.\n\nIn conducting this systematic review, we did not generate any extended data beyond what is presented in the main body of the manuscript and its extended materials.\n\nName of the repository: Zenodo.org; Systematic Review of COVID-19 Vaccine Acceptance and Hesitancy: Global Perspectives and Implications, DOI: https://doi.org/10.5281/zenodo.10967086.\n\nThis project contains the following underlying data:\n\n1. covid 19 vaccination UPDATED.docx\n\n2. Flow Diagram.docx\n\n3. PRISMA 2020 checklist.docx\n\nLicense: Systematic Review of COVID-19 Vaccine Acceptance and Hesitancy: Global Perspectives and Implications. By Muhammad Mohsin khan, Noman Shah, Mhran Daie is marked with CC0 1.0 Universal.\n\nPRISMA 2020 checklist for Systematic Review of COVID-19 Vaccine Acceptance and Hesitancy: Global Perspectives and Implications, DOI: https://doi.org/10.5281/zenodo.10967086.\n\n\nReferences\n\nAbdelmoneim SA, Sallam M, Hafez DM, et al.: COVID-19 vaccine booster dose acceptance: Systematic review and meta-analysis. Trop. Med. Infect. Dis. 2022; 7(10): 298. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbu-Odah H, Su J, Musa SS: Unwillingness or reluctance of Palestinians to get the COVID-19 vaccine: the reasons behind it and how to persuade them. Int. J. Infect. Dis. 2022; 119: 53–55. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAdu P, Poopola T, Medvedev ON, et al.: Implications for COVID-19 vaccine uptake: A systematic review. J. Infect. Public Health. 2023; 16: 441–466. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCampos-Mercade P, Meier AN, Schneider FH, et al.: Monetary incentives increase COVID-19 vaccinations. Science. 2021; 374(6569): 879–882. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCaserotti M, Gavaruzzi T, Girardi P, et al.: Who is likely to vacillate in their COVID-19 vaccination decision? Free-riding intention and post-positive reluctance. Prev. Med. 2022; 154: 106885. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFung SY, Yuen KS, Ye ZW, et al.: A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defense: lessons from other pathogenic viruses. Emerg. Microbes Infect. 2020; 9(1): 558–570. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHanney SR, Wooding S, Sussex J, et al.: From COVID-19 research to vaccine application: why might it take 17 months not 17 years and what are the wider lessons? Health Res. Policy Syst. 2020; 18(1): 1–10. Publisher Full Text\n\nKabir MA, Ahmed R, Chowdhury R, et al.: Management of COVID-19: current status and future prospects. Microbes Infect. 2021; 23(4-5): 104832. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu Y, Tang JW, Lam TT: Transmission dynamics of the COVID-19 epidemic in England. Int. J. Infect. Dis. 2021; 104: 132–138. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMillion M, Lagier JC, Gautret P, et al.: Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France. Travel Med. Infect. Dis. 2020; 35: 101738. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNomura S, Eguchi A, Yoneoka D, et al.: Reasons for being unsure or unwilling regarding intention to take COVID-19 vaccine among Japanese people: A large cross-sectional national survey. Lancet Reg. Health West Pac. 2021; 14: 100223. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNorhayati MN, Che Yusof R, Azman YM: Systematic review and meta-analysis of COVID-19 vaccination acceptance. Front. Med. 2022; 8: 3091. Publisher Full Text\n\nNovak N, Tordesillas L, Cabanillas B: Adverse rare events to vaccines for COVID-19: From hypersensitivity reactions to thrombosis and thrombocytopenia. Int. Rev. Immunol. 2022; 41(4): 438–447. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOlu-Abiodun O, Abiodun O, Okafor N: COVID-19 vaccination in Nigeria: A rapid review of vaccine acceptance rate and the associated factors. PLoS One. 2022; 17(5): e0267691. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOur World in Data: Coronavirus (COVID-19) Vaccinations.2022. Reference Source\n\nParimi K, Gilkeson K, Creamer BA: COVID-19 vaccine hesitancy: Considerations for reluctance and improving vaccine uptake. Hum. Vaccin. Immunother. 2022; 18(5): 2062972. PubMed Abstract | Publisher Full Text | Free Full Text\n\nParums DV: Review articles, systematic reviews, meta-analysis, and the updated preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines. Med. Sci. Monit. 2021; 27: e934475–e934471. Publisher Full Text\n\nPaul E, Steptoe A, Fancourt D: Attitudes towards vaccines and intention to vaccinate against COVID-19: Implications for public health communications. Lancet Reg. Health Eur. 2021; 1: 100012. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPetrovič F, Murgaš F, Králik R: Happiness in Czechia during the COVID-19 Pandemic. Sustainability. 2021; 13(19): 10826. Publisher Full Text\n\nSallam M: COVID-19 vaccine hesitancy worldwide: a concise systematic review of vaccine acceptance rates. Vaccines. 2021; 9(2): 160. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTetui M, Grindrod K, Waite N, et al.: Integrating the CARD (Comfort Ask to Relax Distract) system in a mass vaccination clinic to improve the experience of individuals during COVID-19 vaccination: a pre-post implementation study. Hum. Vaccin. Immunother. 2022; 18(5): 2089500. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Health Organisation: WHO Coronavirus (COVID-19) Dashboard.2022. Reference Source\n\nYoneoka D, Eguchi A, Nomura S, et al.: Identification of optimum combinations of media channels for approaching COVID-19 vaccine unsure and unwilling groups in Japan. Lancet Reg. Health West Pac. 2022; 18: 100330. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao J, Zhao S, Ou J, et al.: COVID-19: coronavirus vaccine development updates. Front. Immunol. 2020; 11: 602256. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao Z, Li X, Liu F, et al.: Prediction of the COVID-19 spread in African countries and implications for prevention and control: A case study in South Africa, Egypt, Algeria, Nigeria, Senegal and Kenya. Sci. Total Environ. 2020; 729: 138959. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "277533",
"date": "11 Jun 2024",
"name": "Mohammed Salim Karattuthodi",
"expertise": [
"Reviewer Expertise Vaccine",
"Clinical Pharmacy",
"Infections"
],
"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 editor for providing an opportunity to review this paper. It is well written. However, the following are some of my suggestions:-\nIn the second paragraph of the introduction, the statement \"To date, 12.13 billion vaccine doses have been administered worldwide. \" is better to mention the time period instead of ‘to date’.\nCheck for grammatical errors.\nEven though, the \" Articles published before the COVID-19 pandemic were not included in the study.\" this statement has been mentioned, it is better to mention the from and to date of searching the articles, in the methodology.\nIn the PRISMA flowchart, add the reasons for excluding articles during the second screening.\nThe table can also have a separate column that highlights the acceptance and hesitancy towards vaccines.\nI feel the conclusion can be briefed to include only the core points of the paper.\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? 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": "11856",
"date": "28 Jun 2024",
"name": "Muhammad Mohsin khan",
"role": "Author Response",
"response": "Thank you very much for your insightful comments and the time you dedicated to review. I greatly appreciate your feedback and suggestions. Please find my responses to your comments below: Introduction Revision: Comment: In the second paragraph of the introduction, the statement \"To date, 12.13 billion vaccine doses have been administered worldwide.\" is better to mention the time period instead of 'to date'. Response: Thank you for this suggestion. I have revised the statement to specify the time period. It now reads: \"As of 5th June 2023, 12.13 billion vaccine doses have been administered worldwide.\" Grammatical Corrections: Comment: Check for grammatical errors. Response: I have thoroughly reviewed the manuscript for grammatical errors and made the necessary corrections to enhance clarity and readability. Methodology Enhancement: Comment: Even though \"Articles published before the COVID-19 pandemic were not included in the study.\" this statement has been mentioned, it is better to mention the from and to date of searching the articles, in the methodology. Response: I appreciate your suggestion. The methodology section has been updated to include the specific date range: \"Articles were searched from March 2020 to January 2023.\" PRISMA Flowchart Update: Comment: In the PRISMA flowchart, add the reasons for excluding articles during the second screening. Response: The PRISMA flowchart has been revised to include the reasons for excluding articles during the second screening, providing greater transparency in the study's selection process. Table Modification: Comment: The table can also have a separate column that highlights the acceptance and hesitancy towards vaccines. Response: Thank you for this valuable suggestion. I have updated the table to include a separate column highlighting the acceptance and hesitancy towards vaccines, which should present the data more clearly. Conclusion Streamlining: Comment: I feel the conclusion can be briefed to include only the core points of the paper. Response: I agree that a concise conclusion would be more effective. The conclusion has been revised to focus only on the core points of the paper, ensuring it remains succinct and impactful. Thank you once again for your valuable feedback. Your comments have significantly contributed to improving the quality of this paper."
}
]
}
] | 1
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https://f1000research.com/articles/13-440
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https://f1000research.com/articles/10-858/v1
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26 Aug 21
|
{
"type": "Research Article",
"title": "Factors associated with inadequate urinary iodine concentration among pregnant women in Mbeya region Tanzania.",
"authors": [
"Tedson Lukindo",
"Ray Masumo",
"Adam Hancy",
"Sauli E. John",
"Heavenlight A. Paulo",
"Abraham Sanga",
"Ramadhan Noor",
"Fatoumata Lankoande",
"Elifatio Towo",
"Germana H. Leyna",
"Gemma Bridge",
"Raman Bedi",
"Tedson Lukindo",
"Adam Hancy",
"Sauli E. John",
"Ramadhan Noor",
"Fatoumata Lankoande",
"Elifatio Towo",
"Germana H. Leyna",
"Raman Bedi"
],
"abstract": "Background: Deficient and excess iodine intake during pregnancy can lead to serious health problems. In Tanzania, information available on iodine status during pregnancy is minimal. The aim of this study was to assess the iodine status and its association with sociodemographic factors in pregnant women in the Mbeya region, Tanzania. Method: A cross sectional survey involving 420 pregnant women (n=420) aged between 15-49 years registered in antenatal care clinics was conducted. Data were collected via interviews and laboratory analysis of urinary iodine concentration (UIC). Results: Median UIC was 279.4μg/L (+/-26.1) to 1915μg/L. Insufficient iodine intake (UIC below 150μg/L) was observed in 17.14% of participants, sufficient intake in 24.29% and 58.57% had intakes above the recommended level (>250μg/L). Rungwe district council (DC) had the highest proportion of patients (27.9%) with low iodine levels, while Chunya and Mbarali DCs had the greatest proportion of those with UIC’s, over the WHO recommended level. Fish consumption and education status were associated with increased risk of insufficient iodine while individuals in Mbalali DC aged between 35-49 years were associated with increased risk of UIC above recommended level. Conclusion: Both deficient and excess iodine intake remains a public health problem, especially in pregnant women in Tanzania. Therefore, educational programs on iodine intake are needed to ensure this population has an appropriate iodine intake to prevent any health risks to the mother and the unborn child.",
"keywords": [
"Iodine deficiency",
"medium urine iodine concentration",
"pregnant women",
"socio-demographic and dietary risk factors"
],
"content": "Introduction\n\nIodine deficiency is a significant global public health concern.1 This element is found in hormones produced by the thyroid gland namely, triiodothyronine (T3) and thyroxine (T4),1,2 and must be consumed in the diet as it cannot be made naturally in the body.1 A diet low in iodine results in deficiencies that can occur at any age. If iodine requirements are not met, the thyroid is unable to produce thyroid hormone in sufficient quantities, leading to iodine deficiency disorders (IDD) with associated functional and developmental abnormalities.3\n\nIn terms of daily intake of iodine, the World Health Organization (WHO) recommends 90 μg for children aged 0-5 years; 120 μg for children aged 6-12 year; and 150 μg for those over 12 years. Pregnant and lactating women are recommended 250 μg4 daily. By ensuring that individuals have an adequate intake of iodine in their diets, IDDs can be prevented.5 Although cretinism is the most severe form of iodine deficiency, minor iodine deficiency can also result in reduced intellectual ability, limited work capacity due to mental and neurological impairment.4 In 1994, from the 1572 million people globally who suffered from iodine deficiency (28.9% of global population), 11.2 million were affected by overt cretinism, and 43 million people had at least some degree of intellectual impairment.5\n\nIn Tanzania, the most recent figures indicate that more than 40% of the population live in geographical regions prone to iodine deficiency.6 The prevalence of IDD is greatest in the highland regions such as Iringa, Arusha, Mbeya, Rukwa and Ruvuma.7 The Tanzania Demographic and Health Survey (TDHS) indicates that such IDD variations occur largely because of differences in the use of adequately iodised salt (15+ ppm), with households in urban areas more likely to use adequately iodised salt (81%) than those in rural areas (51%) such as the highlands.7 As recommended by WHO, Iodine Global Network (IGN) and United Nations Children’s Fund (UNICEF), median Urinary Iodine Concentration (UIC) is considered the most practical biochemical marker for the assessment and monitoring of iodine nutrition in the population.8 According to the National IDD survey conducted in 2004, about 25% of primary school children in Tanzania had UIC below 100 μg/L.6\n\nUniversal salt iodization (USI), whereby all the salt used for human consumption is iodized, is the most used intervention to increase iodine intake.9 This intervention is widespread, as 68% of households have access to iodized salt.10 USI is an effective way of delivering iodine to individuals and in term, improving cognition in populations exposed to iodine deficiency.10,11 USI is also affordable, with annual costs of salt iodization estimated at USD 0.02-0.05 per child, while the costs to prevent child death is estimated at USD 1000. There are also large gains in per Disability-Adjusted Life Years (DALYs), at USD 34-36.12 Before USI, it was estimated that iodine deficiency leads to losses of USD 35.7 billion in the countries affected, which is significant when compared with an estimated cost of USD 0.5 billion for USI, representing a cost benefit ratio of over 70:1.13\n\nIn 1995, Tanzania legislation on USI was enacted.14 This was later revised in 2010, and now, all salt consumed by animals and humans in the country is fortified with iodine. Enforcement of this legislation is challenging in Tanzania, especially in areas where small-scale salt producers operate. As a result, iodized salt is not widely available. Further, although household coverage with iodized salt is above 80% nationally, the coverage of adequately iodized salt is at 47% across Tanzania.15\n\nNutritional deficiencies are prevalent among pregnant women in Tanzania, particularly, in areas of low socioeconomic status. However, there is a dearth of information regarding the burden of, and factors associated with iodine deficiency in this population. In 2010 and 2015, the TDHS reported that the prevalence of iodine deficiency amongst pregnant women was 54%, however, the results of the TDHS were heterogeneous across the regions.16,17 There are also concerns relating to excessive iodine consumption in pregnancy, because although high iodine intakes are well tolerated by most healthy individuals, in some, excess intake can lead to thyroid conditions such as hyperthyroidism, hypothyroidism, and/or thyroid autoimmunity.18,19 As insufficient and excessive iodine consumption in pregnancy can result in negative health impacts, it is imperative to investigate current iodine levels and to assess how current USI interventions affect iodine intake, especially in highland areas of Tanzania. It is also necessary to set upper as well as lower limits for maternal iodine intake to ensure optimal health outcomes are achieved.19 Given the above, this study aimed to firstly, determine the likelihood of iodine levels being above or at recommended levels in the urine (μg/L) of pregnant women in their second trimester. Secondly. to assess the likelihood of IDD or otherwise, differing across socioeconomic groups and locations in Tanzania.\n\n\nMethods\n\nThis was a cross-sectional survey involving pregnant women aged 15-49 years registered in antenatal care clinics (ANC). Study participants were recruited in all seven district councils (DC) of the Mbeya region (Chunya district, Ileje district, Mbarali district, Mbeya urban district, Mbozi district, Momba district and the Rungwe district), from September until October 2020. The Mbeya region has 17 hospitals, 23 health centres, and 278 dispensaries, where 251 health facilities provide reproductive and child health services. The study was conducted at 42 Reproductive and Child Health (RCH) clinics in the seven districts of the Mbeya region. The selected RCH clinics provide services to approximately 1036 pregnant women.\n\nPregnant women aged 15-49 years that were within their first and second trimesters (less than 28 weeks of gestation), who attended ANC in the Mbeya region were recruited into the study. Overall, 574 participants were invited to participate, from which 420 (n = 420) agreed to take part. Participants in their second trimester, a period during which fetal neurodevelopment is impacted by adequate maternal thyroid function, were included. To eliminate the effects of gestational age on thyroid hormone, participants beyond eight weeks of gestation were excluded. Additionally, individuals who did not give consent, or were not able to communicate due to illness, and those taking medication were excluded. The sample size for the whole survey was pre-calculated based on the Lwanga and Lemeshow formula.20\n\nIn the Mbeya region, 251 governmental and faith-based health facilities that provided RCH services were included in a list, which was used to randomly select health facilities per district. In the survey, 42 facilities were randomly selected to take part, with two additional sites later invited, giving a total of 44 facilities in the final survey. Probability proportional to size was performed, due to the sampling frame of public health facilities in Mbeya, to allocate the number of facilities per district in the survey. Next, pregnant women from each selected health facility were invited to take part in the research. All pregnant women attending the ANC were asked to complete an eligibility form. Those that were eligible to take part were included in a Systematic Random Sampling procedure. This was done by obtaining an accurate and complete list of the pregnant women who had attended ANC in each health facility, and randomly selecting the required number of women per facility.\n\nData were collected through interviews guided by a structured questionnaire and, laboratory analysis of urine samples. A standard structured questionnaire was constructed in English and translated into Kiswahili, a language that is spoken by almost 95% of Tanzanians (see Extended data).21 To ensure the quality of the translation, back-translation was performed by independent translators and reviewed by field staff in Mbeya. Pre-testing was done to evaluate the quality of the translations in terms of comprehensibility, readability, and relevance to assess face validity.\n\nThe interviews were administered by a health professional trained in face-to-face interviews with participants, before the collection of urine samples. Initial interviews were administrated to determine various social demographic characteristics and dietary factors concerning iodine status, including participant’s age, marital status, education, household assets possessions, socioeconomic status, parity, stage of pregnancy, and dietary habits.\n\nMost of iodine consumed in the diet (90%) is lost through urine. As such UI is used as an indicator of iodine intake, expressed either as (μg/L), in terms of its relationship to creatinine excretion (μg iodine/g creatinine), or as 24-hour excretion (μg/day), termed urinary iodine excretion (UIE). It is impractical to collect 24-hour samples in field studies, therefore UI acts as a practical alternative to assess UI (expressed as the median, in μg/L) in a representative sample of the target group. After interviews were completed, a trained member of nursing staff took spot urine samples from consented participants. Urine samples were collected in a disposable plastic screw caped 100ml urine container. The urine samples were transported to a temporary laboratory for processing and shipment to central Tanzania Food and Nutrition Centre (TFNC) laboratory for analysis. At the temporary laboratory, the urine samples were transferred into screw-capped plastic vials and frozen at −20°C until shipped to TFNC laboratory for analysis. The urine samples were analyzed using the ammonium persulfate digestion method, as previously described by Sandell-Kolthoff reaction.22 TFNC laboratory is registered and successfully participated in the quality assurance program for Ensuring the Quality of Urinary Iodine Procedures (EQUIP)23 offered by the Centres for Disease Control and Prevention (CDC), Atlanta, Georgia, USA. The assay accuracy was assessed using reference quality-control urine specimens obtained from the CDC. The assay detection limit was <5.0 μg/L with the coefficient of variation <10%, when compared to the reference method.23\n\nOutcome/response variable\n\nMedian UCI as a response variable was split into three categories as per WHO recommended level of iodine micronutrient. A new variable called medium urine iodine concentration (MUIC) was developed to indicate the level of iodine in urine (μg/L) (see underlying data).21\n\nMUIC 1 (Iodine <150μg/L) = Insufficient/deficiency iodine\n\nMUIC 2 (150< Iodine <249 μg/L) = Sufficient/adequacy iodine\n\nMUIC 3 (Iodine >250 μg/L) = Excessive iodine intake\n\nIndependent variables/predictors\n\nThe study includes a set of independent variables to understand the extent and variations between the levels of iodine micronutrients among the participants. Socio-demographic variables assessed included age, residency (district), education level, occupation status, number of pregnancies, visits to the ANC and, upper mid-arm circumference (MUAC), which is the most accurate way to measure fat-free mass outside of a laboratory. Household wealth was also assessed. To do so, durable household assets that indicate wealth such as a radio, television, and telephone were recorded as (1) “available and in working condition” or (0) “not available and/or not in working condition.” Principal component analysis, PCA was then conducted to categorize households into five quartiles of wealth, with 1 being the lowest and 3 the highest. Diet, in specific consumption of certain foods, such as fish, dairy products, processed meat and, refined and baked foods were also assessed among the participants, using 24-hour recalls.\n\nThe data were analyzed using Stata v 15.1(RRID: SCR_012763). Stata is a proprietary software but an open-access alternative in which the sequence could have been generated is Microsoft Excel (RRID: SCR_016137). Descriptive statistics were used to summarize the data of study participants. Pearson’s chi-square test and p-values were used to test for the significance of each of the potential risk factors in bivariate analysis. Multinomial logistic regression models were used to adjust for cofounders and predict the true association between the dependent and independent variables. All tests were two-tailed, and the significance level was set at p ≤ 0.05.\n\nEthical clearance was obtained from the National Institute for Medical Research (NIMR) with reference number NIMR/HQ/R.8a/Vol. IX/2589 and appropriate authorization was given from the Regional, Council and health facility level. All eligible subjects were given information about the survey and were asked to sign a written informed consent form before participation.\n\n\nResults\n\nIn this study, 420 agreed to participate (response rate of 73 %), with the mean age of 25.49 (± 6.37) years. In terms of demographics, 70% of participants had primary education, 75% has been pregnant more than once, 68% reported that they consumed fish and, more than 90% consumed dairy products. Improved source of water was reported by 71% of the participants (Table 1).\n\nThe median UIC in the present study was 279.4μg/L, and it ranged from 26.1-1915μg/L. According to the UIC results, 17.14% of participants had an insufficient iodine intake, 24.29% had sufficient/adequate urine iodine concentration, and 58.57% had above the recommended level of iodine in urine (Table 1).\n\nOf 215 participants aged between 15-24 years, 17% had UIC (0–149 μg/l) that would be considered inadequate, and 55.8% had UIC (>250 μg/l) above the recommended levels. Table 2 presents a cross-tabulation of the prevalence of median UIC, MUIC and various independent factors. Chunya and Mbarali DCs have the highest percentage (above 70%) of the WHO recommended UIC among the participants in the sample. Rungwe DC had the highest percentage (27.9%) of participants with inadequate urine iodine concentrations. From the 133 participants who had fish in their diet, UIC was inadequate in 23%, adequate in 19.4%, and 56.9% had above the recommended level.\n\nThe fitted models and the estimated effects from the multivariate analysis are presented in Table 3. The chi-square model (63.51) was 0.0176, with p < 0.05.\n\n* Represents p value: *p<0.05.\n\nThe predicted probability of having inadequate urine iodine level was 2.60 (95% CI 1.31-5.15), in participants who consumed freshwater fish. Additionally, inadequate iodine level was 0.29 (95 % CI 0.08-0.99) in participants who had a primary school education. The probability of having increased iodine levels amongst participants living in Mbarali DC was 4.09 (95% CI 1.85- 9.01), whilst for individuals aged 35-49 years, the probability was 2.51 (95% CI 0.99-6.33). The likelihood of having an inadequate iodine level based on DC, resulted in a significant likelihood of having above recommended iodine level for individuals in Mbarali DC [4.09 (95% CI 1.85-9.01)], whilst those living in Rungwe DC had a significant (borderline) likelihood of having inadequate iodine levels [2.43 (95% CI 0.95-6.19)].\n\n\nDiscussion\n\nThis is the first population-based cross-sectional study to assess the magnitude of iodine status and the association with socio-demographic factors and diet in Tanzanian pregnant women. The findings of the study are important since iodine deficiency is the most prevalent micronutrient deficiency, affecting 28.9% of the world population,24 particularly affecting women living in developing countries.25 Iodine deficiency in Tanzania is also high with the most recent figures indicating that more than 40% of the population in the country lives in geographical regions prone to iodine deficiency.6 However, this data is largely outdated, as more recent data as well as the most recent efforts to reduce iodine deficiency have focused on primary school children in Tanzania.6 Whilst the iodine micronutrient status among pregnant women has been overlooked in recent years.\n\nIn this study, pregnant women living in the Mbarali district were more likely to be above the recommended level of UIC [4.09 (95% CI 1.85-9.01)], particularly among individuals aged between 35-49 years [2.51 (95% CI 0.99-6.33)]. Thus, it is important to monitor thyroid function and its associated disorders in this population. Contrary to these results, in 2010, a reanalysis of the Tanzania demographic and health survey reported 54% of pregnant women with iodine deficiency.16 The discrepancy could be attributed to differences in study methodologies as well as the 10-year lapse between the studies, since significant USI interventions were applied in this period.\n\nIn this study a strong association between consumption of freshwater fish and UIC of <150μg/l [odd ratio = 2.60 (95% CI 1.31-5.15)], indicated that pregnant women who consumed fish were at higher risk of iodine deficiency. This finding could be explained by the notion that iodine levels in freshwater fish depend on the locality and the regularity of consumption of fish.26,27 Moreover, during pregnancy there are variations in the functionality of the thyroid. This can increase the risk of inadequate iodine intake for some mothers. As such, predicting UIC based on usage of iodized salt alone, may not be accurate.28–30 Other studies have documented that freshwater fish may contain Iodine in levels that can improve daily Iodine intake.26\n\nIn countries with successful USI programs, studies have reported an optimal median UIC in pregnant women. As such, USI remains the most cost-effective strategy for achieving reduced IDD.31,32 However, the full implementation of USI remains a challenge in many sub–Saharan African countries including Tanzania,33 largely due to the lack of adequate enforcement and, the inadequate monitoring of small-scale salt producers who often do not comply with USI legislation.6\n\nThis analysis also indicated that pregnant women who had a primary school education were at higher risk of iodine deficiency [odd ratio= 0.29 (95% CI 0.08-0.99)], However, further studies are needed to investigate this association. Excessive iodine intake in pregnant women is also an important area of current research.34,35 The WHO recommended an increased iodine intake for pregnant women, although evidence is weak.36 However, detrimental effects from more than adequate and excessive iodine intake have been reported in general populations.37–39 Shi et al. have reported on the associations between UIC and thyroid health among pregnant women and recommend a lower limit for maternal iodine intake during pregnancy than that currently advised by the WHO.40 This is also an area in need of further investigation. The question remains if pregnant women in Mbarali district should continue using iodinated salt, and if so at what concentration.\n\nThe strength of this study is in its large population-based sample size. The study limitations are as follows, first, the use of UIC to determine individual iodine status could be limited due to the potential for misclassification of participants because of day-to-day variations. Second, UIC reflects recent iodine intake or exposure rather than chronic individual iodine status. Additionally, the use of iodized salt was not assessed in this study. Finally, it would have been useful to have a non-pregnant control group to help ascertain whether lower UI concentrations during pregnancy could be attributed to pregnancy itself or the diet.\n\n\nConclusion\n\nThe aim of this study was to explore iodine levels in pregnant women living in the Mbeya region of Tanzania. Findings indicate that 17.14% of participants had an insufficient iodine intake whilst, 24.29% had sufficient/adequate urine iodine concentration, and 58.57% had above the recommended levels of iodine. There were differences found between district councils, with the Rungwe DC having the highest percentage (27.9%) of participants with inadequate urine iodine concentrations. Protective factors for IDD included consumption of freshwater fish and having a primary education, whilst factors increasing the risk of excessive iodine intake included being older in age (35-49 years). Due to these findings, this study recommends strategic efforts to ensure that the current USI program addresses the problem of iodine deficiency in pregnant women, and monitor excessive iodine exposure that might have detrimental effects during pregnancy.\n\n\nData availability\n\nOpen Science Framework (OSF): Factors associated with inadequate urinary iodine concentration among pregnant women in Mbeya region Tanzania.\n\nDOI: https://osf.io/7ysb9/.21\n\nThis project contains the following underlying data:\n\n• MBMNS_MUIC10082021: This is the SPSS database file that contained all the laboratory assessment variables for the medium urine iodine concentrations.\n\nThis project also contains the following extended data:\n\n• Questionnaire English version: This file contains all the questions used to interview pregnant women in Mbeya.\n\n• Questionnaire Swahili version: This file is the Swahili version of Questionnaire.\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\nAuthor contributions\n\nConceptualization, TL, RM., AH. SEJ and GHL; project administration and resources, AS, RN, FK and GHL; formal analysis and writing—original draft, TL, RM, AH, SEJ, HAP, AS, RN, FK, ET and GHL; reviewed and edited the manuscript. GB and, RB. All authors: Reviewed and agreed upon the final manuscript.",
"appendix": "Acknowledgments\n\nWe sincerely appreciate health workers assistance in the laboratory data collection and the participation of all pregnant women in this study.\n\n\nReferences\n\nZimmermann MB, Jooste PL, Pandav CS: Iodine-deficiency disorders. The Lancet. 2008; 372: 1251–1262. PubMed Abstract | Publisher Full Text\n\nChung HR: Iodine and thyroid function. Ann Pediatr Endocrinol Metab. 2014; 19: 8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKapil U: Health consequences of iodine deficiency. Sultan Qaboos Univ Med J. 2007; 7: 267–272. PubMed Abstract | Free Full Text\n\nWHO: Eliminating iodine deficiency worldwide is within reach.Reference Source\n\nEastman CJ, Zimmermann MB: The Iodine Deficiency Disorders. Endotext. MDText.com, Inc.; 2000.\n\nAssey VD, et al.: Tanzania national survey on iodine deficiency: Impact after twelve years of salt iodation. BMC Public Health. 2009; 9: 1–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNBS/Tanzania, N. B. of S.- & Macro, I: Tanzania Demographic and Health Survey 2010.2011.\n\nyesAssessment of iodine deficiency disorders and monitoring their elimination Third edition A guide for progrAmme mAnAgers. .\n\nVenkatesh Mannar MG, Bohac L: Achieving Universal Salt Iodization: Lessons Learned and Emerging Issues.\n\nAppiah PK, Yanbom CT, Ayanore MA, et al.: Iodine Content of Salt Use after Years of Universal Iodization Policy and Knowledge on Iodized Salt among Households in the Sissala East Municipality in Upper West Region of Ghana. J Food Quality. 2020; 2020.\n\nEastman CJ, Zimmermann MB: The Iodine Deficiency Disorders. Endotext. MDText.com, Inc.; 2000.\n\nZimmermann MB, Andersson M: Assessment of iodine nutrition in populations: past, present, and future. 2012. Publisher Full Text\n\nGorstein JL, Bagriansky J, Pearce EN, et al.: Estimating the Health and Economic Benefits of Universal Salt Iodization Programs to Correct Iodine Deficiency Disorders. Thyroid. 2020; 30: 1802–1809. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTanzania legislation on USI: 1995; accessed 03/08/2021.Reference Source\n\nAssey V, Mwanditani R, Kimbioka S: IDD NEWSLETTER NOVEMBER 2013 TANZANIA. 2013: 9.\n\nMtumwa AH, Ntwenya JE, Paul E, et al.: Socio-economic and spatial correlates of subclinical iodine deficiency among pregnant women age 15-49 years in Tanzania. BMC Nutrition. 2017; 3: 1–10. Publisher Full Text\n\nBa DM, et al.: Factors Associated with Urinary Iodine Concentration among Women of Reproductive Age, 20-49 Years Old, in Tanzania: A Population-Based Cross-Sectional Study. Current Developments in Nutrition. 2020; 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFarebrother J, Zimmermann MB, Andersson M: Excess iodine intake: sources, assessment, and effects on thyroid function. Ann N Y Acad Sci. 2019; 1446: 44–65. PubMed Abstract | Publisher Full Text\n\nLee SY, Pearce EN: Reproductive endocrinology: Iodine intake in pregnancy-even a little excess is too much. Nat Rev Endocrinol. 2015; 11: 260–261. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLemeshow S, Hosmer DW, Klar J, et al.: Adequacy of sample size in health studies. 1990.\n\nMasumo R: IMAN. Retrieved from osf.io/7ysb9. 2021, August 13.\n\naccessed 03/08/2021.Reference Source\n\nCaldwell KL, et al.: EQUIP: a worldwide program to ensure the quality of urinary iodine procedures Springer-Verlag 2005. Accred Qual Assur. 2005; 10: 356–361.\n\nAndersson M, Karumbunathan V, Zimmermann MB: Global iodine status in 2011 and trends over the past decade. J Nutr. 2012; 142: 744–750. PubMed Abstract | Publisher Full Text\n\nGlinoer D: The importance of iodine nutrition during pregnancy. Public Health Nutrition. 2007; 10: 1542–1546 (Public Health Nutr).\n\nEckhoff KM, Maage A: Iodine Content in Fish and Other Food Products from East Africa Analyzed by ICP-MS. J Food Composition Analysis. 1997; 10: 270–282. Publisher Full Text\n\nKrela-Kaźmierczak I, et al.: Is there an ideal diet to protect against iodine deficiency? Nutrients. 2021; 13: 1–15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGlinoer D: Pregnancy and iodine. Thyroid. 2001; 11: 471–481. PubMed Abstract | Publisher Full Text\n\nMarchioni E, et al.: Iodine deficiency in pregnant women residing in an area with adequate iodine intake. Nutrition. 2008; 24: 458–461. PubMed Abstract | Publisher Full Text\n\nGowachirapant S, et al.: Urinary iodine concentrations indicate iodine deficiency in pregnant Thai women but iodine sufficiency in their school-aged children. J Nutri. 2009; 139: 1169–1172. PubMed Abstract | Publisher Full Text\n\nMao G, et al.: Iodine deficiency in pregnant women after the adoption of the new provincial standard for salt iodization in Zhejiang Province, China. BMC Pregnancy and Childbirth. 2018; 18: 1–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nReaching optimal iodine nutrition in Pregnant and Lactating Women and Young Children. http\n\nBa DM, et al.: Factors Associated with Urinary Iodine Concentration among Women of Reproductive Age, 20-49 Years Old, in Tanzania: A Population-Based Cross-Sectional Study. Curr Dev Nutr. 2020; 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPearce EN, Lazarus JH, Moreno-Reyes R, et al.: Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns. Am J Clin Nutr. 2016; 104: 918S–923S. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLeung AM, Braverman LE: Consequences of excess iodine. Nat Rev Endocrinol. 2014; 10: 136–142. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAndersson M, de Benoist B, Delange F, et al.: Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: Conclusions and recommendations of the Technical Consultation. Public Health Nutrition. 2007; vol. 10: 1606–1611. Cambridge University Press.\n\nGuan H, et al.: Influence of iodine on the reference interval of TSH and the optimal interval of TSH: Results of a follow-up study in areas with different iodine intakes. Clin Endocrinol. 2008; 69: 136–141. PubMed Abstract | Publisher Full Text\n\nSun X, Shan Z, Teng W: Effects of increased iodine intake on thyroid disorders. Endocrinol Metab (Seoul). 2014; 29: 240–247. PubMed Abstract | Publisher Full Text | Free Full Text\n\nConnolly RJ, Vidor GI, Stewart JC: Increase in thyrotoxicosis in endemic goitre area after iodation of bread. Lancet. 1970; 295: 500–502. PubMed Abstract | Publisher Full Text\n\nShi X, et al.: Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: A cross-sectional study of 7190 pregnant women in China. J Clin Endocrinol Metab. 2015; 100: 1630–1638. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "141642",
"date": "25 Jul 2022",
"name": "Joyce Kinabo",
"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\nAbstract:\nUse of the word 'insufficient' should be consistent through out the article.\n\nConclusion does not state explicitly the factors associated with insufficient/sufficient UIC.\nIntroduction:\nProvide explanation as to why highland regions have highest prevalence of IDD considering that Tanzania has been implementing salt iodisation programmes for many years?\nMethod:\nChange 'Ante-natal Care Clinics' to 'Reproductive and Health Clinics' and use it consistently through out the document.\n\nExplain adequately how sampling procedure was carried out.\n\nWas the questionnaire pre-tested before translation?\n\n\"interviews were done by health professional\" - which cadre?\n\nProvide more information about the conditions for storage of the urinary samples in the field, transportation and storage at the laboratory before analysis and for how long were the samples stored before analysis. What distance from the field to the laboratory? This is important because iodine in urine is know to undergo changes after some time.\n\nWas their any effort to ensure that women at various stages of pregnancy were well represented in the sample? It will also be useful to know of the sample size recruited, what was the stage of pregnancy for each participant? This information is missing.\n\nWhy Mbeya region? Provide justification.\nResults:\nArea of residence seemed to have an influence on iodine status of pregnant women, it was expected to see a good description of the study areas in this manuscript. The information is missing. Could the authors strive to provide this information?\n\nIt will also be useful to know the stage of pregnancy (1st , 2nd, 3rd, trimester) of participants and if there were any association/interaction between area of residence, other factors and UIC.\n\nPresentation of Tables should be improved; instead of brackets, authors could include columns for easy of reading.\n\nWhat was the consumption of iodised salt? This could be one of the contributing factors to high levels of UIC observed in some areas of the study. But also consumption of foods especially vegetables of the brassica group that are known to have compounds that interact with iodine in the gut.\n\nClarification about consumption of processed meat.\n\nClearly stipulate factors that are associated with UIC in this section. Factors are not very clear.\nDiscussion:\nHow were the identified factors influenced iodine status? These have not been adequately articulated in this manuscript.\n\nWas the use of iodised salt investigated in the present study? What is the level of consumption among pregnant women? What is the availability and accessibility to iodised salt in the study areas?\n\nAuthors indicated some strengths of the study; large sample size; but also identified limitations? One of the limitations was that they did not investigate use of iodised salt in the study area. This is a serious omission considering that iodised salt contributes to iodine intake and therefore UIC at least for a large part of the population. Additionally, there was no control group, which again raises concern over the design of this study.\n\nConclusion: It is a repeat of statement of results and not conclusion. Authors should look at the objectives of the study and provide a concrete conclusion as to whether the objectives were attained and what are the implications to individual women and society in general.\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": "8615",
"date": "12 Sep 2022",
"name": "Ray Masumo",
"role": "Author Response",
"response": "We appreciate the time and effort that you and the reviewer have dedicated to providing valuable feedback on our manuscript. Thank you very much. Here is a point-by-point response to the reviewer's comments and concerns. Abstract Comment 1: The use of the word 'insufficient' should be consistent throughout the article. Response: The word ‘insufficient’ instead of ‘deficiency’ will be used throughout the manuscript. Comment 2: Conclusion does not state explicitly the factors associated with insufficient/sufficient UIC Response: The conclusion will carefully be rephrased and show factors associated with insufficient/sufficient UIC. Introduction: Comment 1: Provide an explanation as to why highland regions have highest prevalence of IDD considering that Tanzania has been implementing salt iodisation programs for many years? Response: The explanation has been provided on page 11, discussion section, paragraph 4 ‘However, the full implementation of USI remains a challenge in many sub–Saharan African countries including Tanzania, largely due to the lack of adequate enforcement and, the inadequate monitoring of small-scale salt producers who often do not comply with USI legislation’. Method: Comment 1: Change 'Ante-natal Care Clinics' to 'Reproductive and Health Clinics' and use it consistently throughout the document. Response: The word 'Ante-natal Care Clinics' will replace 'Reproductive and Health Clinics' throughout the document. Comment 2: Explain adequately how sampling procedure was carried out. Response: We agree, and the sampling procedures will be explained in more detail. Comment 3: Was the questionnaire pre-tested before translation? Response: Thank you very much for pointing this out. The questionnaire was pre-tested after translation. Comment 4: Interviews were done by health professional\" - which cadre? Response: Interviews were done by trained Nurse Midwives (we will specify the cadre of health professionals). Comment 5: Provide more information about the conditions for storage of the urinary samples in the field, transportation, and storage at the laboratory before analysis and for how long were the samples stored before analysis. What distance from the field to the laboratory? This is important because iodine in urine is known to undergo changes after some time. Response: We agree - more information on the conditions of the urinary samples stored in the field, transportation, and storage at the laboratory before analysis will be added. Comment 6: Was their any effort to ensure that women at various stages of pregnancy were well represented in the sample? It will also be useful to know of the sample size recruited, what was the stage of pregnancy for each participant? This information is missing. Response: Thank you very much for pointing this out. The inclusion and exclusion criteria of this study were mentioned on page 4, paragraph 2 ‘Participants in their second trimester, a period during which fetal neurodevelopment is impacted by adequate maternal thyroid function, were included. To eliminate the effects of gestational age on thyroid hormone, participants beyond eight weeks of gestation were excluded. Comment 7: Why Mbeya region? Provide justification. Response: This study is the part of IMAN project piloted in Mbeya and supported by the UNICEF-Tanzania and the Ministry of Health - Tanzania aims to demonstrate how the country can sustainably scale up delivery of a comprehensive package of interventions to improve maternal nutrition (Interventions, Platforms, and Enabling Environment/System strengthening). Results: Comment 1: Area of residence seemed to have an influence on iodine status of pregnant women, it was expected to see a good description of the study areas in this manuscript. The information is missing. Could the authors strive to provide this information? Response: We agree and more information on the area of residence will be added. Comment 2: It will also be useful to know the stage of pregnancy (1st, 2nd, 3rd, trimester) of participants and if there were any association/interaction between area of residence, other factors and UIC. Response: The study participants were only pregnant women in the second trimester and the reason behind this was to avoid the effects of gestational age on thyroid hormone. Comment 3: Presentation of Tables should be improved; instead of brackets, authors could include columns for easy of reading. Response: We agree with this comment and will remove the bracket. Comment 4: What was the consumption of iodised salt? This could be one of the contributing factors to high levels of UIC observed in some areas of the study. But also consumption of foods especially vegetables of the brassica group that are known to have compounds that interact with iodine in the gut. Response: Consumption of iodized salt and vegetables of the Brassica group will be the limitation of the study. Comment 5: Clarification about consumption of processed meat. Response: Here we referred to meats that have been preserved by smoking, salting, curing, or addition of chemical preservatives. Comment 6: Clearly stipulate factors that are associated with UIC in this section. Factors are not very clear. Response: We agree with this comment and will rephrase the paragraphs to stipulate clearly the factors associated with UIC. Discussion: Comment 1: How were the identified factors influenced iodine status? These have not been adequately articulated in this manuscript. Response: We agree with this comment and will rephrase the discussion section to articulate clearly on factors that influence iodine status. Comment 2: Was the use of iodised salt investigated in the present study? What is the level of consumption among pregnant women? What is the availability and accessibility to iodised salt in the study areas? Response: We have noted these observations and, they will be part of the study's limitations. Comment 3: Authors indicated some strengths of the study; large sample size; but also identified limitations? One of the limitations was that they did not investigate use of iodised salt in the study area. This is a serious omission considering that iodised salt contributes to iodine intake and therefore UIC at least for a large part of the population. Additionally, there was no control group, which again raises concern over the design of this study. Response: Thank you so much for pointing this out. We will add more information that clarifies the limitation of our study design. Comment 4: Conclusion: It is a repeat of statement of results and not a conclusion. Authors should look at the objectives of the study and provide a concrete conclusion as to whether the objectives were attained and what are the implications to individual women and society in general. Response: We agree, and we will carefully rewrite the conclusion section based on the study objectives."
},
{
"c_id": "8663",
"date": "12 Sep 2022",
"name": "Ray Masumo",
"role": "Author Response",
"response": "We appreciate the time and effort that you and the reviewer have dedicated to providing valuable feedback on our manuscript. Thank you very much. Here is a point-by-point response to the reviewers’ comments and concerns. Abstract Comment 1: Use of the word 'insufficient' should be consistent throughout the article. Response: We agree with this comment and have incorporated your suggestion throughout the manuscript. Comment 2: Conclusion does not state explicitly the factors associated with insufficient/sufficient UIC Response: Thank you for pointing this out. We agree with this comment and have rewritten the conclusion as suggested. Introduction: Comment 1: Provide explanation as to why highland regions have highest prevalence of IDD considering that Tanzania has been implementing salt iodisation programmes for many years? Response: Agree. We have revised the introduction section to clearly emphasize this point. Method: Comment 1: Change 'Ante-natal Care Clinics' to 'Reproductive and Health Clinics' and use it consistently throughout the document. Response: We agree with this comment and have incorporated your suggestion throughout the manuscript. Comment 2: Explain adequately how sampling procedure was carried out. Response: We agree, and have rewritten the sampling procedures. Comment 3: Was the questionnaire pre-tested before translation? Response: Thank you very much for pointing this out. The questionnaire was pre-tested after translation. Comment 4: Interviews were done by health professional\" - which cadre? Response: Interviews were done by a trained Nurse Midwife. We have incorporated this suggestion throughout the manuscript. Comment 5: Provide more information about the conditions for storage of the urinary samples in the field, transportation and storage at the laboratory before analysis and for how long were the samples stored before analysis. What distance from the field to the laboratory? This is important because iodine in urine is known to undergo changes after some time. Response: We agree with this comment and have added more information on the conditions of the urinary samples stored in the field, transportation, and storage at the laboratory before analysis. Comment 6: Was their any effort to ensure that women at various stages of pregnancy were well represented in the sample? It will also be useful to know of the sample size recruited, what was the stage of pregnancy for each participant? This information is missing. Response: Thank you very much for pointing this out. The inclusion criteria of this study clearly indicated that ‘To eliminate the effects of gestational age on thyroid hormone, participants beyond eight weeks of gestation were excluded. Comment 7: Why Mbeya region? Provide justification. Response: Thank you for pointing this out and we have added the following statement in the manuscript for clarity. This study is part of the project on improving maternal and adolescent nutrition in Mbeya supported by UNICEF Tanzania and the Ministry of Health- Tanzania. Results: Comment 1: Area of residence seemed to have an influence on iodine status of pregnant women, it was expected to see a good description of the study areas in this manuscript. The information is missing. Could the authors strive to provide this information? Response: Thank you for pointing this out and we have added a sub-section of the study site in the methods section. Comment 2: It will also be useful to know the stage of pregnancy (1st, 2nd, 3rd, trimester) of participants and if there were any association/interaction between area of residence, other factors and UIC. Response: You have raised an important point here. However, we believe that excluding participants of beyond eight weeks of gestation was more appropriate to avoid the effects of gestational age on thyroid hormone. Comment 3: Presentation of Tables should be improved; instead of brackets, authors could include columns for easy of reading. Response: We agree with this comment and have incorporated your suggestion. Comment 4: What was the consumption of iodised salt? This could be one of the contributing factors to high levels of UIC observed in some areas of the study. But also consumption of foods especially vegetables of the brassica group that are known to have compounds that interact with iodine in the gut. Response: Thank you for this suggestion. It would have been interesting to explore this aspect. However, in the case of our present study, the assessment of iodised salt and vegetables of the brassica group was out of scope and has been included in the limitation of the study. Comment 5: Clarification about consumption of processed meat. Response: Agree. Here we referred to processed meat as that which has been preserved by smoking, salting, curing, or addition of chemical preservatives. Comment 6: Clearly stipulate factors that are associated with UIC in this section. Factors are not very clear. Response: We agree with this comment and have rewritten the result section to stipulate the factors associated with UIC. Discussion: Comment 1: How were the identified factors influenced iodine status? These have not been adequately articulated in this manuscript. Response: We agree with this comment and have rewritten the discussion section to stipulate the identified factors that influence iodine status. Comment 2: Was the use of iodised salt investigated in the present study? What is the level of consumption among pregnant women? What is the availability and accessibility to iodised salt in the study areas? Response: You have raised an important point here. However, the use of iodised salt (availability and accessibility) was not investigated in this study, and we have included it as part of the study's limitations. Comment 3: Authors indicated some strengths of the study; large sample size; but also identified limitations? One of the limitations was that they did not investigate use of iodised salt in the study area. This is a serious omission considering that iodised salt contributes to iodine intake and therefore UIC at least for a large part of the population. Additionally, there was no control group, which again raises concern over the design of this study. Response: Thank you so much for pointing this out and, we highly appreciate the reviewers’ insightful and helpful comments on our manuscript. It would have been interesting to explore and we have included it in the study's limitations. We will add more information that clarifies the limitation of our study design. Comment 4: Conclusion: It is a repeat of the statement of results and not conclusion. Authors should look at the objectives of the study and provide a concrete conclusion as to whether the objectives were attained and what are the implications to individual women and society in general. Response: Thank you for pointing this out. We agree with this comment and have rewritten the conclusion as suggested."
}
]
}
] | 1
|
https://f1000research.com/articles/10-858
|
https://f1000research.com/articles/12-350/v1
|
30 Mar 23
|
{
"type": "Research Article",
"title": "In-depth assessment of Iraqi physicians' adherence to treatment guidelines for different diseases: a qualitative study",
"authors": [
"Ibrahim Yawer Anwer",
"Mohammed Jamal Yawuz",
"Ali Azeez Al-Jumaili",
"Ibrahim Yawer Anwer",
"Mohammed Jamal Yawuz"
],
"abstract": "Background: In healthcare settings, specialists from different fields may follow the most well-known, reliable, and easy-to-understand medical guidelines. This study aimed to determine Iraqi physicians' adherence to treatment guidelines, to specify which treatment guidelines are utilized for each disease and identify their barriers to follow the guidelines. Methods: This was qualitative study including face-to-face and virtual semi-structured interviews with specialist physicians from different disciplines. The interviews were conducted between December 2021 and May 2022 in Kirkuk province, Iraq. The qualitative data generated through interviews was analyzed using thematic analysis. Result: The study recruited 48 specialists (27 male and 21 female) from seven medical specialties at two large government hospitals. Most physicians (38 /44) revealed that healthcare settings implement treatment guidelines in more than half of cases. American guideline was the most used among the participating physicians. European and British guidelines and textbooks were also used by some specialties. Unfortunately, most (43 out of 47) physicians were unaware of Iraqi treatment guideline. Most seniors often followed the same guidelines for one branch, with little variation in approach based on their experience and flexibility. Almost all participating physicians believed that shortages in treatment (46/47) and investigation/lab materials (45/47) and low patient adherence (44/47) are major barriers to implement the guideline(s). Six out of seven specialties experienced shortage in the essential medications that recommended by the guidelines Conclusions: Most physicians followed well-known international guidelines. Each specialty follows different guidelines relying on the disease. Medication shortage in the public hospitals was the main barrier facing physicians to implement treatment guidelines. Enhancing physician awareness of the Iraqi guidelines should be encouraged. Finally, securing essential medicines in public hospitals is pivotal to adopt evidence-based guidelines effectively.",
"keywords": [
"Guideline",
"Adherence",
"physicians",
"hospitals",
"Iraq",
"qualitative study",
"Interview."
],
"content": "Introduction\n\nAccording to the Institute of Medicine, clinical practice guidelines (CPGs) are statements that are made on purpose to help physicians and patients figure out the best way to treat certain medical conditions.1 Their effective application should enhance the quality of care by reducing treatment discrepancies and incorporating innovations into routine practice. Despite widespread dissemination, the impact of guidelines on physician conduct has been minimal. In general, not much is known about how and why physicians change their practices after learning about a guideline.2\n\nThe agency should evaluate how guidelines, standards, performance evaluations, and review criteria are expected to: 1) improve the health of a substantial number of individuals; 2) decrease clinically significant variations in the processes and services offered by physicians; and 3) decrease clinically relevant variations in the results of health care.3 Private organizations are advancing on multiple fronts in their efforts to set rules. Emerging are some coordinating mechanisms, but significant problems persist, including unexplained discrepancies across guidelines, overlooked topics, lack of follow-up and inadequate public sharing of the data, participants, and techniques used to develop sets of guidelines.3\n\nPhysician adherence is crucial for transforming suggestions into improved outcomes. However, physician’s adherence to guidelines is impeded by numerous obstacles. Regarding physician attitudes, other potential obstacles include disagreement, identity, outcome expectancies, and the inertia of previous practice. Even if a physician has the right knowledge and attitude, outside factors may make it hard for him or her to follow through on recommendations. The factors that commonly influence physicians’ adherence to treatment guidelines The criteria are well-known and consist of (i) the strength of the data that led to the real treatment recommendations, (ii) comfort with the suggestions, (iii) the physician’s acceptance of the suggestions, (iv) the expected influence of a treatment action on the condition, (v) the patient demographic, and (vi) organizational factors such as workload and the comfort of the suggestions.4,5\n\nThe intent of the guidelines was to aid physicians and patients in making proper decisions regarding healthcare such as creating a global strategy for the prevention and control of chronic respiratory diseases, with a focus on developing countries, definition of practices that meet the requirements of many patients in most cases and offering a spectrum of commonly accepted methods for the diagnosis, treatment, and prevention of diseases or conditions; and enhancing coordinate. Talking about a number of well-known ways to diagnose, treat, and prevent certain diseases or conditions; and enhancing coordination between existing government and non-government programs to treat chronic respiratory diseases.3 They are distinct from traditional literature reviews and textbooks by the specific procedures employed in their preparation, which often involve a group of experts (and, increasingly, patients and care givers) who utilize a systematic approach to find and assess the evidence. The experience of the guideline development group is coupled with evidence from secondary research, often in the form of systematic reviews, to produce a set of clinical practice guidelines.3 Additionally, clinical guidelines should be distinguished from protocols, opinions, and alternatives, in which a synthesis of the data reveals a range of feasible interventions and the evidence that supports each one. For example, the American Psychological Association’s empirically supported treatment approach.6 Some CPGs are developed by organizations. Others are produced by regional groupings and are country specific. There is substantial diversity across regional guidelines for a single disease, and as a result, their recommendations are frequently inconsistent. This is largely attributable to the diverse approaches employed to develop these guidelines.7 Therefore, instruments are required to evaluate the quality of guidelines.7\n\nGuidelines for chronic diseases are followed by physician’s worldwide could fall into the following categories: European Society of Cardiology, American Heart Association, American College of Cardiology, Global Initiative to Combat Asthma (GINA), the British Thoracic Society (BTS), the National Institute for Health Care Excellence (NICE) GOLD 2020 is the Global Initiative for Chronic Obstructive Lung Diseases. American Thoracic Society COPD Guidelines pulmonary rehabilitation COPD guidelines. The American Diabetes Association the European Association for Diabetes (EASD). The American Neurological Association (ANA) and the European Urological Association (EAU) are both professional organizations. The Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (NKF KDOQI) The American Rheumatology Association. EULAR is the European Alliance of Rheumatology Associations.\n\nThe British Royal College of Obstetricians and Gynecologists, the American obstetric and gynecological society. The methods of guideline formulation should guarantee that patients treated in accordance with the guidelines will achieve the desired outcomes. This section examines the five steps involved in the creation of an evidence-based guideline. The dissemination, implementation, and assessment of practice guidelines will be covered in the final piece of this series.8\n\nLimited information was available about the adherence of Iraqi physicians to treatment guidelines. The objectives of this study were to determine Iraqi physicians’ adherence to treatment guidelines, to specify which treatment guidelines are utilized for each disease and identify their barriers to follow the guidelines. Participants of both genders were included in this study, and their answers were comparable.9\n\n\nMethods\n\nThematic analyses were performed to analyze interview-generated qualitative data. From the semi-structured interviews, we obtained qualitative data. The participant comments were used to identify and produce themes throughout the qualitative analysis stage. The study team double-checked the comments. For the qualitative phase, an inductive analytic approach (data-driven) and a constructivist paradigm were employed.10 This indicates that we did not rely on a preexisting framework to construct the themes, but instead generated them from the common trends that developed from the participant comments. Each sentence inside the participant’s comments constituted the data item. The qualitative analysis was double checked by peers and debriefed to make sure that the results were accurate and trustworthy.\n\nThe Scientific Committee at the Department of Clinical Pharmacy and the Central Ethical Committee of the College of Pharmacy at Baghdad University reviewed and approved the research proposal including objectives and methodologies on 20th November 2021. Before administering the questionnaire, the researcher described the goal of the study and got each participant’s written consent. The participants were not provided with any incentives.\n\nThis qualitative study consisted of individual interviews with physicians from various specialties (cardiology, rheumatology, gynecology, pediatrics, neurology, and nephrology) who have worked with the treatment guidelines. Nevertheless, the sample size was chosen by the data saturation threshold, a crucial feature of these types of investigations. In other words, data collection ceased when a saturation level was reached and no additional data could be gathered (i.e., new participants were repeating the same previous answers). Specialists completed semi-structured interviews. The study’s stated methodological orientation was thematic analysis. Purposive sampling was used to select participants. To approach participants, face-to-face interviews were used. There were 48 participants in this study. This study includes both male and female specialists, who were selected using a purposive sampling method.9 Two physicians refused to participate because they were not interested.\n\nAlmost all interviews (N = 48) were performed face-to-face at Kirkuk province’s public hospitals. Internists, nephrologists, gynecologists, neurologists, cardiologists, rheumatologists, and pediatricians. The study’s time frame was from December 2021 to May 2022. Each interview lasted 10–15 minutes. Demographic data were used for the sample description.\n\nParticipating in the research were physicians who worked in public hospitals, had experience with guidelines, and one of the following specialties: internal medicine, nephrology, gynecology, neurology, cardiology, rheumatology and pediatrician.\n\nThe exclusion criteria for the study were physicians with specialties not covered in our study branches and other health workers who did not deal with guidelines.\n\nIn order to remove prejudice, participants with hearing, speech, or cognitive impairments that hinder topic understanding were eliminated from the sample.\n\nA purposive sampling method was used to select physicians who work in public hospitals in the province of Kirkuk was taken between December 2021 and May 2022. The physicians were invited in-person to participate in the study. The purposive sampling method was done to identify “individuals who have extensive knowledge of or experience with an interesting phenomenon”.11,12 The researchers employed a snowball method. The term “snowballing” refers to the practice of asking participants to recommend specialists who might be willing to take part in the research and who fit the inclusion criteria. Consequently, the study employed two sampling techniques: purposive and snowball. One researcher conducted in-person interviews during face-to-face hospital meetings. Some participants asked for the interview guide ahead of time so they could Prepare themselves for answers and to save time. The interviews continued until the point of data saturation was achieved. Optional audio recording was available because it could deter potential interviewers from participating. In fact, most physicians refused to record the session. To overcome this limitation, people who rejected the recording for member verification were given handwritten responses (volunteer verification). The author was a male pharmacist with five years of experience and a Bachelor of Science in pharmacy. Before the study began, a good rapport was established with the participants, and they were informed that the author is a master’s student. The interviews were semi-structured and comprised open-ended inquiries. Before conducting interviews, verbal consent was acquired from respondents, which was approved by the ethics board given that the study had no intervention (negligible risk). The interviewees’ information was maintained in confidence. Each interview lasted 10–15 minutes and was conducted in hospitals. Two bilingual authors translated the Arabic sentences (transcripts) into English. Most interviews were performed in English, Arabic, Kurdish, and Turkish languages (mixed languages based on the participant’s English proficiency). Participants were given interview instructions (questions) by the author. No repeated interviews were conducted. Several individuals were interviewed using an audio recorder. Notes taken during and following interviews. Participants did not receive their transcripts, and they did not provide feedback on the findings.\n\nThis study was conducted to evaluate the adherence of Iraqi physicians to medical guidelines for the treatment of various diseases. The interview guide was broken up into two parts. Part-1 included full participant characteristics were gender, occupation, level of education, professional title, area of expertise, years of practice, and workplace. Part-2 consisted of eleven questions posed to specialists in various fields (Table 1). The interview guide was not piloted. The interview began by introducing the researcher and the purpose of the study. The names of participants were not reported.\n\nThe qualitative data obtained from the interviews was analyzed using thematic analysis. During the data’s thematic analysis, Based on participant comments, two authors (AA and IY) discovered and constructed themes. We followed Braun and Clarke’s six phases of thematic analysis, which included acquainting ourselves with the data (comments), generating initial codes, searching for themes, evaluating themes, defining and naming themes, and writing the report.13 As quotations, the completed statements (ideally with examples) were selected. The study team double-checked the transcription. A data-driven inductive analytic technique and a constructivist worldview were employed.11 This means that, rather than relying on a pre-existing framework, we derived the themes from prevalent patterns that emerged from the participant responses. The data was coded with two data codes. The author failed to provide a description of coding trees. No software was utilized in this study. There was consistency between the presented data and the findings. The findings clearly present major and minor themes. Finally, peer verification and debriefing were conducted twice to confirm the findings.\n\n\nResults\n\nThe study recruited 48 specialists (senior physicians) from seven medical specialties (27 male and 21 female) (Internal Medicine, Neurology, Cardiology, Rheumatology, Gynecology, Pediatrics, and Nephrology).14 The specialists were from two largest hospitals in the province of Kirkuk (Azadi Teaching Hospital and Kirkuk General Hospital). Their specialist practice experience ranged from one to 28 years. The specialists’ academic credentials ranged from High Diploma (14) and MSc (7) to board, clinical degree equivalent to a PhD (27) (Table 2).\n\nThe study’s findings revealed multiple themes (Table 3). Specialists partially adhere to international guidelines (mainly American and European); not all physicians adhere to the same guidelines; essential medicines are unavailable; and most of them are unaware of national guidelines.\n\n\n\n➢ 20/44 physicians expected healthcare settings implement treatment guideline in 70% or more of cases\n\n➢ 18 physicians assumed that healthcare settings implement treatment guideline in 50-60% more of cases\n\n➢ 4 physicians assumed that healthcare settings implement treatment guideline in less than 50 of cases\n\n\n\n1. American Diabetic Association (ADA) form DM (9/9 all Internal Medicine)\n\n2. Global initiative for asthma (GINA) for asthma (5 Internal Medicine).\n\n3. NICE or American Heart Association (AHA) guidelines for hypertension (3 Internal Medicine)\n\n\n\n1. American College of Cardiology (ACC) (2/5 cardiologists)\n\n2. American Heart Association (AHA) guidelines (3 cardiologists)\n\n3. ESC European society of cardiology (3 cardiologists)\n\n\n\n1. American College of Rheumatology (ACR) Guideline (all 8 rheumatologists)\n\n2. European Alliance of Association for Rheumatology (EULAR)\n\n\n\n1. Global initiative for asthma (GINA) for asthma (3/7).\n\n2. The WHO for gastroenteritis (GE)(6/7)\n\n3. Nelson textbook of pediatrics (4/7)\n\n\n\n➢ Ease of use.\n\n➢ Based on real world studies.\n\n➢ More applicable in our society.\n\n➢ Updated.\n\n➢ Gives good results/benefits\n\n➢ Worldwide use.\n\n➢ It has been taught in our post-graduate/specialty program.\n\n➢ Required by the MOH\n\n\n\n➢ 18 believed that all/most physicians within the same setting/discipline follow the same guideline.\n\n➢ 17 believed that not all physicians within the same setting/discipline follow the same guideline.\n\n➢ 12 physicians did not know.\n\n\n\n➢ Shortage in treatment and investigation tools, low patient education and compliance (Int 1).\n\n➢ Shortage in investigation tools, and treatment, lack of stroke unit, limited no of MRI, and CT SCAN (Neu 9).\n\n➢ Inadequate medications, investigation and patient follow up and crowded hospitals (Neph2) .\n\n➢ Inadequate medications, investigation, and catheterization equipment, lack of stroke unit, and crowded hospitals. (Neu 2).\n\n➢ Ignorance of people, untrained sub staff, lack of some equipment, and resistance to change (Ped 3).\n\nThe majority of healthcare settings partially implement treatment guidelines.\n\nThe majority of physicians (38/44) revealed that treatment guidelines are implemented in less than half of the cases in healthcare settings.\n\n“Not always, based on available facilities” (Int1)\n\n“Yes, but only by 30-40%” (Int9).\n\nDepending on the disease, each specialty adheres to a different set of guidelines. American guidelines were the most utilized by participating physicians/hospitals. Some specialties also follow European and British guidelines.\n\nFive of seven specializations adhere to American guidelines: the American Diabetic Association (ADA), the American Neurological Association (ANA), the American College of Cardiology (ACC), and the American College of Rheumatology (ACR) (ACR).\n\n“They [American guidelines] are easy for our society, more up-to-date, and taught in our post-graduate education” (int1).\n\nNearly all gynecologists followed the guidelines of the Royal College of Gynecology, while some internists relied on those of the National Institute for Health and Care Excellence (NICE, UK). The vast majority of internists and pediatricians follow the Global Initiative for Asthma (GINA). The majority of pediatricians continue to utilize the Nelson textbook.\n\n“It (American College of Rheumatology) is more reliable, evidence-based, and straightforward to implement” (Rhe2).\n\n“They [GINA for asthma and the WHO for GE] get good results, availability of the drugs suggested by the guidelines, and high family compliance” (Ped4).\n\n“Because it is a textbook, simple, up-to-date, and more reliable\" (Ped6).\n\nThe physicians utilized the same guidelines they learned during their board/postgraduate residency programs. Some cardiologists and rheumatologists adhered to European guidelines.\n\nThe guidelines were put in place for a number of reasons, including their use in clinical settings, their inclusion in postgraduate and specialty programs, and a mandate from the MOH.\n\nThe great majority of participating physicians had little knowledge of Iraqi treatment guidelines.\n\nUnfortunately, the majority of physicians (43 out of 47) were unaware of the Iraqi treatment guidelines.\n\n“I am unaware of [the Iraqi guideline], and I think it is unavailable” (Int7).\n\nThe MOH does not mandate any official guidelines (Int8).\n\n“For GE, yes, but I am unaware of ASHMA” (Ped4 and Ped5).\n\nThe majority of recommended medications were unavailable in public hospitals.\n\nThe necessary medications indicated by the guidelines were in inadequate supply in six out of seven specialties\n\n“The vast majority of [essential medications] are unavailable.” (Int 3,5,9,10,11, neuro5, car2, Rhe1,3,6,7, Gyn1,2,4, Neph3).\n\nMost pediatricians, though, said that needed medicines were easy to find in pediatric hospitals.\n\nYes, the majority of [essential medications] are available (Ped, 1,2,3,4,5,7).\n\nThe majority of hospitals (six out of eight rheumatologists) lacked disease-modifying antirheumatic medicines (DMARDs). Several rheumatologists also said that methotrexate, azathioprine, COX-II selective NSAIDs, and biological medications were not available (Figure 1).\n\nSix neurologists and four out of five cardiologists concurred that anti-thrombolytic medications are in short supply (e.g., actilyse). In addition, the majority of neurologists (four out of six) recognized that their facilities lacked a specialized stroke unit for treating patients with cerebrovascular accidents (CVA) (Figure 2). Flecainide (antiarrhythmic) and Platelet Glycoprotein IIb/III inhibitor (Eptifibatide) were the most frequently missed cardiovascular medications in hospitals (Figure 2).\n\nAll gynecologists encountered a shortage of ovulation-inducing medications (such as clomiphene and letrozole) (Figure 3). The majority of pediatricians and internists reported a shortage of cortisone-plus-short-acting beta2-agonist (SABA)-containing combination asthma inhalers (Figure 3 and 4). In addition, seven out of ten internal medicine doctors reported a shortage of innovative oral hypoglycemic medicines (Figure 4).\n\nThere are no ovulation-stimulating drugs (like Letrozole and clomiphene) at the hospital (all 6 gynecologists: Gyn 1,2,3,4,5,6).\n\nThere is a shortage of inhalers containing both SABA and cortisone (Ped 1,2,4,5,7).\n\nSeveral barriers restrict physicians from implementing the guidelines in public healthcare settings.\n\nNearly all participating physicians viewed shortages of treatment (46/47) and investigation/lab materials (45/47) as well as low patient adherence (44/47) as important barriers to implementing the guideline(s) (Figure 5).\n\n“Lack of investigational tools and treatment, absence of a stroke unit, restricted availability of MRI and CT scans” (Neu 9).\n\nThere isn’t enough medicine, testing, and catheterization equipment; there isn’t a stroke center; and hospitals are too full (Neu 2).\n\n“Ignorance of individuals, untrained substaff, equipment shortages, and resistance to change” (Ped 3).\n\nMost physicians agreed that there are two main problems with putting guidelines into practice in private settings: high prescription costs (47/47), and it’s hard to keep track of patients (21/47) (Figure 6).\n\n“High costs and difficult patient follow-up” (Int 1,2,3,5, Rheu 8, Gyn 3,5, Ped 2).\n\n\nDiscussion\n\nUsing medical guidelines to cover nearly all specialties was one of the study’s strengths, and the majority of participants were well-regarded professionals having considerable experience. The study’s participants were physicians with knowledge or expertise of medical guidelines; thus, the findings may not be representative of all physicians.15\n\nIn fact, the majority of specialists had good expertise with guidelines in their respective branches, and they stated as much (they follow new updates in the guidelines to apply new recommendations to patients in order to get the best results in their treatment approach). In this study, the author observed that specialists almost always adhere to the most well-known and globally dependable guidelines due to their postgraduate studies based on these guidelines, as well as because these guidelines are simple and applicable to our society and provide the greatest benefits. Unfortunately, seniors did not follow all of the guidelines’ recommendations due to the barriers and other reasons that have already been mentioned. Specialists’ approaches to treatment were unaffected by gender since they adhered to the same guidelines.9 Several studies analyzed the primary information sources on antibiotics utilized by physicians. The majority of physicians in the studies were familiar with antibiotic prescribing recommendations, although some did not follow them. In Sudan, for instance, only 32.6% of physicians resorted to the Sudan National Formulary or the British National Formulary while making decisions, while the remainder did not consult any reference source.16\n\nAccording to the majority of specialists, there are no Iraqi guidelines that cover the majority of diseases in their respective branches, which were covered in this study. There is no established central organization in Iraq that develops guidelines for the majority of diseases treated in public health care settings. Also, they tell the Ministry of Health and medical associations to make Iraqi guidelines that are more useful, adaptable to our community, and in line with the facilities in our country.\n\nThere were good connections and discussions between specialists and physicians (permanents and rotators) regarding diseases and guidelines, whereas there were few discussions with pharmacists regarding guidelines. The low physician acceptance of pharmacist recommendations suggests that physicians may underestimate the risk of drug-drug interactions. In fact, some of these contacts were classified as grave mistakes.17\n\nAccording to their experience with patients and diseases and the results obtained with these selections, the majority of seniors in one branch followed the same guidelines with minor variations in details, such as (some seniors chose valsartan while others chose candesartan from the same ARBs group). According to their board/post-residency training program, their experiences with patients, and the results they obtained from implementing these guidelines, the majority of specialists followed guidelines, whereas a minority followed textbooks. Iraqi physicians rely on the most well-known and reliable guidelines in the world, such as the American guidelines, which were utilized most frequently by the participating physicians and hospitals. Some specialties also follow European and British recommendations.\n\nThe majority of medications and investigational tools that aid physicians in disease diagnosis were scarce or unavailable in Iraqi public health care settings. The shortage of life-saving treatments and the absence of important centers such as the stroke unit in all hospitals in the province make it difficult for specialists to diagnose and treat such cases, forcing them to refer patients to the private sector or recommend medication and lab tests from outside (private settings).\n\nRegarding the implementation of guidelines for the treatment of various diseases, physicians faced significant barriers. Major barriers were the unavailability or shortage of medications; investigational tools (laboratory tests, x-rays, MRIs, CT scans, etc.); patients’ education; adherence; and physician follow-up. Incapability to properly answer questions on the content of the guidelines, as well as self-reported unfamiliarity with the material, constituted a lack of familiarity. About two-thirds of the physicians were willing to prescribe low-cost medications, but only about half of them reported prescribing generic medications to their patients. This indicates a discrepancy between physician intent and prescribing behavior. Again, the risk of therapeutic failure is a key concern for physicians when they prescribe generic medications, especially in the private sector.18 Lack of cognition Due to the ever-increasing volume of research, it is challenging for a physician to be aware of and properly implement all applicable guidelines. Lack of acquaintance Awareness does not necessarily imply familiarity with and the ability to successfully apply guidelines.19 Iraqi physicians favored biosimilar medications licensed by the U.S. FDA and the European Medicines Agency (EMA). This is likely due to their increased confidence in the stringent restrictions of the U.S. FDA and the EMA about the approval of safe and effective biosimilars. On the other hand, the fact that biosimilar medicines made in neighboring countries and brought into Iraq may not have these international approval certifications makes it much harder for physicians to accept them.20\n\nAbsence of Agreement Doctors may disagree with a particular guideline or the notion of recommendations. In general, although physicians frequently indicate disagreement when questioned about guidelines theory, this and previous analyses indicate that disagreement is less prevalent when physicians are asked about specific guidelines.21\n\nLack of outcome expectations the expectation that a specific consequence will result from a particular behavior. If physicians perceive that a recommendation would not improve patient outcomes, they will be less inclined to follow it.22\n\nBarriers to the use of EBM such as individual obstacles, including EBM skills (79.0%) and time (61.9%), were identified the most frequently. The fact that societal circumstances and legislation restrict the usefulness of evidence (55.2%), that there is no control over the practice of evidence (45.7%), and that the evidence is too difficult or theoretical to apply to practice (47.6%) were also frequently cited as impediments.23 Patients may be resistant to or think guideline recommendations are unnecessary. Additionally, a patient may find the recommendation disrespectful or embarrassing. Conformity to practice guidelines “may necessitate non-physician-controlled adjustments, such as the procurement of new resources or facilities”.24,25 For instance, the lack of a 24-hour anesthesiologist may hinder the ability of a physician to adhere to advice intended to reduce the rate of elective cesarean births. Many of the things that more than 10% of respondents said were barriers, like not having a reminder system, not having enough counseling materials, not having enough staff or consultant support, getting paid too little, having to pay more for practice costs, and having more liability, may be out of the doctors’ hands.25 In advance, the barriers to guideline implementation and adherence in any given instance must be analyzed so that methods that are suited to the unique situation and target groups can be established. To be effective in influencing physicians’ behavior, the plan must involve a variety of intervention types and target physicians’ knowledge and attitudes.26\n\nThe majority of participating physicians rely on and adhere to guidelines’ recommendations and instructions for a variety of reasons, including that they are simple to use, based on real-world studies, more applicable in our society, updated, provide good results/benefits, are used globally, and have been taught in our post-graduate/specialty program. All of these things make older people rely on rules and follow each update.\n\nThe way guideline recommendations were used varied a lot from branch to branch and from ward to ward, depending on the hospital facilities that were available. Due to the many barriers that were pointed out in this study, most seniors said that less than 70% of recommendations were followed. However, some seniors said that more than 70% of recommendations were followed in some cases and diseases.\n\nThe majority of specialists followed the same guidelines Across both the private and public sectors. In the private sector, some physicians use their experience or a mix of guidelines. However, the large number of facilities available in the private sector gives physicians a lot of options and flexibility in how they treat their patients.\n\nThe study was limited to one province and as other qualitative studies, the findings may not be generalizable to all provinces. The interview guide was not piloted.\n\n\nConclusions\n\nIn our public healthcare settings, specialists from seven fields utilized the most well-known and universally accepted guidelines. The majority of physicians (38/44) revealed that healthcare settings implement treatment guidelines in more than half of cases. American guideline was the most commonly used among the participating physicians. European and British guidelines and textbooks were also used by some specialties. Unfortunately, most physicians were unaware of Iraqi treatment guideline. Most senior physicians often followed the same guidelines for one branch, with little variation in approach based on their experience and flexibility. Almost all participating physicians believed that shortages in treatment and investigation/lab materials and low patient adherence are major barriers to implement the guideline(s). Six out of seven specialties experienced shortage in the essential medications that recommended by the guidelines. Enhancing physician awareness of the Iraqi guidelines should be encouraged. Finally, securing essential medicines in public hospitals is pivotal to adopt evidence-based guidelines effectively.",
"appendix": "Data availability\n\nFigshare: In-depth Assessment of Iraqi physicians’ Adherence to Treatment Guidelines for Different Diseases: A Qualitative Study. https://doi.org/10.6084/m9.figshare.21624327.v1. 14\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 would like to thank all the participating healthcare providers in Kirkuk General hospital and Azadi Teaching hospital in Kirkuk province, Iraq for sharing their experience.\n\n\nReferences\n\nKN, editor. Clinical Practice Guidelines: Directions for a New Program. National Academies Press. Institute of Medicine (US) Committee to Advise the Public Health Service on Clinical Practice Guidelines;1990. Marilyn J. Field, Kathleen N. Lohr Washington (DC): National Academies Press (US).\n\nGundersen L: The effect of clinical practice guidelines on variations in care. Ann. Intern. Med. 2000; 133: 317–318. 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Englewood Cliffs, NJ:Prentice-Hall Inc;1986.\n\nHeselmans A, Donceel P, Aertgeerts B, et al.: The attitude of Belgian social insurance physicians towards evidence-based practice and clinical practice guidelines. BMC. Fam. Pract. 2009; 10: 64. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWoo B, Woo B, Cook EF, et al.: Screening procedures in the asymptomatic adult: comparison of physicians’ recommendations, patients’ desires, published guidelines, and act practice. JAMA. 1985; 254: 1480–1484. Publisher Full Text\n\nKosecoff J, Kanouse DE, Rogers WH, et al.: Effects of the National Institutes of Health Consensus Development Program on physician practice. JAMA. 1987; 258: 2709–2713.\n\nFischer F, Lange K, Klose K, et al.: Barriers and Strategies in Guideline Implementation—A Scoping Review. Healthcare. 2016; 4: 36. PubMed Abstract | Publisher Full Text | Free Full Text"
}
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[
{
"id": "205712",
"date": "13 Oct 2023",
"name": "Alison H Howie",
"expertise": [
"Reviewer Expertise Epidemiology",
"physician adherence to guideline recommendations"
],
"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 paper describes a qualitative study of physician adherence to guideline recommendations within hospitals in Iraq. I believe the study was well-conducted and is an important addition to the literature, however, I have several concerns that I believe must be addressed before publication, as described below.\n\nAbstract:\nYou say there were 48 participants but the results use 44 or 47 as the denominator. Could you include one sentence acknowledging/explaining the missing data?\n\nWhat is meant by “branch”? Is it synonymous with specialty? This is not a well-known term; I suggest re-wording or clarifying.\n\nIntroduction:\n1. I suggest removing “on purpose” from the first sentence.\n2. Several sentences make claims that are not referenced. I suggest reviewing the introduction for these sentences, including:\n\n“Despite widespread dissemination, the impact of guidelines on physician conduct has been minimal.” (para 1) “Private organizations are advancing on multiple fronts in their efforts to set rules.” (para 2) “Regarding physician attitudes, other potential obstacles include disagreement, identity, outcome expectancies, and the inertia of previous practice.” (para 3)\n3. What is meant by “the agency” in the first sentence of the second paragraph? I suggest elaborating/clarifying.\n4. The following sentence is unfinished: “The factors that commonly influence physicians’ adherence to treatment guidelines”\n5. The fourth paragraph sounds like it’s referring to a specific guideline regarding respiratory diseases, but it is not clear which. Suggest explicitly mentioning and referencing the guideline. It also introduces the idea that guidelines are meant for physicians and patients, but the rest of the introduction focuses on physicians. Adding patients here without explanation feels out of place.\n6. The second sentence in the fourth paragraph repeats what is already said in the previous sentence - suggest merging the two sentences.\n\n7. Paragraphs 5 and 6 could use some editing. There are unfinished sentences and perhaps too many examples. Suggest only including a handful of examples (with references).\n\n8. The last sentence of the introduction, “Participants of both genders were included in this study, and their answers were comparable.” belongs in the results/discussion.\n\nMethods:\n\nOverall comment: several sentences are repeated in multiple sections of the methods, and several sentences include results from the study and do not belong in the methods. The whole methods section needs to be reviewed carefully and duplicate sentences and results-based sentences need to be removed.\n\nThe first paragraph about the analysis of the data is misplaced. Suggest moving it to the thematic analysis section at the end of methods and removing duplicate sentences, e.g., “Thematic analyses were performed to analyze interview-generated qualitative data.”\n\nIn the ethical approval section, it says, “before administering the questionnaire”. This is the first mention of a questionnaire. Was it a mixed-methods study? If not, suggest re-wording this as it may confuse readers.\n\nAny mention of results does not belong in the methods, including the number of participants in the study. The following sentences should be removed as they are repeated in the results:\n\n“There were 48 participants in this study. This study includes both male and female specialists, who were selected using a purposive sampling method. Two physicians refused to participate because they were not interested.” “Almost all interviews (N = 48) were performed face-to-face at Kirkuk province’s public hospitals.”\nFor this one, you could just say “Interviews were performed face-to-face at Kirkuk province’s public hospitals” without including the number of participants.\n\n“In fact, most physicians refused to record the session.” “Most interviews were performed in English, Arabic, Kurdish, and Turkish languages (mixed languages based on the participant’s English proficiency).”\n5. In the settings section, suggest removing the second sentence (“Internists, nephrologists, gynecologists, neurologists, cardiologists, rheumatologists, and pediatricians.”) as it is unfinished and repeated in the next section (Eligibility).\n6. I believe the following sentence should use the term “interviewee” instead of “interviewer”: “Optional audio recording was available because it could deter potential interviewers from participating.”\n7. The following sentences are conflicting and also should be in the results section: “In fact, most physicians refused to record the session.” and “Several individuals were interviewed using an audio recorder.”\n8. Missing a word from the following sentence, “Notes taken during and following interviews.” I believe it should say “Notes were taken during and following interviews.”\n9. You explain that participants who refused to record were given a handwritten page to fill out. It is unclear how these data were incorporated into the analysis. In the thematic analysis section, you just talk about transcripts. How was the other data used?\nResults:\n1. Overall comment: the results are heavily focused on quantitative findings - reporting the number of participants whose responses fell under each theme when the purpose is to conduct a qualitative analysis. I’m not sure that all of these numbers belong to the results of a qualitative analysis.\n\n2. Including gender information in the first sentence is out of place. Suggest including a separate sentence for gender.\n\n3. Suggest including the mean number of years of experience in addition to the range.\n4. You say there were 48 participants, but several results use other numbers as denominators (i.e., 44). Please explain the reason for missing data (e.g., did you run out of time to ask some participants some of the questions? Did they refuse to answer some?).\n\n5. Suggest defining “MOH”\n6. You include direct quotations and reference multiple participants for some of them (e.g., “The vast majority of [essential medications] are unavailable.” (Int 3,5,9,10,11, neuro5, car2, Rhe1,3,6,7, Gyn1,2,4, Neph3).” I find it hard to believe that all these participants said the same thing. I believe only the interviewee who said the quote should be named.\n\n7. Sometimes quotation marks are used to indicate a participant's direct quote, other times they are not. The results need to be carefully reviewed for consistency here.\n\nDiscussion:\n1. A lot of information is repeated from the results. The discussion should be an interpretation of the findings at large and a comparison to other studies in the literature. The discussion needs to be reviewed and edited to provide an interpretation of the results.\n2. In the section entitled, “Numerous barriers impeded the implementation of the guidelines by physicians in public hospitals”, you mention “patient education” for the first time. What is meant by this? Avoid introducing new findings in the discussion that were not mentioned in the results.\n\n3. I don’t know what is meant by the following sentence, “All of these things make older people rely on rules and follow each update.” Suggest re-wording or elaborating on this point.\n4. Suggest adding a “Limitations” section at the end of the discussion (there are currently two sentences that refer to limitations within the “Follow the recommendations of the guidelines in both public and private settings” section.\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? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12173",
"date": "22 Aug 2024",
"name": "Ali Azeez Al-Jumaili",
"role": "Author Response",
"response": "This paper describes a qualitative study of physician adherence to guideline recommendations within hospitals in Iraq. I believe the study was well-conducted and is an important addition to the literature, however, I have several concerns that I believe must be addressed before publication, as described below. The authors would thank the reviewer (Dr. Alison H Howie ) for her valuable comments to enhance the quality of the manuscript. Abstract: You say there were 48 participants but the results use 44 or 47 as the denominator. Could you include one sentence acknowledging/explaining the missing data? - Agree with reviewer, the number of participants was 48, so we fixed the numbers in the denominator. What is meant by “branch”? Is it synonymous with specialty? This is not a well-known term; I suggest re-wording or clarifying. - Yes, branch is used in Iraq. However, we replaced it with specialty instead per the reviewer request. Introduction: 1. I suggest removing “on purpose” from the first sentence. - Removed per the reviewer request. 2. Several sentences make claims that are not referenced. I suggest reviewing the introduction for these sentences, including: “Despite widespread dissemination, the impact of guidelines on physician conduct has been minimal.” (para 1) “Private organizations are advancing on multiple fronts in their efforts to set rules.” (para 2) “Regarding physician attitudes, other potential obstacles include disagreement, identity, outcome expectancies, and the inertia of previous practice.” (para 3) - Reviewed. 3. What is meant by “the agency” in the first sentence of the second paragraph? I suggest elaborating/clarifying. - Agency refers to the “Agency for Healthcare Research and Quality\" (AHRQ)”. We fixed it. 4. The following sentence is unfinished: “The factors that commonly influence physicians’ adherence to treatment guidelines” - Sorry, we fixed it. 5. The fourth paragraph sounds like it’s referring to a specific guideline regarding respiratory diseases, but it is not clear which. Suggest explicitly mentioning and referencing the guideline. It also introduces the idea that guidelines are meant for physicians and patients, but the rest of the introduction focuses on physicians. Adding patients here without explanation feels out of place. Removed the patients per the reviewer request. 6. The second sentence in the fourth paragraph repeats what is already said in the previous sentence - suggest merging the two sentences. Deleted the 2nd sentence to avoid duplication. 7. Paragraphs 5 and 6 could use some editing. There are unfinished sentences and perhaps too many examples. Suggest only including a handful of examples (with references). Agree with the reviewer, so we fixed and shortened them to the following: Guidelines for chronic diseases are followed by physician’s worldwide could fall into the following categories: European Society of Cardiology, American Heart Association, American College of Cardiology, Global Initiative to Combat Asthma (GINA), the American Diabetes, the American Neurological Association (ANA), the European Urological Association (EAU) , the American Rheumatology Association and the European Alliance of Rheumatology Associations (EULAR) and the British Royal College of Obstetricians and Gynecologists. 8. The last sentence of the introduction, “Participants of both genders were included in this study, and their answers were comparable.” belongs in the results/discussion. Agree, the last sentence was deleted. Methods: Overall comment: several sentences are repeated in multiple sections of the methods, and several sentences include results from the study and do not belong in the methods. The whole methods section needs to be reviewed carefully and duplicate sentences and results-based sentences need to be removed. - The method section has been revised per the reviewer request. The first paragraph about the analysis of the data is misplaced. Suggest moving it to the thematic analysis section at the end of methods and removing duplicate sentences, e.g., “Thematic analyses were performed to analyze interview-generated qualitative data.” - Agree with the reviewer, we moved the first section to the thematic analysis section. In the ethical approval section, it says, “before administering the questionnaire”. This is the first mention of a questionnaire. Was it a mixed-methods study? If not, suggest re-wording this as it may confuse readers. - Revised to “before administering the interview questions”. Any mention of results does not belong in the methods, including the number of participants in the study. The following sentences should be removed as they are repeated in the results: “There were 48 participants in this study. This study includes both male and female specialists, who were selected using a purposive sampling method. Two physicians refused to participate because they were not interested.” “Almost all interviews (N = 48) were performed face-to-face at Kirkuk province’s public hospitals.” For this one, you could just say “Interviews were performed face-to-face at Kirkuk province’s public hospitals” without including the number of participants. “In fact, most physicians refused to record the session.” “Most interviews were performed in English, Arabic, Kurdish, and Turkish languages (mixed languages based on the participant’s English proficiency).” We removed the results from the method section per the reviewer request. 5. In the settings section, suggest removing the second sentence (“Internists, nephrologists, gynecologists, neurologists, cardiologists, rheumatologists, and pediatricians.”) as it is unfinished and repeated in the next section (Eligibility). Removed. 6. I believe the following sentence should use the term “interviewee” instead of “interviewer”: “Optional audio recording was available because it could deter potential interviewers from participating.” Agree, interviewee. 7. The following sentences are conflicting and also should be in the results section: “In fact, most physicians refused to record the session.” and “Several individuals were interviewed using an audio recorder.” Revised. 8. Missing a word from the following sentence, “Notes taken during and following interviews.” I believe it should say “Notes were taken during and following interviews.” Done. 9. You explain that participants who refused to record were given a handwritten page to fill out. It is unclear how these data were incorporated into the analysis. In the thematic analysis section, you just talk about transcripts. How was the other data used? Revised to “ in addition to notes taking by the interviewer during the interview”. It means we had transcripts including both hand-written from the interviewee and notes from the interviewer. Results: 1. Overall comment: the results are heavily focused on quantitative findings - reporting the number of participants whose responses fell under each theme when the purpose is to conduct a qualitative analysis. I’m not sure that all of these numbers belong to the results of a qualitative analysis. We tried to put number of participants who mentioned the same theme and subtheme, so the readers would understand the portion of agreement on each theme. 2. Including gender information in the first sentence is out of place. Suggest including a separate sentence for gender. Done. 3. Suggest including the mean number of years of experience in addition to the range. The mean of experience year was added. 4. You say there were 48 participants, but several results use other numbers as denominators (i.e., 44). Please explain the reason for missing data (e.g., did you run out of time to ask some participants some of the questions? Did they refuse to answer some?). We fixed these denominators to be 48. 5. Suggest defining “MOH” The Iraqi Ministry of Health 6. You include direct quotations and reference multiple participants for some of them (e.g., “The vast majority of [essential medications] are unavailable.” (Int 3,5,9,10,11, neuro5, car2, Rhe1,3,6,7, Gyn1,2,4, Neph3).” I find it hard to believe that all these participants said the same thing. I believe only the interviewee who said the quote should be named. They used very similar words. Per the reviewer request, we kept two participant pseudo names who said exactly the same answer. 7. Sometimes quotation marks are used to indicate a participant's direct quote, other times they are not. The results need to be carefully reviewed for consistency here. Done Discussion: 1. A lot of information is repeated from the results. The discussion should be an interpretation of the findings at large and a comparison to other studies in the literature. The discussion needs to be reviewed and edited to provide an interpretation of the results. The discussion has been revised per the reviewer request. 2. In the section entitled, “Numerous barriers impeded the implementation of the guidelines by physicians in public hospitals”, you mention “patient education” for the first time. What is meant by this? Avoid introducing new findings in the discussion that were not mentioned in the results. Agree. It is done. 3. I don’t know what is meant by the following sentence, “All of these things make older people rely on rules and follow each update.” Suggest re-wording or elaborating on this point. Removed to avoid redundancy. 4. Suggest adding a “Limitations” section at the end of the discussion (there are currently two sentences that refer to limitations within the “Follow the recommendations of the guidelines in both public and private settings” section. Done We highly appreciate the reviewer’s valuable comments to enhance the quality of our manuscript. Best regards, Ali Azeez Al-Jumaili, MPH, PhD Corresponding author"
}
]
},
{
"id": "176786",
"date": "11 Sep 2024",
"name": "Omar Q.B. Allela",
"expertise": [
"Reviewer Expertise Clinical pharmacy"
],
"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\nPhysician adherence is very important, so this article will add a good idea and clear picture for this important problem (non-adherence to guideline). But also so important to add a quantitative study to be completed study. Regarding conclusion, need to list more points to apply for the area in future.\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/12-350
|
https://f1000research.com/articles/13-952/v1
|
22 Aug 24
|
{
"type": "Research Article",
"title": "Mechanisms of Selected Cassipourea Metabolites for Melasma Treatment: Network Pharmacology and Molecular Dynamics Study",
"authors": [
"Nomakhosi Mpofana",
"Christina Peter",
"Halimat Yusuf Lukman",
"Mokgadi Ursula Makgobole",
"Ncoza Cordelia Dlova",
"Nceba Gqaleni",
"Ahmed Hussein",
"Saheed Sabiu",
"Christina Peter",
"Halimat Yusuf Lukman",
"Mokgadi Ursula Makgobole",
"Ncoza Cordelia Dlova",
"Nceba Gqaleni",
"Ahmed Hussein",
"Saheed Sabiu"
],
"abstract": "Background Melasma is a common dyschromia, mainly found in women with darker skin types. Although asymptomatic, melasma significantly impacts patients’ quality of life. Due to this complex pathogenesis, melasma is difficult to treat. Plant and plant-derived products have been explored as alternatives for the treatment of melasma.\n\nMethods This study utilized network pharmacology coupled with molecular docking and molecular dynamics simulations to investigate the molecular mechanisms of three selected Cassipourea metabolites in the treatment of melasma.\n\nResults Of the 202 genes obtained from the 14 profiled metabolites, only PTGS2, TYR, ESR2, and ESR1 were common among metabolites and targets implicated in melasma. From this, The gene ontology highlighted the intracellular steroid hormone receptor, signalling pathway, macromolecular complex, and estrogen receptor activity as the top enriched functional annotations, while the KEGG pathway analysis identified five signalling pathways, from which the prolactin signalling pathway, endocrine resistance, and estrogen signalling pathway were implicated in the pathogenesis of melasma. These pathways were further connected by their linkage to ESR2 and ESR1., Of all Cassipourea metabolites and standards, with afzelechin having the highest docking score for both gens. Further binding interaction analysis showed that ESR2-bound tamoxifen had the highest binding free energy of -47.68 kcal/mol, however, among the interacting Cassipourea metabolites, sitosterol-glycoside exhibited the highest negative binding affinity for both ESR2 (-40.50 kcal/mol) and ESR1 (-78.97 kcal/mol) over 150 ns simulation, suggesting its potential as a dual modulator. Altogether, the metabolites presented remarkable binding stability and thermodynamic compactness with the apo-genes.\n\nConclusion The finding that the selected Cassipourea metabolites are associated with the genes and enzymes implicated in melasma pathogenesis, together with their significant binding effects on the enriched genes, suggests their regulatory potential on the profiled targets and, consequently, in the treatment of melasma.",
"keywords": [
"melasma",
"Cassipourea species",
"Network pharmacology",
"Molecular dynamics simulation",
"Signalling pathways"
],
"content": "1. Introduction\n\nThe skin is the largest organ in the human body. It forms a significant anatomical barrier between internal and external environments.1 The body is continuously exposed to various physical and chemical exogenous polluting substances.2 Ultraviolet radiation (UVR) from excessive sun exposure is the primary exogenous factor that harms the skin. This process has various harmful effects on the skin as it alters the composition of the skin, causing elastic fiber accumulation, collagen reduction, and degeneration leading to wrinkles, sagging, and glycosaminoglycan deposition, resulting in premature aging, known as photoaging.3 Moreover, overexposure to ultraviolet (UV) rays stimulates melanin synthesis owing to the rapid proliferation of melanocytes. Furthermore; to stimulated melanin synthesis, excessive exposure to sunlight, especially UVA and UVB, causes overexpression of reactive oxygen species (ROS) that harm lipids, proteins, and deoxyribonucleic acids.4\n\nMelanin is produced in the epidermis of the skin via a pathway known as melanogenesis, with tyrosinase playing a key role as the rate-limiting enzyme.5 The enzyme catalyzes three steps in melanin biosynthesis: hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA), oxidation of DOPA to DOPA quinone, and conversion of 5,6-dihydroxyindole to indolequinone.3,6 Thus, tyrosinase is the primary target for determining skin-lightening agents for cosmetic applications or skin lightening.5\n\nWhile melanin shields the skin from UV radiation, excessive production can result in dermatological hyperpigmentation of the skin in clinical conditions such as dark spots, freckles, melasma, solar lentigo, linea nigra, and post-inflammatory hyperpigmentation (PIH), which can affect the appearance of the skin.7 Melasma is a common dermatological condition characterized by hyperpigmentation (light brown or dark brown), flaky or reticular patches, and macules that appear on the facial skin, and much less often on the neck and forearms. This condition primarily affects adult females, especially those with darker skin phototypes (Fitzpatrick skin phototypes III-VI).8,9 Although common to females, men are also affected; the incidence of melasma is estimated at 1% worldwide; however, it varies between 8.8-50% of at-risk populations.10,11 The pathogenesis of melasma is complex, as it is linked to melanocytes, keratin-forming cells, endothelial cells, fibroblasts, and alterations in the basement membrane.12,13 Visible light and UV exposure, hormonal changes, and genetic predisposition have all been linked to the onset of melasma.12–14 Melasma can also be caused by various factors such as the use of photosensitizing medication, thyroid diseases, ovarian tumors, hepatopathies, parasitic infestation, certain foods, and stress.9 Thyroid dysfunction, menstrual cycle irregularities, and insulin resistance which may also be caused by hormonal imbalance, have been linked to the diagnosis of melasma.9,14\n\nAlthough not life-threatening, being a facial disorder, melasma is disfiguring, and as such, impacts patients’ lives and psychological well-being, potentially leading to anxiety, depression, and other disorders.12–15 Owing to this complex pathogenesis, melasma is difficult to treat. Currently, there is no cure or standardized treatment for melasma. Hydroquinone is a popular skin-whitening agent that inhibits tyrosinase. However, it is not suitable for all skin types, and prolonged and unsupervised use can cause undesirable side effects such as dermatitis, edema, allergic reactions, and ochronosis.15,16 Common treatments include sun protection, topical creams, such as niacinamide, vitamins A and C, oral medications, chemical peels, laser and light therapy, tranexamic acid, and microneedling. However, these treatments are prone to chemical irritation, inflammatory reactions, and hyperpigmentation. Other disadvantages include the possibility of recurrence and unpredictable efficacy.12–15\n\nPatients often prefer the use of complementary and alternative medicines to supplement or replace traditional treatments, licorice extract, arbutin, and kojic acid are among the many tyrosinase inhibitors used in skin-lightening treatments.6,15 Additionally, tyrosinase inhibitors from phyto-molecules are equally valuable for scavenging ROS, which cause skin damage from excessive sun exposure.5 Since ancient times, medicinal plants have been used as therapeutic agents, dating back to 4000-5000 BC.17 The biological activities of plants are unique to specific species or groups, which supports the idea that a plant’s secondary metabolites are taxonomically distinct.18 Screening of such secondary metabolites as active compounds from plants has led to the invention of a drug discovery process in pharmaceutical science for isolating new natural drugs with efficient protection and treatment roles against various diseases.18\n\nStudies have explored natural products that inhibit UV-induced ROS, suppress enzymes, and reduce melanin formation as potential alternatives to current treatments have been conducted. This strategic shift is due to the adverse effects of synthetic agents.19 Phytocompounds such as aloesin, arbutin, licorice, hesperidin, gentisic acid, flavonoids, niacinamide, polyphenols, and yeast derivatives have demonstrated great potential to inhibit melanogenesis without harming melanocytes.4,18 Topical botanicals are becoming increasingly popular for skin care because of their perceived safety, low side effects, formulation stability, efficacy, cost-effectiveness, and quick metabolism when applied to the skin compared with conventional treatments.12,17,20 According to ethnobotanical literature, topical application is the most commonly used mode of application because it guarantees direct and immediate interaction of specific botanical compounds with the site of action.21–23\n\nRecently, three Cassipourea species (Cassipourea flanaganii, Cassipourea malosana, and Cassipourea gummiflua Tul. Verticillata) have been reported to be used for skin lightening by women in rural areas in the Eastern Cape and Kwa Zulu-Natal provinces of South Africa.20 Although common names of the species are often used interchangeably by the rural community, the phytochemical comparison showed that each species is distinct, but they share skin-lightening characteristics. All three plants have been demonstrated to be effective and safe for use as topical skin lighteners, with no side effects.17,22–24\n\nIn this context, the biological activities of the three Cassipourea species were systematically analyzed for their potential molecular mechanisms in the treatment of melasma using network pharmacology. Network pharmacology is an emerging science that examines the “compound-protein/gene-disease” system, thus, it is an effective measure for describing the intricacy of biological systems, drugs, and diseases from a network-based context.19,25 However, to gain further insight into the binding interaction and stability of the metabolites and hub targets, molecular docking and dynamics simulations were conducted.\n\n\n2. Methods\n\nActive compounds from the three Cassipourea species screened through Chromatography-Mass Spectrometry (LC-MS/MS) analysis in the negative mode were used to generate a library of compounds for Cassipourea. The LCMS/MS analysis detected twenty-four compounds from various chemical classes, including fatty acids, steroids, di- and triterpenoids, flavonoids, and phenolic acids (https://doi.org/10.6084/m9.figshare.26418361.v1) (accessed on 01 August 2024). Eighteen compounds were tentatively identified.20 The compounds were identified based on their structure and molecular mass, which shared similarities with known substances (https://doi.org/10.6084/m9.figshare.26418361.v1) (accessed on 01 August 2024). This was validated further with previous reports, characteristic fragmentation patterns, and data from a large bank and the SciFinder database.\n\nThe metabolites of the Cassipourea species were evaluated using Lipinski’s rule of five (Ro5) for drug-likeness properties of the metabolites.26 The SwissADME server (http://www.swissadme.ch/; accessed April 01, 2024) was used to predict the absorption, distribution, metabolism, and excretion properties of metabolites.27\n\nThe metabolite target genes were mined from two independent databases. Genes related to Cassipourea metabolites, whose SMILES were available on PubChem (Afzelechin, azelaic acid, cassipourol, chlorogenic acid, chrysin 8-C glucoside, decahydroretinol, emodin 6,8 dimethyl ether, hexose, isorhamnetin-3-O-rhamnoside, lupeol, lyoniside, methyl linoleate, sitosterol-glycoside and tricin) were identified from the Swiss Target Prediction (STP) database (http://www.swisstargetprediction.ch/) (accessed April 01, 2024) using the Simplified Molecular Input Line Entry System (SMILES) retrieved from PubChem (https://pubchem.ncbi.nlm.nih.gov/) (accessed April 01, 2024). Genes related to melasma were acquired from the Online Mendelian Inheritance in Man (OMIM) database (https://www.omim.org/) (accessed on April 01, 2024) and the GeneCards database (https://www.genecards.org/) (accessed April 01, 2024). The Venny 2.1.0 (https://bioinfogp.cnb.csic.es/tools/venny/) tool was used to identify and characterize intersecting target genes28 between Cassipourea metabolites and melasma.29\n\nThe Search Tool for the Retrieval of Interacting Genes (STRING) database (https://string-db.org/) (accessed April 01, 2024) was used to construct a PPI network.30 The parameters for the analysis were set to Homo sapiens with a confidence level of < 0.4, followed by the input of common target genes between metabolites and melasma. The PPI network was then classified using Cytoscape v3.8.2.28 A degree algorithm was used to identify key genes in the network (Equation 1).31\n\nTo illustrate the roles of the identified common targets in biological processes (BP), cellular components (CC), and molecular function (MF), gene ontology was conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool (https://david.ncifcrf.gov/tools.jsp),32 with search parameters fixed to Homo sapiens. The GO and KEGG enrichment pathway analysis plots were generated using SRPlot (http://www.bioinformatics.com.cn/en), and from the KEGG pathway enrichment, the most significant pathway was selected based on the lowest false discovery rate (FDR).33,34\n\nThe PCT comprising melasma-related signaling pathways, their interacting genes, and metabolites were constructed using the Cytomerger plugin in Cytoscape software v3.9.1.35 Thereafter, network topology analysis was conducted with edges depicting node interactions and their degrees of significance.35\n\nCrystal X-ray structures of the target genes ESR2 [PDB: 2GIU] and ESR1 [PDB: 1QKU] were downloaded from the RCSB Protein Data Bank (PDB) (https://www.rcsb.org/) (accessed on April 01, 2024) and optimized by the elimination of all non-standard residues, co-crystallized ligands, and water molecules. Thereafter, ESR2 and ESR1 interacting metabolites and reference standards for melasma and the gene agonists tranexamic acid and tamoxifen, respectively, were developed. 3D conformers (ligands) were obtained from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/) (accessed April 01, 2024). Ligands were optimized using the Open Babel program plug-in on Python Prescription v 0.9.5 (PyRx)36 through the addition of Gasteiger charges. Binding at the gene active site was confirmed by the identification and selection of ESR2 and ESR1 active site amino acid residues. Docking studies were conducted on PyRx, from which the grid box coordinates, in correlation with the x-y-z coordinates, were ascertained using the BIOVIA Discovery Studio v21.1.0.37 Following molecular docking, the top five ligands with the highest negative docking score relative to their reference standards were visualized using Discovery Studio for their docking interactions before the simulation process. To avoid pseudo-positive binding conformations, the docking protocol was validated by measuring the root mean square deviation (RMSD) of docked ligands from the reference pocket containing native ligands (estradiol) in the experimental co-crystal Where an RMSD of 0.5 Å was obtained for both docking validations (Figure 1).38\n\nMD simulations were conducted at 150 ns using the graphical processing unit (GPU) version of the AMBER 18 package (force field with FF18SB variant) of the Center for High Performance Computing (CHPC), Cape Town, South Africa.39 Ligand atomic partial charges were harnessed through ANTECHAMBER using a general amber force field (GAFF) and restrained electrostatic potential (RESP). The systems were neutralized using hydrogen atoms and Na+ and Cl− counter ions from the Leap module. The amino acid residues of ESR2 and ESR1 were subsequently numbered and encased in an orthorhombic box of TIP3P water molecules, such that all atoms were at most 8 Å away from any box edge. The SHAKE algorithm was used to constrain hydrogen atom bonds within simulated systems, with each simulation comprising a 2 fs step-size, concurrent with the isobaric-isothermal ensemble (NPT) randomized seeding, a Langevin thermostat with a collision frequency of 1.0 ps, 1 bar, 2 ps pressure-coupling constant, and 300 K temperature. Thereafter, along with the binding free energy, the post-dynamic parameters, namely the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (RoG), and solvent-accessible surface area of each protein-ligand system were assessed.40\n\n\n3. Results\n\nA total number of 18 common metabolites were identified from the previously characterized Cassipourea species. They are comprised of different chemical classes, including fatty acids, steroids, di- and tri-terpenoids, flavonoids, and phenolic acids (Table 1).\n\nOf the 14 common metabolites of Cassipourea species whose SMILES were available in PubChem, only lyoniside had three violations of Lipinski’s Ro5 (molecular weight ≤ 500 g/mol, hydrogen bond donor and acceptor ≤ 5 and 10, respectively, bioavailability score ≤ 0.55, and lipophilicity (MLOGP) ≤ 4.5), as it had a molecular weight of 552.57 g/mol, hydrogen bond acceptor and donor of 12 and 6, respectively; other metabolites had ≤ 2 violations (Table 2). Pharmacokinetic analysis revealed that, except for sitosterol-glycosides, the metabolites were soluble in water to varying degrees. The metabolites also possess relatively high gastrointestinal absorption, are mostly non-substrate for glycoproteins, and are impermeable to the blood-brain barrier (BBB). However, azelaic acid, decahydroretinol, and emodin 6,8 dimethyl showed BBB permeability (Table 2). The metabolites demonstrated significant non-inhibition of the cytochrome P (cytochrome P450) isoenzymes (Table 2).\n\nIn total, 644 and 545 Cassipourea metabolite genes were collected from the STP and SEA databases, respectively. A total of 202 genes were common in both databases. Of the 34 melasma genes acquired from the GeneCards database and 24282 genes acquired from OMIM, only 31 genes were common to both. A further probe of the gene interactions identified four genes directly linked to Cassipourea and melasma (Figure 2).\n\nThe PPI network constructed from common genes from melasma and Cassipourea metabolites comprised 4 nodes and 12 edges, an average node degree of 2, and an enrichment p-value of 0.0107 (Figure 3). The identified estrogen receptors 1 and 2 (ESR1 and 2), prostaglandin-endoperoxide synthase 2 (PTGS2), and tyrosinase (TYR) genes interact with each other.\n\nGene ontology analysis indicated the potential effect of Cassipourea metabolites on BP, CC, and MF relative to melasma. Amongst the BP, the intracellular steroid hormone receptor signalling pathway (2.0 × 10−3) was identified as the most enriched, followed by response to vitamin D (2.9 × 10−3) and cellular response to estrogen stimulus (3.4 × 10−3). Of the CCs, only the macromolecular complex (9.8 × 10−2) was marginally enriched. Estrogen receptor activity (6.3 × 10−4) was both the most enriched MF within the GO, followed closely by enzyme binding (1.2 × 10−3) and estrogen response element binding (1.7 × 10−3) (Figure 4).\n\nKEGG pathway enrichment analysis generated five pathways, three of which were related to melasma (Figure 5). All three pathways, namely the prolactin signaling pathway (0.0238), estrogen signaling pathway (0.0238), and endocrine resistance (0.0238), shared the same FDR. To account for this, pathway strength was used to screen for the most enriched pathways. The prolactin signaling pathway was subsequently identified as the most prominent pathway (Table 2).\n\nThe resultant PCT comprised the prolactin signaling pathway, estrogen signaling pathway, and endocrine resistance (Figure 7) encompassing 13 nodes, 20 edges, and an average node degree of 3.07. From the top three pathways identified, the prolactin signalling pathway was highlighted as the most significant for its greater pathway strength (Figure 6). Network topology analysis identified seven metabolites that interact with the significant genes ESR1 and ESR2 (Figures 8 and 9).\n\nFrom the ESR2 bound Cassipourea metabolites, hexose (-5.4 kcal/mol), lupeol (-5.4 kcal/mol) and sitosterol-glycoside (-4.9 kcal/mol) had lower negative docking scores than tamoxifen (-6.2 kcal/mol) and tranexamic acid (-5.5 kcal/mol) (Table 3). Except for decahydroretinol (-6.0 kcal/mol), all ESR1-bound metabolites exhibited higher negative docking scores than both tamoxifen (-6.1 kcal/mol) and tranexamic acid (-5.9 kcal/mol) (Table 4). Observably, when bound to both ESR2 and ESR1, afzelechin exhibited the highest negative docking scores of -7.3 kcal/mol and -8.8 kcal/mol, respectively. Regarding ESR2, afzelechin formed 27 intermolecular interactions comprising two hydrogen bonds (Ile373, Arg346), 12 van der Waals interactions (Met340, Ile376, Leu362, Met294, Phe377, Leu380, Leu354, Val487, Thr299, Trp335, Leu301, Arg346), and nine other important interactions, viz. hydrophobic interactions (Glu305, Leu343, Phe356, Ala302, Leu339, Leu476, Met336, Met295, Leu298). Twenty intermolecular interactions and bonds were observed in ESR1 bound afzelechin namely, two hydrogen bonds (Phe404, Met517), 13 Van der Waals interactions (Arg394, Glu353, Thr347, Leu346, Met343, His524, Leu525, Met421, Gly521, Ser518, Ile424, Leu428, Leu387), and five other important interactions (Met388, Leu384, Leu391, Ala350, Leu349) (Tables 4 and 5).\n\nRegarding ESR2 bound systems, all Cassipourea metabolites displayed lower negative binding affinities (ranging from -18.71 kcal/mol to -40.50 kcal/mol) than tamoxifen (-47.68 kcal/mol) and higher negative binding affinities than tranexamic acid (17, 60 kcal/mol). From the top performing Cassipourea metabolites bound to ESR1, sitosterol-glycoside (-78.97 kcal/mol), decahydroretinol (-63,34 kcal/mol), lupeol (-61.23 kcal/mol), emodin 6,8 dimethyl ether (-56.45 kcal/mol), and tricin (-48.22 kcal/mol), had higher negative binding affinities than tamoxifen (-47.61 kcal/mol) and tranexamic acid (-16.68 kcal/mol), with emodin 6,8 dimethyl ether (-36.26 kcal/mol) exhibiting the lowest negative binding affinity (Table 6).\n\nWith the exception of ESR2-hexose and ESR1-tricin bound complexes at 90 ns and 120 ns, respectively, all trajectories of ESR2 and ESR1 bound and unbound systems were relatively stable and experienced minimal fluctuations (Figure 10a and 10b). Among ESR2-bound metabolites, tranexamic acid (1.44 Å) had the lowest RMSD value. Along with tranexamic acid, afzelechin (1.60 Å), emodin 6,8 dimethyl ether (1.58 Å) and sitosterol glycoside (1.59 Å) exhibited RMSD values comparable to or lower than apo-ESR2 (1.60 Å). Excluding hexose (1.98 Å), all ESR2-bound metabolites had lower RMSD values than tamoxifen (1.98 Å) (Table 7). In ESR1 bound systems, tamoxifen (1.51 Å) had the lowest RMSD value. Conversely, tranexamic acid (1.91 Å) and sitosterol-glycoside (1.91 Å) had the highest RMSD values among the ESR1-bound metabolites. Whereas tamoxifen (1.51 Å), afzelechin (1.61 Å), cassipourol (1.70 Å), decahydroretinol (1.55 Å), emodin 6,8 dimethyl ether (1.55 Å) and lupeol (1.78 Å) had similar or lower RMSD values than apo-ESR1 (1.78) (Table 7).\n\nTrajectories of ESR2 bound systems experienced a multitude of high-rising fluctuations on amino acid residues 290, 215-218, and 402-412 and again from residues to 469-482 (Figure 11a). All ESR2 bound and unbound systems had comparable RMSF values, with hexose (1.50 Å) and tranexamic acid (1.15 Å) exhibiting the highest and lowest RMSF values, respectively. Against apo-ESR2 (1.20 Å), tranexamic acid, afzelechin (1.20 Å), and emodin 6,8 dimethyl ether (1.17 Å) had lower RMSF values (Table 7). In the ESR1 bound and unbound systems, fluctuations in residues 30, 70, 230, and 247, and from residues 155-165 were prominent (Figure 11b). Besides sitosterol-glycoside (1.30 Å), cassipourol (1.28 Å), and emodin 6,8 dimethyl ether (1.21 Å), all other ESR1 bound metabolites had comparable or lower RMSF values than apo-ESR1 (1.18 Å) and tranexamic acid (1.19 Å). From the ESR1-bound metabolites, only afzelechin (1.05 Å) had a lower RMSF value than apo-ESR1, tranexamic acid, and tamoxifen (1.07 Å) (Table 7).\n\nIn the ESR2 and ESR1 bound and unbound systems, no complex fluctuations were observed (Figure 12a and 12b). The ESR2 bound systems exhibited non-significant differences in their RoG values, with decahydroretinol (17.59 Å), emodin 6,8 dimethyl ether (17.62 Å) and hexose (17.60 Å) displaying lower RoG values than tranexamic acid (17.76 Å), apo-ESR2 (17.70) and tamoxifen (17.64 Å) (Table 7). There was a marginal variance in ESR1 bound the RoG values. Excluding emodin 6,8 dimethyl ether (18.69 Å), all ESR1 bound metabolites complexes had lower RoG values than apo-ESR1 (18.67 Å), tranexamic acid (18.81 Å) and tamoxifen (18.71 Å), with tricin (18.52 Å) displaying the lowest RoG value (Table 7).\n\nExcluding ESR2 bound lupeol and ESR1 bound tricin, the trajectories of ESR2 and ESR1 bound and unbound systems experienced minor disruptions (Figure 13a and 13b). Except for sitosterol-glycoside (12397.75 Å) and lupeol (12475.06 Å), ESR2-bound metabolites exhibit lower mean SASA values than tranexamic acid (12291.71 Å), tamoxifen (12227.35 Å) and apo-ESR2 (12411.51 Å), with tricin (11892.74 Å) exerting the most impact on the SASA (Table 7). In ESR1 bound and unbound systems, tranexamic acid (13706.67 Å) had the highest SASA value. ESR1 bound cassipourol (13672.21 Å), Emodin 6,8 dimethyl ether (13615.75 Å) and lupeol (13602.97 Å) exhibited higher SASA values than tamoxifen (13558.03 Å) and apo-ESR1 (13584.25 Å), with afzelechin (12995.41 Å) exhibiting the lowest SASA value (Table 7).\n\nThe 2D interaction plots of ESR2 bound systems displayed the formation of hydrogen bonds (carbon-hydrogen, pi-hydrogen donor, and conventional), hydrophobic interactions (pi-pi-T-shaped, alkyl, pi-alkyl, pi-sulfur, pi-cation, amide-pi-stacked, attractive charge, salt bridge, and unfavorable donor-donor bonds), and van der Waals interactions (Figure 14). From 0 ns to 150 ns, afzelechin is unable to maintain hydrogen bond formation (4 → 1) and forgoes its unfavorable donor-donor bond to form a π-sulfur bond, thus maintaining six important interactions and bonds (Figure 14a). Decahydroretinol retains six hydrophobic interactions at 0 ns and 150 ns but is unable to maintain its hydrogen bonds (2 → 1) I (Figure 14b). Emodin 6,8 dimethyl ether formed nine hydrophobic interactions and three hydrogen bonds at 0 ns, which were reduced to seven hydrophobic interactions and two hydrogen bonds at 150 ns (Figure 14c. However, at 0 and 150 ns, hexose formed four and seven hydrogen bonds, respectively, and experienced a decrease in the total intramolecular interactions from 15 to 13 (Figure 14d). At 150 ns, lupeol was unable to maintain hydrogen bond formation on Arg81 and retained only four hydrophobic interactions (Figure 14e). Sitosterol-glycoside retained four hydrogen bonds at 0 ns and 150 ns and formed a hydrophobic alkyl interaction on Met292 at 150 ns (Figure 14f). Regarding tricin, at 0 ns and 150, the number of hydrogen bonds decreased from five to four, and the number of hydrophobic interactions increased from three to four (Figure 14g). Based on its interactions at 0 ns, tranexamic acid was unable to retain its hydrogen bond (one), hydrophobic interactions, and intramolecular interactions (12) at 150 ns (Figure 14h). Although tamoxifen was able to maintain its hydrophobic interactions (seven) at 0 and 150 ns, it did not retain its hydrogen bond formation (one) or intramolecular interactions (22) (Figure 14i).\n\nA probe into the binding interactions of ESR1 and its metabolites revealed the presence of hydrogen bonds, van der Waals interactions, and hydrophobic interactions such as pi-sulfur, pi-alkyl, alkyl, pi-pi-T-shaped, amide-pi-stacked, pi-sigma, and unfavorable donor-donor interactions (Figure 15). At 0 and 150 ns, afzelechin retained its five hydrophobic interactions and formed four hydrogen bonds at 150 ns (Figure 15a). From 0 to 150 ns, cassipourol forms nine hydrophobic interactions and two hydrogen bonds (Figure 15b). Decahydroretinol maintains one hydrogen bond and, in total, forms 11 hydrophobic interactions from 0 to 150 ns (Figure 15c). Against emodin 6,8 dimethyl ether’s intramolecular interactions at 0 ns, hydrogen bond formation increased to two, and hydrophobic and total intramolecular interactions decreased to nine and 18, respectively (Figue 15d). Lupeol exhibited hydrogen bond formation on Phe101 and an increase in hydrophobic (10) and intramolecular interactions (23) (Figure 15e). Sitosterol-glycoside forms three hydrogen bonds and replaces the three unfavorable bumps with eight hydrophobic alkyl interactions (Figure 16f). At 0ns and 150 ns, tricin forms two and five hydrogen bonds, respectively, and forgoes the unfavorable acceptor bond at 0ns for eight hydrophobic interactions (Figure 15g). In tranexamic acid, from 0 ns to 150 ns, hydrogen bond formation increased to three, intramolecular interactions were altered to 18, and hydrophobic interactions decreased to two (Figure 15h). Similarly, in tamoxifen, hydrogen bonds and intramolecular interactions are increased to two and 22, respectively, and hydrophobic interactions are reduced to six (Figure 15i).\n\n\n4. Discussion\n\nSeveral studies have established the benefits of natural products, including plants, for various biological purposes.41 Metabolites identified in the Cassipourea species are reportedly implicated in skin pigmentation, treatment of skin diseases, and inhibition of tyrosinase activity.20,24 Specifically, azelaic acid, a dicarboxylic acid found in many grains, has been reported to possess anti-tyrosinase and anti-inflammatory effects,42 whereas lupeol and its derivatives are implicated in wound healing.43 These studies corroborate the therapeutic potential and identify putative leads of Cassipourea metabolites in melasma.\n\nInterestingly, Cassipourea metabolites demonstrated remarkable drug-likeness and pharmacokinetic properties, indicating their use not only as potential topical agents but also as oral drug candidates for melasma treatment. This is evident by the finding that most metabolites are in conformity with Lipinski’s Ro5 for oral drug candidates and show appreciable bioavailability for therapeutic applications. In addition, the metabolites were relatively non-inhibitors of CYP450 enzymes; hence, they can be easily biotransformed into more polar and excretable by-products in biological systems. The GIA and Pgp-S profiles also potentiated Cassipourea for both applications. For example, sitosterol-glycoside and lupeol are hydrophobic compounds, and their low GIA and poor solubilities are suggestive of their biological effect being more applicable topically with potentially longer-lasting and better effects on the skin due to their hydrophobicity. To gain further insight into the mechanism of action of Cassipourea metabolites in melasma treatment, NP and MD simulations were conducted.\n\nAlthough only four genes were common between Cassipourea metabolites and melasma, they have been reported to exert significant effects on skin pigmentation and melasma. Factors that reportedly affect the pathogenesis of melasma include genetics and hormonal activity.44 Estrogen is a female sex hormone that influences skin pigmentation by stimulating melanin synthesis in melanocytes, improving skin tonicity, thickness, healing, elasticity, and preventing age-related diseases when produced in adequate amounts.45 Estrogen levels differ with stages in women; for example, estrogen levels gradually rise from the pre-menopausal to childbearing stages, followed by a decline during post-menopause. This could be attributed to the reduction in melanin synthesis with increasing age.45\n\nEstrogen exerts its effects through signalling pathways and genes that are important in skin physiology and pathology. Dysregulation of estrogen gene activity in the skin might result in abnormal skin pigmentation, including melasma. Furthermore, overexpression of ESR2 has been implicated in melasma.46 Melasma is more prominent during pregnancy, hormone replacement therapy, and oral contraceptive use.47 The observation that estrogen genes, receptors, and signalling pathways were some of the most enriched genes in the PPI, the most significant molecular functions in the GO analysis, and the second most significant signalling pathway KEGG, respectively, in this study lend credence to the vital role of Cassipourea metabolites in melasma treatment.\n\nThe PTGS2 gene (cyclooxygenase 2) stimulates the synthesis of prostanoids, such as prostaglandins, thromboxanes, and protacyclins, involved in inflammation caused by the 20-C atom arachidonic acid.48 Therefore, through the modulation of PTGS2, Cassipourea metabolites may regulate melasma-induced inflammatory responses. Furthermore, sitosterol has been reported to be an anti-inflammatory agent.49 The involvement of tyrosinase (TYR) in the PPI network corroborates the findings of Mpofana et al. 2023,20 who stated that Cassipourea metabolites possess an anti-tyrosinase effect. TYR regulates melanin synthesis; hence, its inhibition aids in replenishing normal skin pigmentation and decreasing the risk of melasma.\n\nThe finding that the intracellular steroid hormone receptor signalling pathway was the most enriched biological process in the GO analysis denotes the potential of Cassipourea metabolites in the treatment of melasma. Other biological processes, such as cellular response to estrogen and estradiol stimulus, estrogen receptor signalling pathway, and regulation of inflammatory response, have also been implicated in skin pigmentation. However, steroid hormones, such as estrogen, estradiol, and progesterone, have been implicated in the control of skin pigmentation via certain receptors.50 These hormones, as well as the overexpression of tyrosinase and melanocyte-stimulating hormone, are attributed to the excessive pigmentation observed during pregnancy.51 The interaction of these steroid hormones and signalling pathways is suggestive of the possible role of Cassipourea in preventing pregnancy-induced melasma. Interestingly, the signalling pathways and genes identified in this study are in line with the study by Yin et al.,25 who studied the mechanism of action of Croci stigma on melasma.\n\nThe hyperstimulation of melanocytes by UV irradiation also induces high melanin secretion and ROS generation, resulting in cellular damage.44 Vitamin D plays an important role in skin functions, including skin homeostasis and anti-inflammatory, immune, and cell proliferation responses that are essential for wound healing and restoration of skin pigmentation anomalies.52 The observation that response to vitamin D was one of the most enriched biological processes denotes the ability of Cassipourea metabolites to stimulate vitamin D production, which is necessary to prevent UV-induced melasma.\n\nHowever, the macromolecular complex was the only enriched cellular component. This complex is vital to cellular processes. It is composed of assemblies of proteins and nucleic acids involved in transcriptional and translational processes that convert DNA to RNA and protein, respectively. In signaling pathways, these assemblies are transient,53 which might imply that melasma temporarily affects signaling pathways and that skin anomalies could be restored to normalcy upon appropriate treatment.\n\nProlactin, a hormone secreted during lactation and reproduction, is involved in metabolism, immunoregulation, protection, growth, and development. The binding of prolactin to the prolactin receptor initiates the prolactin signaling pathway.54 The observation that the prolactin signalling pathway was the most enriched in the KEGG analysis signifies that the functions of prolactin, its predominance in females who are largely affected by melasma, and the activation of its signalling pathway during the reproductive process, the regulation of this pathway could also serve as a target for the action of Cassipourea metabolites. Furthermore, the most significant genes (ESR2 and ESR1) in this pathway were analyzed for their binding affinity, stability, and interaction with top-ranked metabolites.\n\nMolecular docking identifies the top therapeutic metabolites by assessing their binding affinity for the active site of selected receptors to further augment the understanding of their bioactive mechanisms of action.55 Higher negative docking scores are associated with better docking poses and fitness.56 Except for ESR2-bound hexose, lupeol, sitosterol-glycoside, and ESR1-bound decahydroretinol, the higher negative docking scores of receptor-bound Cassipourea metabolites, relative to tamoxifen and tranexamic acid, are suggestive of their better biological activity.57 Afzelechin acts as a dual modulator of both ESR2 and ESR1, with the highest negative docking scores within each receptor-bound system, further highlighting its potential therapeutic application. However, molecular docking merely assesses the crystallographic binding orientation of ligands, while molecular dynamic (MD) simulations help to elucidate binding stability.58\n\nTo better understand the biomolecular affinity and efficacy of Cassipourea metabolites as therapeutic candidates, their thermodynamic binding free energies were analyzed over 150 ns,59 with higher negative values indicative of greater binding affinity. The higher negative binding free energy of tamoxifen than that of ESR2-bound metabolites suggests that tamoxifen offers marginal superiority as an ESR2 modulator. The lower negative binding free energy of tranexamic acid relative to that of ESR2-bound metabolites indicates that Cassipourea metabolites are more thermodynamically stable. Comparatively, the higher negative binding free energies of ESR1 bound cassipourol, decahydroretinol, lupeol, tricin, and sitosterol-glycoside complexes with tamoxifen and tranexamic acid were presumed to be stable and had better modulatory effects on ESR1. Moreover, MD simulations identified sitosterol-glycoside as a dual modulator of ESR2 and ESR1 because of its high negative binding free energy and superior thermodynamic stability among all other Cassipourea metabolites, further augmenting its biological activity in melasma-based therapeutics.\n\nThereafter, the post-dynamic parameters RMSD, RMSF, RoG, and SASA of the ESR2 and ESR1 bound systems were assessed at 150 ns for better insight into their thermodynamic stability.60 RMSD measures the stability of protein-ligand systems by quantifying the change between their initial and final structural conformation, with lower deviations (values) denoting greater stability.61 According to Umar et al.,62 an RMSD value of ≤ 3 Å is an acceptable measurement of protein-ligand stability, validating the stability of ESR2 and ESR1 bound and unbound systems. The lower RMSD of the ESR2-bound tranexamic acid and ESR1-bound tamoxifen complexes is presumed to be due to their better stability as modulators of their respective genes. Conversely, the higher RMSD of ESR2-bound tamoxifen and ESR1-bound tranexamic acid systems compared to Cassipourea metabolites suggests their potential stability with the ESR2 and ESR1 genes. Comparatively, the lower RMSD of ESR2-bound emodin ethyl ether and sitosterol-glycoside and ESR1-bound afzelechin, cassipourol, decahydroretinol, emodin 6,8 dimethyl ether, and lupeol against their apo-genes indicated that these metabolites formed stable complexes with their relative genes.\n\nRMSF analysis of ESR2 and ESR1 bound and unbound systems measures the flexibility of protein-ligand interactions. Higher RMSF values and fluctuations denote greater flexibility but less stability, whereas lower RMSF values and fluctuations indicate greater stability.63 Generally, an RMSF value <2 Å is an optimal measure of ligand flexibility.64 Thus, all metabolites bound to ESR2 and ESR1 exhibited suitable flexibility, with ESR2-bound emodin 6,8 dimethyl ether and ESR1-bound afzelechin, decahydroretinol, and lupeol exerting stabilizing effects on their relative apo-genes. However, among Cassipourea metabolites, tranexamic acid may potentiate greater stability as an ESR2 modulator, and tamoxifen may exhibit comparable flexibility as an alternate ESR1 modulator.\n\nThe RoG measures the time-dependent compactness of protein-ligand systems, with lower values indicating greater overall compactness and stability.65 The similar RoG values of the ESR2 and ESR1 bound systems relative to their apo-genes are suggestive of the marginal impact exerted by Cassipourea metabolites on ESR2 and ESR1 protein folding. The lower RoG values of ESR2-bound decahydroretinol, emodin 6.8 dimethyl ether, and hexose complexes and ESR1-bound afzelechin, cassipourol, decahydroretinol, sitosterol-glycoside, lupeol, and tricin complexes relative to tranexamic acid, tamoxifen, and their apo-genes are indicative of their greater compactness, stability, and suitability as ESR2 and ESR1 modulators.\n\nThe SASA plot was used to measure the rate of interaction between complexes and their surrounding hydrophobic environment, with higher values denoting greater environmental exposure and lower values depicting more stable systems.66 The lower SASA values of ESR2-bound metabolites (excluding lupeol) and ESR1-bound metabolites (excluding emodin 6,8 dimethyl ether, cassipourol, and lupeol) relative to their apo-genes suggest Cassipourea metabolites induce protein-ligand stability and compactness through protein folding. The minor fluctuations experienced by ESR2-bound lupeol at 125 ns and ESR1-bound tricin and cassipourol at 85 ns and 105 ns, respectively, suggest less interaction during that period. The lower SASA values of ESR2 bound afzelechin, hexose, emodin 6,8 dimethyl ether, decahydroretinol, and tricin complexes and ESR1 bound afzelechin, decahydroretinol, sitosterol-glycoside, and tricin complexes relative to tamoxifen and tranexamic acid are presumptive of their weaker interactions with the surrounding hydrophobic environment, resulting in better stability and modulation of ESR2 and ESR1.\n\nThe presence of hydrogen bonds significantly induces protein-ligand stability, binding specificity, and several pharmacokinetic properties such as metabolism and adsorption.67 The 2D interaction plots of ESR2 and ESR1 bound systems also formed van der Waals and hydrophobic interactions, both of which augment their stability and affinity. In both ESR2 and ESR1 systems, sitosterol-glycoside could retain and steadily increase its hydrogen bond formation, corroborating its highest negative binding free energy among Cassipourea metabolites in both systems. The higher negative binding free energy of ESR2-bound tamoxifen can be attributed to the formation of multiple hydrophobic interactions throughout the 150 ns simulation.\n\n\n5. Conclusions\n\nThe results of this study provide pharmacological support for the development of an alternative treatment for the management of hypermelanosis disorders such as melasma. The constituents of Cassipourea have potential commercial value. The finding that several sex hormones implicated in melasma, transcription processes, and vitamin D are highly involved in this study is a strong indication of the multi-target pathways by which Cassipourea metabolites potentially exert effects on melasma. The potential regulation of estrogen synthesis by these metabolites, depicted by their binding interactions, stability, and compactness, is suggestive of melanogenesis control for normal skin pigmentation and the possible restoration of melasma skin. Further studies are recommended to validate and assess the safety of these metabolites.\n\nThe study was conducted following the approval of the University of KwaZulu-Natal Biomedical Research Ethics Committee (UKZN BREC) (protocol reference number: BREC/00002721/2021).\n\nConceptualization: NM; methodology: NM; CP and SS; software: SS.; formal analysis: SS, CP, and HYL; investigation: NM, CP, and SS.; resources: SS; writing: original draft preparation: NM, CP, and HYL; writing: review and editing, NM, CP, HYL, SS, and MUM.; visualization, SS; supervision: NCD, NG, and AH; funding acquisition: NM and NG. All authors have read, agreed to, and approved the final version of the manuscript.",
"appendix": "Data availability statement\n\nFIGSHARE: Compounds elucidated from the three selected Cassipourea species as well as phytochemical comparison, https://doi.org/10.6084/m9.figshare.26418361.v1. 68\n\nThe project contains the following underlying data:\n\n• Compounds elucidated from the three selected Cassipourea species\n\n• Phytochemical comparison of the compounds\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nAll the methods used in the study were adequately detailed in the “Methodology Section” of the manuscript and the followed the standard guidelines on reporting computational biology studies.\n\n\nReferences\n\nGilaberte Y, et al.: Anatomy and Function of the Skin. Nanoscience in dermatology. Elsevier; 2016; pp. 1–14. Publisher Full Text\n\nSingh M, Sharma V: Spectrophotometric determination of Sun Protection Factor and antioxidant potential of an herbal mixture. Br. Biotechnol. J. 2016; 10: 1–8. 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Plants. 2023; 12(12): 2281. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhu W, Gao J: The use of botanical extracts as topical skin-lightening agents for the improvement of skin pigmentation disorders. J. Investig. Dermatol. Symp. Proc. 2008. Elsevier.\n\nFahmy NM, et al.: Chemical exploration of different extracts from Phytolacca americana leaves and their potential utilization for global health problems: ın silico and network pharmacology validation. J. Biomol. Struct. Dyn. 2024; 1–21. PubMed Abstract | Publisher Full Text\n\nMpofana N, et al.: Analysis of Three Species of Cassipourea Traditionally Used for Hypermelanosis in Selected Provinces in South Africa. Int. J. Mol. Sci. 2023; 25(1): 237. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMwinga J, et al.: Botanicals used for cosmetic purposes by Xhosa women in the Eastern Cape, South Africa. S. Afr. J. Bot. 2019; 126: 4–10. Publisher Full Text\n\nThibane V, et al.: The cosmetic potential of plants from the Eastern Cape Province traditionally used for skincare and beauty. S. Afr. J. Bot. 2019; 122: 475–483. Publisher Full Text\n\nThibane V, et al.: Modulation of the enzyme activity of secretory phospholipase A2, lipoxygenase and cyclooxygenase involved in inflammation and disease by extracts from some medicinal plants used for skincare and beauty. S. Afr. J. Bot. 2019; 120: 198–203. Publisher Full Text\n\nLangat MK, et al.: The effect of isolates from Cassipourea flanaganii (Schinz) alston, a plant used as a skin lightning agent, on melanin production and tyrosinase inhibition. J. Ethnopharmacol. 2021; 264: 113272. PubMed Abstract | Publisher Full Text\n\nYin W, et al.: The mechanism of Croci stigma in the treatment of melasma based on network pharmacology and molecular docking. J. Cosmet. Dermatol. 2023; 22(7): 2105–2114. PubMed Abstract | Publisher Full Text\n\nLipinski CA, et al.: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 1997; 23(1-3): 3–25. Publisher Full Text\n\nDaina A, Michielin O, Zoete V: SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017; 7(1): 42717. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShannon P, et al.: A software environment for integrated models of biomolecular interaction networks.2003; 13: 2498–2504. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFan Z, et al.: Network Pharmacology and experimental validation to reveal the pharmacological mechanisms of chongcaoyishen decoction against chronic kidney disease. Front. Mol. Biosci. 2022; 9: 847812. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSzklarczyk D, et al.: The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021; 49(D1): D605–D612. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZeng Z, et al.: Network pharmacology and molecular docking-based prediction of the mechanism of Qianghuo Shengshi decoction against rheumatoid arthritis. Biomed. Res. Int. 2021; 2021: 1–12. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuang DW, et al.: The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol. 2007; 8: R183–R116. Publisher Full Text\n\nWu T, et al.: clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. The innovation. 2021; 2(3): 100141. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYu G, et al.: DOSE: an R/Bioconductor package for disease ontology semantic and enrichment analysis. Bioinformatics. 2014; 31(4): 608–609. PubMed Abstract | Publisher Full Text\n\nSakle NS, More SA, Mokale SN: A network pharmacology-based approach to explore potential targets of Caesalpinia pulcherima: An updated prototype in drug discovery. Sci. Rep. 2020; 10(1): 17217. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDallakyan S, Olson AJ: Small-molecule library screening by docking with PyRx. Methods Mol. Biol. 2015; 1263: 243–250. PubMed Abstract | Publisher Full Text\n\nBiovia DS: Discovery Studio, version 21.1. 0. San Diego: Dassault Systèmes; 2021; 627.\n\nLukman H, et al.: Modulation of dipeptidyl peptidase by Rooibos tea metabolites towards type 2 diabetes care: Evidence from molecular dynamics simulation and density functional theory. Scientific African. 2024; 24: e02173. Publisher Full Text\n\nNair PC, Miners JO: Molecular dynamics simulations: from structure function relationships to drug discovery. In Silico Pharmacol. 2014; 2: 1–4. Publisher Full Text\n\nAribisala JO, S’thebe NW, Sabiu S: In silico exploration of phenolics as modulators of penicillin binding protein (PBP) 2× of Streptococcus pneumoniae. Sci. Rep. 2024; 14(1): 8788. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIbrahim SO, et al.: An Insight into the Physicochemical, Drug-likeness, Pharmacokinetics and Toxicity Profile of Kigelia africana (Lam) Bioactive Compounds. Al-Bahir Journal for Engineering and Pure Sciences. 2024; 4(1): 4. Publisher Full Text\n\nAlbzea W, et al.: Azelaic Acid Versus Hydroquinone for Managing Patients With Melasma: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cureus. 2023; 15(7). Publisher Full Text\n\nMalinowska MA, et al.: The effect of the new lupeol derivatives on human skin cells as potential agents in the treatment of wound healing. Biomolecules. 2021; 11(6): 774. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEspósito ACC, et al.: Update on Melasma—Part I: Pathogenesis. Dermatol. Ther. 2022; 12(9): 1967–1988. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCaruntu C, et al.: The role of estrogens and estrogen receptors in melanoma development and progression. Acta Endocrinologica (Bucharest). 2016; 12(2): 234–241. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu W, Chen Q, Xia Y: New mechanistic insights of melasma. Clin. Cosmet. Investig. Dermatol. 2023; 16: 429–442. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHandel A, et al.: Risk factors for facial melasma in women: a case–control study. Br. J. Dermatol. 2014; 171(3): 588–594. PubMed Abstract | Publisher Full Text\n\nSmith WL, Garavito RM, DeWitt DL: Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and− 2. J. Biol. Chem. 1996; 271(52): 33157–33160. Publisher Full Text\n\nPaniagua-Pérez R, et al.: Evaluation of the anti-inflammatory capacity of beta-sitosterol in rodent assays. Afr. J. Tradit. Complement. Altern. Med. 2017; 14(1): 123–130.\n\nNatale CA, et al.: Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors. elife. 2016; 5: e15104. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGoandal NF, Rungby J, Karmisholt KE: The role of sex hormones in the pathogenesis of melasma. Ugeskr. Laeger. 2022; 184(6): V10210769–V10210769.\n\nChen Q, Liu L, Zhang Y: Vitamin D and wound healing: Assessing skin barrier function and implications for chloasma treatment. Int. Wound J. 2024; 21(1): e14541. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAppasamy SD, et al.: Annotating Macromolecular Complexes in the Protein Data Bank: Improving the FAIRness of Structure Data. Sci Data. 2023; 10(1): 853. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRadhakrishnan A, et al.: A pathway map of prolactin signaling. Springer; 2012.\n\nAgu P, et al.: Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Sci. Rep. 2023; 13(1): 13398. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAkoonjee A, et al.: Waste to Medicine: Evidence from Computational Studies on the Modulatory Role of Corn Silk on the Therapeutic Targets Implicated in Type 2 Diabetes Mellitus. Biology. 2023; 12(12): 1509. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMacip G, et al.: Haste makes waste: a critical review of docking-based virtual screening in drug repurposing for SARS-CoV-2 main protease (M-pro) inhibition. Med. Res. Rev. 2022; 42(2): 744–769. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRamírez D, Caballero J: Is it reliable to take the molecular docking top scoring position as the best solution without considering available structural data? Molecules. 2018; 23(5): 1038. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHata H, et al.: Binding free energy of protein/ligand complexes calculated using dissociation Parallel Cascade Selection Molecular Dynamics and Markov state model. Biophys. Physicobiol. 2021; 18: 305–316. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRampadarath A, et al.: Molecular bioprospection of Helianthus annuus L.(sunflower) cypsela for antidiabetic therapeutics through network pharmacology, density functional theory and molecular dynamics simulation. S. Afr. J. Bot. 2023; 162: 72–95. Publisher Full Text\n\nAier I, Varadwaj PK, Raj U: Structural insights into conformational stability of both wild-type and mutant EZH2 receptor. Sci. Rep. 2016; 6(1): 34984. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRamírez D, Caballero J: Is it reliable to use common molecular docking methods for comparing the binding affinities of enantiomer pairs for their protein target? Int. J. Mol. Sci. 2016; 17(4): 525. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSingh K, et al.: Computational insights and in vitro validation of antibacterial potential of shikimate pathway-derived phenolic acids as NorA efflux pump inhibitors. Molecules. 2022; 27(8): 2601. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUmar AK, et al.: Structure-based computational screening of 470 natural quercetin derivatives for identification of SARS-CoV-2 Mpro inhibitor. PeerJ. 2023; 11: e14915. Publisher Full Text\n\nAribisala JO, Sabiu S: Cheminformatics identification of phenolics as modulators of penicillin-binding protein 2a of Staphylococcus aureus: A structure–activity-relationship-based study. Pharmaceutics. 2022; 14(9): 1818.\n\nSulyman AO, et al.: Bioprospection of Selected Plant Secondary Metabolites as Modulators of the Proteolytic Activity of Plasmodium falciparum Plasmepsin V. Biomed. Res. Int. 2023; 2023. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWilliams M, Ladbury J: Hydrogen bonds in protein-ligand complexes. Protein-ligand interactions: from molecular recognition to drug design.2003; 137–161.\n\nMpofana N: Compounds elucidated from the three selected Cassipourea species as well as phytochemical comparison. figshare. Figure. 2024. Publisher Full Text"
}
|
[
{
"id": "316598",
"date": "10 Sep 2024",
"name": "Jared Jagdeo",
"expertise": [
"Reviewer Expertise melasma",
"phototherapy",
"keloids",
"basic science research",
"AN",
"cosmetics",
"skin of color"
],
"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: The background, methods, results, and conclusion are briefly described. The authors clearly state the study objectives and a concise rationale for the study. The experimental results and conclusions are well represented, giving readers a good sense of the research and the key takeaways. In the methods section of the abstract, the information provided is general and does not provide sufficient detail to readers. Additional information regarding the three specific metabolites, how the molecular docking and simulation were performed, what softwares were utilized and structures used, etc. would help provide substance and clarity. Introduction: The authors present a thorough background on the known pathogenesis of melasma, the role of melanin, and existing treatment options. An epidemiological background is also provided but could benefit from including the disproportionate impact and disease burden on populations with skin of color, as well as their more limited treatment options. Additionally, since melasma is known as the 'mask of pregnancy,' the association with pregnancy should be included. This would offer a more robust introduction and more effectively communicate the impact of this research. The sentences addressing the value and history of secondary metabolites could be strengthened by providing concrete example(s) of previously discovered secondary metabolites that have played 'protection and treatment roles against various diseases.' We also recommend the authors provide more comprehensive details on the current evidence for the three Cassipourea species. This would help strengthen the justification for their analyses. Lastly, the authors should grammatically revise the first sentence of the sixth paragraph: 'Studies have explored natural products that inhibit UV-induced ROS, suppress enzymes, and reduce melanin formation as potential alternatives to current treatments have been conducted.' Methods: The methods effectively support the goals of the experiment. The organization and division into subsections make the protocol easy to follow. The purpose of each analysis is clear and well justified. However, additional context would strengthen the robustness of the methodology. Specifically, in section 2.1, we recommend that the authors list the three Cassipourea species. In section 2.2, we suggest briefly describing Lipinski’s Rule of Five (as referenced later in Section 3.2) and its purpose within the context of this study. Results: The results are presented clearly with supporting tables and figures. The figures are well displayed and effectively convey the data in a concise and logical manner. The information supports the goals of the experiment and the conclusions drawn. However, in all figure legends, the authors should not only describe the methods used but also briefly summarize the main findings from the figures and their corresponding experiments. Additionally, the authors should redefine all abbreviations used within the figures for clarity. Lastly, in Figure 2, the GeneCards/OMIM Venn diagram requires clarification and correction, as the number of genes identified as common to both GeneCards and OMIM exceeds the number of metabolite genes identified by GeneCards alone. Discussion: The discussion highlights the novelty and value of this research, efficiently yet comprehensively discussing each of the study's results. The authors effectively convey how each analysis and result builds upon the previous one, providing sufficient contextual information for readers to fully appreciate the implications of the findings. While Figures 14 and 15 are helpful visual representations, we recommend adjusting the sizing and formatting of the keys for better readability. Additionally, we suggest examining any limitations of the study, including those related to the technologies the authors relied on to perform the analyses. Conclusion: The conclusion briefly and effectively summarizes the study's purpose and the key takeaways from the discussion. We recommend expanding upon potential future directions, including future research and clinical applications. General comments: The paper is well-written overall. The information is presented clearly and completely. The writing style is scientific and professional. The goals of the study, the methods, and results/conclusions are clear, justified, and strong. Our specific comments are as stated above. Decision: Minor revisions\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12482",
"date": "25 Sep 2024",
"name": "Nomakhosi Mpofana",
"role": "Author Response",
"response": "Reviewer comment: Are sufficient details of methods and analysis provided to allow replication by others?: Partly Response: Thank you for your feedback. To address your concern about the sufficiency of details provided for replication, we would like to ask for your help in identifying specific methods or aspects of our analysis that you found unclear, in order for us to amend the sections as required. Are all the source data underlying the results available to ensure full reproducibility?: Partly Response: Thank you for your comment. To better address this comment, please advise which specific aspects of the results you found unclear or inadequately supported by the source data. Identifying these areas will allow us to provide the necessary information and increase the transparency of our results."
}
]
}
] | 1
|
https://f1000research.com/articles/13-952
|
https://f1000research.com/articles/13-950/v1
|
22 Aug 24
|
{
"type": "Review",
"title": "The epidemiologic case for urban health: conceptualizing and measuring the magnitude of challenges and potential benefits",
"authors": [
"Michael D. Garber",
"Tarik Benmarhnia",
"Audrey de Nazelle",
"Mark Nieuwenhuijsen",
"David Rojas-Rueda",
"Tarik Benmarhnia",
"Audrey de Nazelle",
"Mark Nieuwenhuijsen",
"David Rojas-Rueda"
],
"abstract": "We discuss how epidemiology has been and can continue to be used to advance understanding of the links between urban areas and health informed by an existing urban-health conceptual framework. This framework considers urban areas as contexts for health, determinants of health and modifiers of health pathways, and part of a complex system that affects health. We highlight opportunities for descriptive epidemiology to inform the context of urban health, for example, by characterizing the social and physical environments that give rise to health and the actions that change those conditions. We then describe inferential tools for evaluating the impact of group-level actions (e.g., interventions, policies) on urban health, providing some examples, and describing assumptions and challenges. Finally, we discuss opportunities and challenges of applying systems thinking and methods to advance urban health. While different conceptual frames lead to different insights, each perspective demonstrates that urban health is a major and growing challenge. The effectiveness of urban health knowledge, action, and policy as the world continues to urbanize can be informed by applying and expanding upon research and surveillance methods described here.",
"keywords": [
"Urban health",
"Epidemiology",
"Global health",
"Policy evaluation",
"Public health surveillance"
],
"content": "Key messages\n\n\n\n• The health of urban residents is a major component of global health and will become more important with continuing urbanization.\n\n• Urban areas share common health-relevant environmental and social features, but the health of urban residents and the impact of urban living on health vary between and within cities.\n\n• As a previously published conceptual framework articulates, the links between urban environments and population health can be conceptualized in various ways, including as the setting in which population health occurs, as a cause of population health, and as part of a complex system that shapes population health. Each conceptualization raises distinct challenges and opportunities regarding measurement of scale and impacts.\n\n• Classical tools of descriptive epidemiology remain important for the study of urban health, and more complete health-outcome data on health is needed at the city- and within-city scales.\n\n• Where direct observation is not feasible, health-impact modeling and small-area estimation show promise for advancing the description of urban health outcomes at high spatial resolution.\n\n• There is a need for higher resolution and more systematic measurement of the physical, social, and policy environments that affect urban health, a task that can be considered within the purview of descriptive epidemiology.\n\n• Research on the impact of actions and interventions on urban health and health equity interventions is limited. Evaluating these actions using longitudinal methods for group-level data should continue.\n\n\n1. Introduction\n\nAs the proportion of humanity living in cities continues to rise, the health of people living in urban areas will represent an increasingly important component of global health.1 In 2018, the share of the world’s population residing in urban areas was 55% and is expected to increase to 60% by 2030.1 Urbanization (the process of an area becoming more urban) is accelerating in particular in low- and middle-income countries in Asia and Africa.1 A clear implication of global urbanization trends is that improving public health globally will require a major focus on health in urban areas.2 However, the scale of current and future urban health challenges and opportunities is not well characterized and depends on assumptions about the nature of the relationships between cities and health and the scope of urban health action.\n\nUrban areas present both challenges and opportunities for public health.3–5 Compared with rural areas, urban areas can promote health through higher standards of living and better access to resources and services, including healthcare services.6–8 Nevertheless, characteristics common to many urban environments can also harm health, including air pollution;9 noise pollution; heat exacerbated by urban heat islands;10 inadequate green space; high availability of nutrient-poor, calorie-dense food; and unsafe transportation systems resulting in road traffic injuries and discouraging physical activity.6,11 Urban areas are also vulnerable to some infectious diseases. Some, such as COVID-19,12 may spread rapidly in areas with high population density and connectivity.11 Others, such as malaria, have historically been more common in rural areas,13 but climate change and landscape modifications including deforestation are changing spatial patterns of vector-borne diseases, increasing their occurrence in urban areas.14\n\nWhile urban areas can share common health-relevant environmental and social features, cities are distinct, and the health of urban residents—and the impact of urban living on health—varies both between and within cities.15,16 Variable exposure to environmental conditions (both social and physical) gives rise to health inequities in urban populations by characteristics such as income and wealth, residential neighborhood, race and ethnicity, age, disability, gender identity, sexual orientation, or migration status.16 Ultimately, variation in health between and within cities reveals an opportunity: urban areas can be designed and managed to promote health and health equity. Furthermore, in the context of global climate change, strategies to improve health in cities can have co-benefits for climate-change mitigation and adaptation.17–19 Given this opportunity, there is a need for a clearer understanding of how urban environments and the forces that change them affect public health and of the scale of the health challenges and opportunities inherent in the urban context.\n\nMany disciplines will contribute to this needed understanding, and epidemiologists, those who study the distribution and determinants of health in populations, are well-equipped to contribute in several ways. Some tools from epidemiology, in particular descriptive epidemiology, have an established history of informing urban health. Other more contemporary topics in epidemiology, such as methods for causal inference, have yet to realize their potential in helping to answer urban-health questions. At the same time, the discipline may be well-suited to advance urban-health knowledge in ways traditionally not under its purview, such as the surveillance of the urban physical and policy environment. In this article, we discuss how epidemiology has been and can continue to be used to advance understanding of the links between urban areas and health informed by an existing urban-health conceptual framework. We then propose actions needed to continue to advance this understanding.\n\n\n2. Conceptualizing and measuring urban health\n\nUrban-health scholars have proposed various frameworks to represent and explain the links between urban environments and population health.6,20–25 In the framework by Diez Roux presented in Chapter 3 of the Urban Public Health text, the links are conceptualized in four inter-related ways.24 First, urban areas are contexts for health. That is, they are settings in which population health occurs. Second, urban areas are causes or determinants of health. These place-based causes occur at various levels, for example, the neighborhood (e.g., features of its built environment) or the city (e.g., housing policy). Third, and related to the second, urban areas can modify or reinforce individual-level health pathways. For example, genetic susceptibility to obesity can be modified by the neighborhood food environment.26 Fourth—and encompassing each of the above—urban areas are part of complex systems that shape population health.6,21,27 Measuring the magnitude of urban-health challenges through each of these lenses has value for researchers, policymakers, and advocates.\n\n2.2.1 Describing health-related states and behaviors in urban populations\n\nThe most conceptually straightforward link between urban areas and health is the occurrence of diseases, health-related states, and behaviors among individuals living in urban areas. Measuring these outcomes in urban areas is important for planning and resource allocation, monitoring progress on health targets over time, comparing the distribution of health between groups, generating hypotheses, and identifying opportunities for intervention. This task has traditionally been undertaken by public health surveillance systems (such as vital statistics registries and large-scale cross-sectional surveys), cohort studies, and other tools of descriptive epidemiology. For example, national registries have been used to compare cancer incidence between urban and rural areas over time in the United States.28,29 Vital registration data can be standardized and harmonized to allow for cross-city comparisons, such as in the SALURBAL study that described within-country heterogeneity in life expectancy across Latin American cities.15\n\nA barrier to descriptive epidemiology in urban areas is that information is commonly collected to be representative of an administrative unit above the city (for example, of a state, province, or country). For example, the Global Burden of Disease project, which comprehensively describes the occurrence, mortality attributable to, and disability attributable to hundreds of diseases, injuries, and risk factors, presents information at the country level.30 Such comprehensive descriptive epidemiology does not exist for urban areas. Assuming 55% of the world’s population lives in urban areas1 and that there were 55.4 million deaths in 2019,31 then a crude calculation assuming the number of deaths in urban areas is proportional to their share of the population suggests about 30.5 million deaths (0.55*55.4 million) occurred in urban areas in 2019. Currently, only crude calculations such as this are available, and global estimates have not accounted for urban-versus-rural differences in mortality for reasons such as urban-rural differences in age structure or exposure to risks. The lack of urban-specific estimates of the health burden or of the scale of the health benefits that might result from relevant interventions poses challenges for allocating appropriate financial, institutional, and human resources to urban health action.\n\nWhile more work is needed to comprehensively describe the urban burden of ill health, existing information can serve as a useful guide. When direct measurement of health outcomes (e.g., through surveys) in cities is not feasible, two approaches hold promise for advancing descriptive epidemiology within and across urban areas: health-impact modeling and small-area estimation. Health-impact modeling is often used to project the health impacts of alternative scenarios. It can also be used to estimate the burden of dimensions of health attributable to the status-quo scenario. For example, health-impact modeling was used to estimate that exposure to air pollution among residents of 13,160 urban areas globally resulted in 1.8 million excess deaths in 2019.9 While valuable, health-impact modeling studies can rely on strong assumptions, for example that health effects estimated in one location can apply to the area of interest. As we discuss further below, health effects can be context-dependent.24 The validity of health-impact assessment may benefit from more explicitly considering the extent to which effects are transportable from one context to another.32\n\nAs health outcomes can vary considerably between and within urban areas,16 methods that aim to estimate health outcomes at a fine geographic scale are vitally important. Small-area estimation (SAE) is a suite of such methods. SAE methods estimate outcome measures (e.g., disease prevalence) at a unit of geography beneath the level where the measure is known (e.g., from a U.S. state to a county).33 SAE methods include, for example, non-parametric methods that use measured associations between the outcome and demographic characteristics at the larger geographic unit (e.g., U.S. states) and apply those associations to smaller units where the outcome is not measured (such as counties), spatial data smoothing, and regression techniques using area-specific data as predictors.33 Long used to estimate the prevalence of health-related behaviors at the U.S. county level,34–36 SAE methods have recently been used to estimate life expectancy of residents of U.S. census tracts (a within-city unit).37 Results suggest there is considerable variation in life expectancy between census tracts, underscoring that health varies within cities.38 An advantage of SAE methods is that they borrow information from the higher level, allowing investigations of small areas (such as an urban neighborhood) to use fewer resources than they might require if the higher-level information were not available. As with most any method, estimation relies on assumptions, for example, that the association between demographics and the outcome at the larger area holds at the smaller area. In the urban-health context, SAE methods may face particular challenges for key populations such as migrants or those who live in slums, groups whose health is difficult to measure.39,40 A small-area estimate aiming to estimate the health distribution of refugee settlements may be uninformative, for example, if it uses as key inputs the health distribution of surrounding areas, which may not be a strong predictor of the health of a group of individuals who recently arrived to that area.\n\n2.2.2 Describing the health-relevant context of urban areas\n\nDescriptive epidemiology conventionally measures health outcomes (such as cancer incidence and death) and individual-level risk factors (such as smoking and diet). As knowledge about the environmental impacts on health continues to grow, an increasingly important task for descriptive epidemiology, together with other disciplines, will be to better characterize the multi-level social and physical environments in urban areas that give rise to health.23,41 As an example addressing this need, a research coalition developed a dataset covering 371 cities in Latin America with various consistently defined indicators of the social environment across economic, social, housing, governmental, institutional, and organizational domains.41 They noted several challenges in developing this dataset including variation in data availability, quality, and spatial and temporal resolution and extent.\n\nThe surveillance of physical environmental conditions relevant for health has advanced considerably as data have become available from remote sensing (i.e., satellite imagery),42 street-level imagery (such as Google Street View),43 and open-source mapping software (such as OpenStreetMap).44 For example, remote sensing has been used to measure urban green space,45 street-view imagery to assess walkability and disorder of neighborhoods,43,46 and OpenStreetMap to assess building quality and attributes of the roadway network.44,47,48 One large-scale effort using some of these tools (OpenStreetMap, notably) is the creation of a multi-city dataset of livability indicators across several Australian cities.49,50 This dataset of Australian cities is impressive for its rich information about the physical urban environment at high (within-city) spatial resolution and the comparability of its measures between cities, as constituent cities are each measured using the same methods.\n\nAs illustrated by the creation of such large-scale multi-city datasets of the built environment, modern sources of street-level imagery and mapping software have eased the objective and harmonious assessment of the physical environment at scale. Challenges remain with their completeness, accuracy,48 and ongoing availability and legal use in urban health-related research.51\n\nRelated to the need for a consistent dataset of indicators of the social and built environment across and within cities is the need to systematically inventory policies, interventions, projects, and other actions that could affect these indicators. As Diez Roux writes, “Cities are acting,”2 but, generally speaking, the public health community lacks a robust system for collecting data on these actions. Some social health-relevant social policies, particularly those codified by law, have established databases tracking them.52 For example, databases on various social policies relevant for health have been documented, covering topics such as poverty and social welfare, firearms, alcohol, and tobacco.52,53 Other examples of health-relevant policy surveillance in the U.S. include monitoring of policies supportive of physical activity in the United States54 and of policies related to COVID-19.55 At the global level, the C40 Cities, a network of cities focused on climate-change action, have documented actions cities are implementing to adapt to climate change.56\n\nWork remains, however, in tracking the various actions—from formal legislation and regulation to local interventions—city governments and other actors are taking that could affect public health.57 Interventions and actions that occur beneath the city level can be particularly difficult to track systematically. Examples include the conversion of a vacant lot to housing, the construction of a neighborhood greenway, or the closing of a coal power plant. Epidemiologists, with expertise in counting and measurement across various scales of time and place, are well-suited to contribute to the surveillance of policies, interventions, and other population-level actions that could affect public health. Crowdsourcing this information may help.58 Critical data include where and when the action occurred, the geographic scale of the action, and, as applicable, the level of governance responsible.59 For evaluation purposes, documenting when the intervention occurred is especially important so that methods considering intervention timing (described in the next section) can be applied.\n\nAs well as a context in which population health manifests, cities and their characteristics are determinants and modifiers of health.3,21,60 The magnitude of ill health arising from urban determinants—or the potential health benefits from urban interventions—can be used to inform action that decision makers can take. Understanding how impacts vary by place, time, or other contextual factors can inform whether and how to tailor action to specific urban contexts. While there is a long tradition of theoretical and empirical research studying determinants of health at levels above the individual (such as the neighborhood, city, or institution),61–63 research is less robust on the effects of specific actions and policies taken by governments and other actors on health and health equity. Methods to study the longitudinal effects of group-level interventions, such as difference-in-differences, interrupted time series, and synthetic control methods,64,65 are well-suited for this purpose and have been used in recent years to study effects of policies and other actions between and within cities. When possible, these methods can take advantage of natural or quasi experiments.66 Some examples of their use in the urban-health context include an assessment of the effects of keeping indoor restaurant dining closed on COVID-19 rates in large U.S. cities,67 of a street-design intervention on pedestrian crashes in Mexico City,68 of bicycling infrastructure on bicycling levels in Atlanta, United States,69 and of a heat action plan on heat-related mortality in Montreal, Canada.70 Some of these tools allow for the estimation of place-specific effects which can inform the extent to which intervention effects are modified by context.71\n\nWhile these methods hold promise, they also bring about challenges for use in the urban-health context. One is that urban policies often co-occur,52,72 posing analytical challenges for isolating the impact of one specific action from another. Second, sometimes the area of interest has no suitable comparator over relevant characteristics, even when the comparator is a weighted average of several areas.73 This issue, sometimes called “non-positivity”, could arise in particular in unequal or segregated cities. A third is difficulty characterizing where to “draw the line” particularly for actions or events whose effects may be diffuse, such as wildfires or built-environment interventions.69,74,75 While these challenges warrant further attention, this family of methods is sufficiently well-developed to be useful in a range of urban settings for the evaluation of policies, actions, and climate-related events.74\n\nAbove, we noted that a challenge with some policy-evaluation methods is isolating specific effects in the context of other co-occurring interventions and actions.52 Perhaps more importantly, isolating specific effects may not always be the most useful question to answer if the goal is to improve population health.76 These conceptual and methodological challenges motivate calls to view urban interventions and actions as part of complex systems.27,76–78 Features of complex systems include multiple levels of organization, heterogenous units, dependencies between units, and feedback loops.24 In a review of public health interventions adopting a complex-systems perspective, the authors categorized the goals of such studies into five stages: theorizing, prediction, process evaluation, impact evaluation, and further prediction.79 Information derived from considering urban health as a complex system adds a new layer of value for policy-making beyond the burden of urban ill health and the health impacts of specific urban determinants and actions. Well-executed, a complex-systems approach can help policymakers understand tradeoffs, unanticipated effects, implementation challenges, the potential impact of multiple interventions, and other effects arising from urban complexity.\n\nPrediction (or simulation) is a common application of these complex-systems methods, the purpose of which is to “hypothesize and simulate how an intervention may impact on and interact with a complex system” or, similarly, to “hypothesize and simulate how agents within a complex system react and interact in response to an intervention.”79 Respectively, these two objectives roughly correspond to the approach of system dynamic models and agent-based models (ABMs).79 The strengths of these systems methods are that they allow the investigator to perform complex simulations of how an intervention may unfold, considering interactions, interdependencies, and feedback.\n\nABMs, in particular, have been explored for their potential to inform and evaluate interventions related to urban health.80 Authors exploring their utility and challenges have suggested that ABMs are attractive for three reasons. First, the method “… is well-suited for modeling exposure influenced by specific behaviors, their timing, and location.”80 Second, “any mathematical relationship— … non-linear, complex interactions—can be algorithmically modeled in an ABM.”80 Third, “ABMs can integrate many factors resulting in a holistic and context-dependent model.”80 ABMs also raise several challenges, however.80,81 One is that they require a rich evidence base to inform their models. Evidence does not always exist to inform the various steps of such models, requiring researchers to rely on strong assumptions, and erroneous assumptions may affect model behavior in complex ways. Existing epidemiological evidence may also have been conducted in populations whose distribution of key characteristics differs from that in which the model is to be applied. These challenges imply that it remains important to conduct traditional epidemiologic research to inform these systems models.\n\n\n3. Conclusions\n\nThe reviewed conceptual model considers various ways to understand—and even define—urban health. Within each conceptual frame, more work is needed to advance understanding of urban health and support action to improve the health of urban populations. For example, it is unknown how much ill health occurs in urban populations. In this article, we crudely estimated that about 30-35 million deaths occur annually in urban areas, but this estimate relies on strong assumptions and ought to be improved upon. More descriptive epidemiology is needed to characterize urban health with both fine (within-city) resolution and at a large (global) scale to better understand differences in health between and within urban areas. There is a need for improved measurements of both the health of urban populations and of the environments that give rise to health. Creating databases at the multi-city scale containing high-resolution indicators of the social and built environments and related policies, interventions, and other actions should be encouraged. Noted examples characterizing indicators and policies in Latin America41 and Australia49 may serve as a guide.\n\nThere is also a need to understand what works to improve urban health. Decades of research have shown links between social and physical urban environments and health, but research evaluating the impacts of actual actions (e.g., policies and interventions) that may affect urban health and health equity remains comparatively scarce. Monitoring actions between and within cities would enable such evaluations. Finally, the argument for considering the health effects of urban living as part of a complex system is persuasive,76 but our tools for quantitatively understanding these system-level processes remain under-developed in the public-health literature, in particular for the evaluation of urban-health interventions.79 That many of these systems modeling methods require information-rich empirical evidence also underscores the need for traditional epidemiologic research to inform their components. While it will take a multi-disciplinary effort to address these gaps in understanding, the discipline of epidemiology, specifically, can inform urban-health understanding by adopting a broad view of descriptive epidemiology that includes surveillance of the urban physical and policy environment, continuing to evaluate group-level interventions between and within urban areas, and advancing research on systems thinking in urban health issues.\n\nTo support this needed understanding, we recommend several actions that can be taken by stakeholders in national governments, local governments, not-for-profit organizations, coalitions, and academia. National governments could increase funding for fine-scale urban health surveys and surveillance systems and develop dashboards displaying resulting measures. One example in the U.S. context is the City Health Dashboard.82,83 As individual countries improve urban-health surveillance, the magnitude of urban-health challenges at the global or regional scale may become more apparent. Public health practitioners and other officials in local governments could similarly collect small-area health data and, ideally, present it in standardized formats on open-data portals.84 Local governments are especially well-suited to conduct policy surveillance on actions that could affect urban health, as they are often responsible for their on-the-ground implementation. If data collection on all relevant interventions and actions is not feasible for government officials, they could partner with academic researchers, not-for-profit organizations, or global coalitions such as C40.85 The evaluation of policies and interventions that could affect urban health at the local level is another area well-served by cross-sectoral collaboration. This collaborative evaluation research is particularly important in sectors not traditionally viewed under the public-health umbrella ranging from but not limited to transportation systems, housing policy, taxation policy, and energy systems. Throughout urban health surveillance and evaluation, care should be taken to collect data to represent marginalized groups and evaluate impacts on equity-related outcomes.",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\n\nAcknowledgments\n\nWe thank José Siri and Nathalie Roebbel for guidance on the structure and content of this article.\n\n\nReferences\n\nWorld Urbanization Prospects: The 2018 Revision. United Nations Department of Economic and Social Affairs, Population Division; Accessed May 18, 2023. Reference Source\n\nDiez-Roux AV: What Is Urban Health? Defining the Geographic and Substantive Scope.Lovasi GS, Diez Roux AV, Kolker J, editors. Urban Public Health: A Research Toolkit for Practice and Impact. Oxford University Press; 2020; pp. 3–26. Publisher Full Text\n\nVlahov D, Freudenberg N, Proietti F, et al.: Urban as a Determinant of Health. J. Urban Health. 2007; 84(S1): 16–26. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDiez-Roux AV: Global Urbanization and Health Trends.Lovasi GS, Diez Roux AV, Kolker J, editors. Urban Public Health: A Research Toolkit for Practice and Impact. 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}
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[
{
"id": "324311",
"date": "08 Oct 2024",
"name": "Alina Schnake-Mahl",
"expertise": [
"Reviewer Expertise social epidemiology",
"policy evaluation",
"urban health",
"health disparities"
],
"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 provides a structured framework for thinking about epidemiology and urban health, and opportunities for future epidemiologic work in this area. I commend authors for taking on the difficult but important task of outlining the epi case for urban health. The article is well organized, comprehensive, and provides a nice overview of current work. My suggestions are mostly small additions.\nCities and urban are used interchangeably- while other work such as the urban health textbook, have I believe worked to define these terms, it would be helpful to repeat or summarize the definition of urban and city for readers.\n\nThe sentence “ Variable exposure to environmental conditions (both social and physical) gives rise to health inequities in urban populations by characteristics such as income and wealth, residential neighborhood, race and ethnicity, age, disability, gender identity, sexual orientation, or migration status.16 “ seems to orient around individual level predictors of health inequities, rather than inequitable social, political, and environmental exposures as predictors of inequities. Both should probably be included.\nThough the section on small area estimates is within the descriptive epidemiology section, it’s important to add limitations of small area estimation for sub-unit evaluation of health changes over time, as the methods integrate sub-unit specific information and therefor shouldn’t be used for assessing changes or evaluating local intervention effects over time, and any use with modeling should incorporate the uncertainty estimates. See, for example the language on the CDC PLACES website about limitations of using the data. It may be worth mentioning potential of Bayesian methods for small areas as well?\nThe section on tracking policy would benefit from acknowledging and briefly describing legal epidemiology and policy surveillance methods as burgeoning and rigorous methods to track laws and policies over time. However, local policies are often difficult to track especially historically, despite resources such as Municode, in the United States, because local laws and policies are often unavailable on city or county websites or tracking sources. This is also a good opportunity to highlight the importance of interdisciplinary collaborations (e.g. with lawyers or policy experts) to identify, code, and interpret laws and policies, while bringing our epidemiologic focus on sources of bias, good coding and data management practices, and fascination with methodological rigor.\n\nSee for example (refer 1 and refer 2)\n\nThe paragraph on tracking policies would also benefit from citations focused on tracking city-level (or sub city-level) policies. Most of the citations are focused on state level (or multilevel – e.g. the matthay article) articles. Suggested citation:\nrefer 3\n\nIt would be helpful to allude back to the issue of lack of outcome data at the city or sub-city level for quasi-experimental evaluation. It would also be helpful to mention the importance of understanding effect modification within a city (e.g. by neighborhood SES or SVI) to monitor impacts of city level policies on disparities.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Yes\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? Yes",
"responses": []
},
{
"id": "337108",
"date": "21 Nov 2024",
"name": "Gregory Heath",
"expertise": [
"Reviewer Expertise Guerry Professor Emeritus in the Public Health and Medicine at the University of Tennessee Chattanooga and a former Lead Health Scientist/epidemiologist at the U.S. Centers for Disease Control and Prevention (CDC)",
"for over 20 years. A doctorate in physiology/nutrition and an MPH in epidemiology from the Loma Linda University School of Public Health. I have spent most of my career devoted to the epidemiology",
"prevention",
"and management of chronic diseases and their associated behavioral risk factors (e.g.",
"physical inactivity",
"poor diet",
"obesity). I am widely published in the preventive medicine and public health literature with an h-index of 65. I am a Fellow in the American College of Sports Medicine (ACSM) and the American Heart Association’s Council on Epidemiology and 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\nThe authors provide a good overview of the position that urban health is critical to global health particularly relative to emerging economies among low to middle income countries, where there is a significant shift in populations moving from rural to urban centers.\n\nThis is compounded by the existence of what is referred to as the epidemiologic transition from primarily infectious disease to non-communicable diseases (NCD) such as cardiovascular disease, T2DM, HTN, and their associated risk factors of obesity, physical inactivity, and unhealthy refined dietaries.\n\nThe authors appropriately identify the importance of descriptive epidemiology and public health surveillance to understand these population dynamics. Their emphasis on using such surveillance to track not only diseases and their biological risk factors but also policies and practices supporting environmental supports for healthy living within the context of the urban environment are key to protecting and promoting the health of urban populations. The paucity of such policy and practice surveillance is mentioned as a current deficiency within urban environments. Hence, the authors provide insights and a sense of urgency for the greater adoption of systems thinking in tackling urban population health, where intersectoral collaboration, coordination, and cooperation are currently often lacking both in intention and function.\n\nThe authors should cite additional sources of local health and policy data from the following sources:\nThe CDC Places data - that provides small area epidemiologic surveillance across sectors: https://www.cdc.gov/places/index.html\n\nAlso, the County Health Rankings published by the University of Wisconsin's Population Health Institute should also be cited: https://www.countyhealthrankings.org/\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Yes\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? Yes",
"responses": []
},
{
"id": "337107",
"date": "04 Dec 2024",
"name": "Simon Rüegg",
"expertise": [
"Reviewer Expertise Veterinary Epidemiology",
"Participatory Modelling",
"One Health",
"Knowledge Integration"
],
"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\nGiven that in the 21st century most of the global population is living in urban settings, the reflection on the importance and requirements of urban epidemiology are pertinent and timely. Particularly the geographic resolution is a hindrance in open sight which must be brought to the attention of policy makers and health agents. However, given the current polycrisis including climate change, biodiversity loss and pollution which are directly and indirectly affecting human health, the sole emphasis on human health indicators seems somewhat anachronistic and narrowly focused. The authors legitimately build on historic practices in epidemiology using the four framings of cities as contexts, as determinants, as causes of human health and as complex systems that shape health. I would find it interesting to differentiate somewhat more explicitly, which framing is useful for which kind of questions. Admittedly I am biased by a complexity approach to health. But I would advocate such an approach primarily for wicked health problems for which multiple aspects interact. Also, in the context of sustainable development participatory and complexity-aware approaches have shown to be more effective than linear analysis and intervention. There may however be public health related questions, e.g. health care infrastructure planning, which would benefit from a leaner and more data driven approach. I would welcome if the authors could include a reflection on the utility of framings in urban health decision making. Particular attention should be given to the ecological fallacy as populations are studied but individuals may participate in many populations and thus cumulate exposures or compensate them. This seems particular tricky if geographical approaches are used that do not include behavioural parameters. Many statements throughout the text and particularly section 2.4 seem to indicate that the authors acknowledge that cities are complex adaptive systems. This would imply that linear regression models and alike are tools that struggle to provide adequate information for decision making. This brings me to my main point of critique of the text in which I think, the field of medical epidemiology is well explored but expertise from ecology including its methods for analysis and modelling of complex ecosystems is largely missing. Secondly, in view of the polycrisis I would find it appropriate that urban health be concerned with other species than humans too, i.e. domestic animals, urban wildlife and plants, which in co-evolution and co-habitation with humans play a role in physical and mental human health but would also deserve some attention for their own sake. Understanding humans as part of nature and thus cities as dense ecosystems may shed some new understanding on public health issues, where species can co-benefit or co-suffer from exposures. A further point that may be explored is that surveillance should be retrofitted from the decision making process to provide the data that is needed to make informed decisions. Traditionally, we use available data to produce information. However, when complex systems are addressed, it becomes more important to identify and collect the data that is needed to observe and monitor health over time. Particularly, when health is co-constructed with citizens, it will require more and more varied data than the one we are used to collect in medical and health communities, which still rely largely on a deficit-oriented definition of health, i.e. absence of disease.\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/13-950
|
https://f1000research.com/articles/13-947/v1
|
21 Aug 24
|
{
"type": "Policy Brief",
"title": "A critical postmodernist evaluation of the policy responses to forced marriage in the UK",
"authors": [
"Aiyesha Swarnn"
],
"abstract": "This paper critically evaluates the UK’s policy responses to forced marriage through a postmodernist lens. Utilising data from the UK Forced Marriage Unit (FMU), which supported 302 cases in 2022 involving possible forced marriage or female genital mutilation, this paper highlights the complexity of addressing forced marriage as a human rights violation. To begin, the paper discusses three primary policy approaches employed by the UK in combatting forced marriages, which are regulation, exit, and community engagement. Through a postmodernist analysis, this paper critiques the essentialist view of forced marriage as a cultural problem and argues for a more nuanced understanding that incorporates diverse experiences and intersecting sociological, political, and economic factors. Due to this, this paper recommends removing forced marriage from the ‘honour-based abuse’ category and advocates for the implementation of reliable data-collecting methods to better address this issue.",
"keywords": [
"Forced Marriage",
"Postmodernism",
"Honour-based abuse",
"UK"
],
"content": "Introduction\n\nForced Marriage (FM) is defined as “where one or both people do not or cannot consent to the marriage and pressure or abuse is used to force them into the marriage” (Foreign, Commonwealth & Development Office (FCDO), 2023).\n\nIn 2022 alone, the FMU supported individuals in 302 cases related to possible FM or possible female genital mutilation (FGM) (FCDO and Home Office (HO), 2023a). Globally, the International Labour Organisation, Walk Free, and International Organisation for Migration (2022, p. 2) estimated that 22 million people in 2021 were in FMs. Given the increased prevalence of FMs globally, FM cases in the UK are expected to also increase. However, the 302 cases of FM in the UK indicate a 10% decrease compared to the 337 cases reported in 2021 (FCDO and HO, 2023a).\n\nDue to the amalgamation of FM and FGM data, it is impossible to know whether this 10% decrease in cases reflects a decrease in FMs across the UK. Thus making FM an underreported and hidden issue. FM violates human rights as it denies individuals the autonomy to choose their partners and enables control over an individual’s personal decisions (SafeLives, no date, p. 1). Therefore, this paper will employ the postmodernist perspective to understand individuals’ diverse experiences and language in shaping the FM reality. It will discuss the problem, policy responses, and recommendations based on research and individual experiences.\n\nFM became centralised on the UK policy agenda in 1998 after the high-profile murder case of Rukshana Naz, who resisted her FM (Anitha and Gill, 2023). Ruksana’s case helped launch an enquiry into FMs across the UK, leading to the formation of the FMU in 2005 (Foreign and Commonwealth Office, 2010, p. 4).\n\nDespite the establishment of the FMU, FM is framed as a cultural problem rather than, as postmodernists will claim, a socially created notion that is not an inherent or universally observed occurrence (Ida Bagus Weda, Grystin and Arif Sobirin, 2023). To illustrate, in 2022, the FMU handled cases in 25 focus countries (countries associated with the risk of FM), where Pakistan had a high number of FM cases, as seen in Figure 1 (Rights Lab, 2023, p. 6).\n\nThis figure illustrates the distribution of cases handled by the Forced Marriage Unit (FMU) across different focus countries in 2021 and 2022. The focus country is defined as the country to which the risk of forced marriage is prominent. This could be the country where the forced marriage is due to take place, the country where it has taken place, and/or the country where the spouse is currently residing. The figure shows the percentage of cases associated with each focus country for both years, highlighting the significant role Pakistan plays as a focus country in almost half of the cases.\n\nFigure 1 demonstrates that Pakistan was the ‘focus country’ in almost 50% of cases in 2021 and 2022. However, this data does not explain the reasons for such a high representation of FM cases in Pakistan and does not discuss the proportion of the total cases this represents.\n\nFurthermore, the classification of FM as a cultural problem is further exacerbated by the allocation of FM as a type of honour-based abuse (The Crown Prosecution Service, 2024), an umbrella term encompassing a range of offences in the name of honour (Aujla, 2021, p. 94). Due to this, feminist theorists have dominated the literature on FM and honour, as ‘honour’ is thus seen to reside in the objectification and control of women from honour cultures seen across Southeast Asia or the Middle East (Reddy, 2008). Although 235 cases (78%) of FM in 2022 involved women, 67 cases (22%) of FM involved men (FCDO and HO, 2023a).\n\nPostmodernists believe the feminist approach’s exclusion of men and diverse sexual orientations/backgrounds does not provide a complete picture of FM (Idriss, 2022). Therefore, it is crucial to acknowledge these varied experiences to transform FM into a socially constructed problem (Atabor, 2016). Describing FM as a ‘cultural’ problem asserts that FM has a particular essence of ‘culture’, which is necessary for determining the practice (Louis, 2014). Postmodernists critique this use of essentialism and argue that this viewpoint exhibits an oversimplified approach towards comprehending FM and hinders the efforts required to address the root cause (Louis, 2014).\n\nAccording to postmodernists, FM is caused by multiple intersecting factors that are not solely dependent on culture but by interlocking sociological, political, and economic disparities (Honkala, 2022, p. 473). When sexual orientation is questioned, FM can be used to force men or women into heterosexual marriages to discourage unfavourable relationships (Honkala, 2022).\n\nFM policy in the UK is initiated by the FMU (FCDO and HO, 2023b). According to Shariff (2012, p. 550), the unit’s FM policies have three target approaches:\n\n1. Regulation\n\n2. Exit\n\n3. Community Engagement\n\nRegulation is framed as safeguarding individuals to promote universal human rights. The FM (Civil Protection) Act 2007 is an example of this approach, as it offers civil action to protect individuals or individuals who may be susceptible to FM (Legislation.gov.uk, no date). Through this Act, individuals can apply for a FM Protection Order (FMPO). These legal orders are issued to prevent or halt the occurrence of FMs inside and outside of the UK, while ensuring continuous safeguarding for individuals who may be vulnerable to harm due to FM (HM Courts and Tribunals Service, 2020).\n\nSince 2014, the UK courts have granted 200-250 FMPOs annually, which are often deemed inadequate due to ineffective monitoring (Noack-Lundberg, Gill and Anitha, 2021, p. 371). This has led to numerous breaches of FMPOs, such as parents failing to comply with court orders or attempted circumvention of orders by applying for passports from other countries have occurred (Miles-Johnson and Courtenay, 2021).\n\nHowever, these breaches can be attributed to the court’s perception and reality of FM. As Berger and Luckmann (2011) mention, reality is socially constructed through the processes in which individuals and societies collectively attribute meaning and significance to phenomena. In this case, FM is determined by the term ‘consent’. In the UK legal context, consent is based on the ‘myth of free choice’ (Anitha and Gill, 2009, p. 174). This refers to the assumption that individuals have complete autonomy to consent to marriage without external pressures (Meyersfeld, 2011). Postmodernists argue that this is an oversimplified approach, as not everyone can consent to marriage due to and not limited to, violence, incapacitation, coercion and manipulation (Sandhu and Barrett, 2024).\n\nThe second approach, exit, empowers individuals to leave their cultural minority as their preferences cannot be realised (Shariff, 2012). An example of this approach is the Anti-Social Behaviour, Crime and Policing Act 2014, which criminalises FM under section 121 (HO, 2016). This policy reflects a concern for individual autonomy, which aligns with the postmodernist critique that challenges traditional power structures that may have allowed FM to occur (Barnard-Naudé, 2013). Although this policy can force individuals to choose between their culture and freedom, cultures are never fixed, closed or complete (Newman, 2005, p. 140). Cultural boundaries are constantly shifting, leading to new ways of thought in cultures, which can lead to acceptance (Newman, 2005, p. 140).\n\nFinally, the third approach is community engagement, which promotes intercultural dialogue with different communities. The ‘Right to Choose’ campaign, which involved short videos highlighting the devastating impact of FM, illustrates this approach (FCDO and HO, 2023c). This campaign was shared with communities across the UK, reflecting a departure from significant top-down approaches to a more participatory mode of engagement in combatting FMs (FCDO and HO, 2023c). However, this approach risks reinforcing power imbalances by granting excessive power to specific persons or groups claiming to speak for their community (Shariff, 2012, p. 550). This, as postmodernists would claim, perpetuates the idea that community groups are homogeneous, which fails to acknowledge the diversity and intricacy that exists within them (Dickerson, 2013).\n\nBased on the challenges mentioned in this paper, FM must be addressed with a coordinated strategy that acknowledges the intricate nature of this problem.\n\nI. The Removal of FM from the ‘Honour-Based Abuse’ Category\n\nThe removal of FM from the ‘honour-based abuse’ category is essential to recognise that FM is not a cultural problem but rather a socially constructed one. Postmodernists critique essentialist categories as they are inadequate in acknowledging the wide range of experiences within communities and can cause misclassification (Connell, 2005). FM can mistakenly be seen as just honour-based abuse, leading to underestimations or prevalence of this issue (Gill and Harvey, 2017). These categories can also perpetuate established power structures and promote misconceptions regarding specific communities. Therefore, removing FM from this category will allow policymakers to recognise FM as a distinct socially constructed issue with its unique circumstances and drivers.\n\nII. Implementation of Reliable Data-Collecting Methods and Protocols\n\nRemoving FM from the ‘honour-based abuse’ category eliminates the cultural connotations attached to the term, allowing for more precise FM data-collecting methods. Currently, FM data is fragmented as the data is mixed with the FGM data and is classified as ‘possible’ FM. Furthermore, there is little to no data on individuals who are LGBTQ+ or have disabilities and every year, the FMU receive referrals of FM from diverse sources, which can lead to inconsistencies in data (Aujla, 2021). In 2022, social services accounted for 24% of referrals, the police represented 15%, and education officials accounted for 9% (FCDO and HO, 2023a). Therefore, the creation of tailored data-collecting methods and protocols that address the frequency and causes of FM among different groups can adapt the current approaches to FM. This strategy should be adjusted to each source’s capabilities and resources.\n\n\nConclusion\n\nBy applying the postmodernist perspective in this paper, we can understand the FM reality built upon ‘consent’ and ‘culture’, which has shaped the UK’s policy responses to this issue through regulation, exit, and community engagement. Even though the policy responses provide a good starting point, there is a need to redefine FMs as a socially constructed problem to account for individuals who are not women or heterosexual. Moreover, due to limited space, this paper did not analyse the broader factors of religion and disability in conceptualising the FM narrative. Therefore, additional research is necessary to comprehend this topic thoroughly.",
"appendix": "Data availability\n\nThe data for this article consists of bibliographic references, which are included in the Reference section.\n\n\nReferences\n\nAnitha S, Gill A: Coercion, Consent and the Forced Marriage Debate in the UK. Feminist Legal Studies. 2009; 17(2): 165–184. Publisher Full Text\n\nAnitha S, Gill A: Understanding Protection and Prevention Responses to Forced Marriage in England and Wales.2023. (Accessed: 15 April 2024). Reference Source\n\nAtabor AA: Postmodernism and objectivity in the social sciences: redressing Nweke’s understanding of Atabor. Filosofia Theoretica. 2016; 4(2): 90–94.\n\nAujla W: Police understandings of and responses to a complex vignette of “honour”-based crime and forced marriage. International Journal of Child, Youth & Family Studies. 2021; 12(1): 93–123. Publisher Full Text\n\nBarnard-Naudé J: Of Dorothy’s Dog, ’Poststructural’ Fairy Tales … and the Real: Power, Poverty and the General Principles of the South African law of Contract. South African Journal on Human Rights. 2013; 29(3): 467–480. Publisher Full Text\n\nBerger PL, Luckmann B: The Social Construction of Reality: A Treatise in the Sociology of Knowledge. New York: Open Road Integrated Media; 2011.\n\nConnell RW: Masculinities. Cambridge: Polity; 2005.\n\nDickerson V: Patriarchy, Power, and Privilege: A Narrative/Poststructural View of Work with Couples. Family Process. 2013; 52(1): 102–114. PubMed Abstract | Publisher Full Text\n\nForeign and Commonwealth Office: The Right to Choose: Multi-agency statutory guidance for dealing with forced marriage.2010. (Accessed: 28 March 2024). Reference Source\n\nForeign, Commonwealth & Development Office: Forced marriage. 2023.(Accessed: 25 March 2024). Reference Source\n\nForeign, Commonwealth & Development Office and Home Office: Official Statistics: Forced Marriage Unit Statistics 2022.2023a. (Accessed: 25 March 2024). Reference Source\n\nForeign, Commonwealth & Development Office and Home Office: Multi-agency statutory guidance for dealing with forced marriage and multi-agency practice guidelines: Handling cases of forced marriage (accessible version).2023b. (Accessed: 3 April 2024). Reference Source\n\nForeign, Commonwealth & Development Office and Home Office: Forced marriage.2023c. (Accessed: 3 April 2024). Reference Source\n\nGill AK, Harvey H: Examining the Impact of Gender on Young People’s Views of Forced Marriage in Britain. Feminist Criminology. 2017; 12(1): 72–100. Publisher Full Text\n\nHM Courts & Tribunals Service: Forced marriage protection orders.2020. (Accessed: 3 April 2024). Reference Source\n\nHome Office: Policing and Crime Bill: Anonymity for victims of forced marriage.2016. (Accessed: 3 April 2024). Reference Source\n\nHonkala N: “An Unhappy Interlude”: Trivialisation and Privatisation of Forced Marriage in Asylum-Seeker Women’s Cases in the UK. Refugee Survey Quarterly. 2022; 41(3): 472–497. Publisher Full Text\n\nIda Bagus Weda W, Grystin DS, Arif Sobirin W: Social Studies In The Postmodernism Era. Technium Social Sciences Journal. 2023; 49(1): 158–165. Publisher Full Text\n\nIdriss MM: Abused by the Patriarchy: Male Victims, Masculinity, “Honor”-Based Abuse and Forced Marriages. Journal of Interpersonal Violence. 2022; 37(13-14): NP11905–NP11932. PubMed Abstract | Publisher Full Text | Free Full Text\n\nInternational Labour Organisation (ILO), Walk Free, and International Organisation for Migration (IOM): Global Estimates of Modern Slavery: Forced Labour and Forced Marriage.2022. (Accessed: 30 April 2024). Reference Source\n\nLegislation.gov.uk: Forced Marriage (Civil Protection) Act 2007.no date. (Accessed: 3 April 2024). Reference Source\n\nLouis A: Ethnicity and the Rhetoric of Essentialism in Philip Roth’s Operation Shylock. Critique - Bolingbroke Society. 2014; 55(4): 452–464.\n\nMeyersfeld B: Forced and servile marriage: a proposal for law reform in the Commonwealth. Commonwealth Law Bulletin. 2011; 37(4): 645–659. Publisher Full Text\n\nMiles-Johnson T, Courtenay T: Recognition and response: policing ’Forced marriage’ in England. Policing & Society. 2021; 31(10): 1248–1264. Publisher Full Text\n\nNewman S: Power and politics in poststructuralist thought: new theories of the political. London: Routledge; 2005.\n\nNoack-Lundberg K, Gill AK, Anitha S: Understanding forced marriage protection orders in the UK. The Journal of Social Welfare and Family Law. 2021; 43(4): 371–392. Publisher Full Text\n\nReddy R: Gender, Culture and the Law: Approaches to ‘Honour Crimes’ in the UK. Feminist Legal Studies. 2008; 16(3): 305–321. Publisher Full Text\n\nRights Lab: Briefing: The Forced Marriage Unit’s 2022 Statistics.2023. (Accessed: 20 April 2024). Reference Source\n\nSafeLives: Practice briefing: Identifying and engaging with young people at risk of forced marriage.no date. (Accessed: 30 April 2024). Reference Source\n\nSandhu KK, Barrett H: Girls just wanna have fun! South Asian women in the UK diaspora: Gradations of choice, agency, consent and coercion. Women’s Studies International Forum. 2024; 102: 102859. Publisher Full Text\n\nShariff F: Towards a Transformative Paradigm in the UK Response to Forced Marriage: Excavating Community Engagement and Subjectivising Agency. Social & Legal Studies. 2012; 21(4): 549–565. Publisher Full Text\n\nThe Crown Prosecution Service: So-Called Honour-Based Abuse.2024. (Accessed: 28 March 2024). Reference Source"
}
|
[
{
"id": "328527",
"date": "24 Oct 2024",
"name": "Brigitte Clark",
"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\nThis paper evaluates the UK’s policy responses to forced marriage, critiquing this policy from a postmodernist perspective and emphasising the challenge of dealing with forced marriage as a human rights violation. Forced marriage (FM) is defined as a situation “where one or both people do not or cannot consent to the marriage and pressure or abuse is used to force them into the marriage”. FM has been framed by the UK Government as a cultural problem and a type of honour-based abuse. This paper critiques this view of forced marriage as a cultural problem and argues for a more nuanced understanding that incorporates diverse experiences and intersecting sociological, political, and economic factors. The paper rightly points out that this approach may be over-simplistic and may exclude men and those of different sexual orientations. Postmodernists would argue that FM is caused by multiple intersecting factors that are not solely dependent on culture but by interlocking sociological, political, and economic disparities. The paper describes the FM policy in the UK as operating with three targets – ‘regulation, exit and community engagement’. The FM (Civil Protection) Act 2007 is offered as an example of the regulation approach, as it offers civil action to protect individuals or individuals who may be susceptible to FM with ‘consent’ as the central issue based on the ‘myth of free choice’ which fails to perceive the complexity of such situations where some persons may be coerced into marriage through many different reasons such as threat of violence, incapacitation, coercion and manipulation. The ‘exit’ approach, as exemplified by the Anti-Social Behaviour, Crime and Policing Act 2014 criminalises FM and may force individuals to choose between their family, culture and freedom. Finally, the third approach of ‘community engagement’ arguably perpetuates the idea that community groups are homogeneous. A critical postmodernist evaluation of the policy responses to forced marriage in the UK involves examining how these policies reflect broader societal narratives, power dynamics, and the complexities of identity. Postmodernism emphasises the role of language and discourse in shaping an understanding of social issues. In this regard, the term \"forced marriage\" has a certain meaning which may hide how coercion operates in subtle way in all communities and is thus not simply a cultural issue. The paper points out that the amalgamation of the FM and FGM statistics by the UK made it impossible to clearly distinguish between FM and female genital mutilation. Positioning forced marriage primarily as a cultural issue allows the law to overlook other social problems such as intersectionality which may affect consent. The paper recommends removing forced marriage from the ‘honour-based abuse’ category and advocates for the implementation of reliable data-collecting methods to better address this issue to recognise that FM is not a cultural problem but rather a socially constructed one. Removing FM from the ‘honour-based abuse’ category eliminates the cultural connotations attached to the term, allowing for more precise FM data-collecting methods. Currently, FM data is fragmented as the data is mixed with the FGM data and is classified as ‘possible’ FM. Furthermore, there is little to no data on persons with disabilities and additional research is also necessary, not only on the role of culture and the nature of consent, but also on religion and disability to comprehend this topic thoroughly. These arguments presented in this paper are based on a postmodernist epistemology and a certain formulation of justice. The contention that a postmodern perspective is more responsive to the complexity of what is being addressed acknowledges the gap between positive law and substantive justice. This could be diminished by greater political engagement.\n\nThe paper offers methods of interpretation which are both politically engaged and transformative. Policies should be responsive to the needs of those affected and be able to assess the efficacy of policy. The recommendations made by the paper are supported by the jurisprudential and practical arguments made.\n\nDoes the paper provide a comprehensive overview of the policy and the context of its implementation in a way which is accessible to a general reader? Yes\n\nIs the discussion on the implications clearly and accurately presented and does it cite the current literature? Partly\n\nAre the recommendations made clear, balanced, and justified on the basis of the presented arguments? Yes",
"responses": []
},
{
"id": "328531",
"date": "24 Oct 2024",
"name": "Margaret E Greene",
"expertise": [],
"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 paper addresses the important issue of how forced marriage is treated by policy in the UK context.\nIn my view, the writing in the paper needs strengthening. Its weakness and elisions may result in part from the effort to compress a complex and nuanced discussion into a brief document with a limited word count. Examples include:\nMuch is obvious to the writer that is not fully presented in the brief. What is the FMU referred to in the first paragraph? “Due to the amalgamation of FM and FGM data, it is impossible to know whether this 10% decrease in cases reflects a decrease in FMs across the UK. Thus making FM an underreported and hidden issue.” “Amalgamation”? The phrase starting with “thus” is not a sentence. Does this or doesn’t it show a decrease, which is what is asserted in the last sentence of the first paragraph? The arguments are poorly sequenced. The author uses odd wordings such as, “FM became “centralized” on the policy agenda” – not exactly sure what this means. The author’s interpretation of postmodernism is never provided, simply assumed. “the 302 cases of FM in the UK indicate a 10% decrease compared to the 337 cases reported in 2021 (FCDO and HO, 2023a).” Not sure it is reasonable to assume that this trend\n\nDoes the paper provide a comprehensive overview of the policy and the context of its implementation in a way which is accessible to a general reader?\nI think this “brief” is not a good format for such a complex issue, given the arguments the author wants to make. Why does the establishment of the FMU imply something other than a cultural framing? “Despite the establishment of the FMU, FM is framed as a cultural problem rather than, as postmodernists will claim, a socially created notion that is not an inherent or universally observed occurrence.” – why “despite”? “Postmodernists believe the feminist approach’s exclusion of men and diverse sexual orientations/backgrounds does not provide a complete picture of FM (Idriss, 2022).” Who says this exclusion is “the feminist approach”? The graphic is not useful for showing change, and change one year to the next is not that interesting anyway. Is this a real trend we’re seeing? The descriptions of the three components of the policy could be strengthened. How are people “empowered to leave their cultural minority”? What does this really mean?\n\nIs the discussion on the implications clearly and accurately presented and does it cite the current literature?\nThe paragraph beginning “Despite the establishment of the FMU…” is key, but is hard to understand Feminist interpretation of forced marriage is aligned with instances where men whose sexual orientation is in question are forced into marriage, and it offers an understanding of how patriarchy harms many in society. The author attempts to make a critique on the basis of the argument presented in Idriss, but without sufficient additional evidence.\n\nAre the recommendations made clear, balanced, and justified on the basis of the presented arguments?\nThe recommendations arrive when the elements of the policy have just been described. As a socially constructed issue, how is FP “distinct”? Data collection does sound inconsistent and haphazard. But doesn’t more need to be known regardless of whether the policy remains in place or not? I did not see in this paper any reference to FMs being about women/heterosexual women only, and I don’t understand why “consent” and “culture” preclude the variability in perspective the author is working to promote.\n\nIn sum, I think the author has identified an interesting topic, and has some good observations, but they are not sharp or sequenced or expressed well enough to make the case.\n\nDoes the paper provide a comprehensive overview of the policy and the context of its implementation in a way which is accessible to a general reader? Partly\n\nIs the discussion on the implications clearly and accurately presented and does it cite the current literature? Partly\n\nAre the recommendations made clear, balanced, and justified on the basis of the presented arguments? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-947
|
https://f1000research.com/articles/12-546/v1
|
24 May 23
|
{
"type": "Study Protocol",
"title": "Evaluation and comparison of the effectiveness of kaleidoscope and virtual reality goggles to reduce dental anxiety in young children undergoing administration of local anesthesia.",
"authors": [
"Himani Parakh",
"Nilima Thosar",
"Nilima Thosar"
],
"abstract": "Administration of local anesthesia via injection is the main reason for inducing anxiety in children and if not intervened it aggravates the anxiety in subsequent appointments. There are many approaches, including pharmacological and non-pharmacological methods that can be used to reduce children's perception of pain and anxiety. A frequently used non-pharmacological behaviour management method to reduce anxiety and procedure pain is distraction. The rationale of distraction is to shift the attention to avert the brain from receiving unwanted stimulus which induce anxiousness. Many approaches including music, television, portable video games, virtual reality (VR) helmet, and virtual reality audio-visual eyewear, have been implemented so far. Kaleidoscope and virtual reality goggles may help as distraction techniques in reducing the levels of anxiety caused during administration of local anesthesia. By the aid of which the operator may be able to make the dental experience child friendly and ultimately provide quality dental care to anxious children. Non pharmacological measures of reducing pain are cost effective and best means that can be used while performing dental procedures. This is a research protocol for a study aimed to evaluate and compare the effectiveness of kaleidoscope and virtual reality goggles to reduce dental anxiety in young children.",
"keywords": [
"Kaleidoscope",
"Virtual Reality",
"Distraction",
"Local anaesthesia",
"Young children"
],
"content": "Introduction\n\nAnticipation of pain during dental treatment is a frequently reported reason for dental anxiety and fear. Dental anxiety comprises of various physical, mental as well as social components. Anxiety has been defined as a “vague, unpleasant feeling accompanied by a premonition that something undesirable is about to happen”.1 In the terms of Dental Fear and Anxiety (DFA), Dental anxiety is characterized as significant negative or unpleasant feeling about a dental office and dental procedures; whereas dental phobia is an irrational form of dental anxiety.2 Dental anxiety is said to be a major contributor to poor oral health. Several studies have shown that the majority of significant triggers come from the sight, sound, and vibratory sensation of dental drills, and sensation of a local anaesthetic injection which is a major cause; subsequently dental fear is associated with past painful experiences and negative staff behaviour.3 An anxious patient is in a continuous state of restlessness and unease. Children experiencing anxiety during local anesthesia injection gives rise to a significant concern which thus necessitates cognitive - behavioural psychological guidance along with the needed dental treatment.4 There are many approaches, including pharmacological and non-pharmacological methods that can be used to reduce children’s perception of pain and anxiety.5,6 Amongst which the procedures that focuses on cognitive or behavioural methods include practices such as listening to music, dreaming, hypnosis, use of virtual reality goggles, progressive muscle relaxation, and distraction through various interventional techniques.7 Attention refers to focusing and processing information from our surroundings. While in anxious state it is important to shift the child’s attention away from the unpleasant stimuli. Distraction works on the principle of diverting the focus and blocking the reception of the unpleasant stimuli that causes anxiety.\n\nKaleidoscope is an instrument that shows an infinite number of fascinating geometric shapes in the form of a flower, repeating and reflecting images of coloured goggle fragments in the front section in a prism mirroring the inner surface. Increased blinking of the eyes is directly proportional to task difficulty, which in turn produces stress. In a relaxed situation, such as during kaleidoscope viewing, the number of blinks decreases and thus it controls the general physiological excitation.8,9 Kaleidoscope is being increasingly recognized for its therapeutic and healing value in medical procedures but very few studies on it are available for its use in pediatric dentistry.\n\nVirtual Reality (VR) is a human–computer interface that enables the user to communicate with the computer-generated atmosphere with dynamism. VR actively involves children and is a potent tool in helping children to keep their attention away from frightening and painful procedures. It allows the children to perceive the environment as a safe where they can be free without any risk.10,11\n\nHence the focus of this study, according to the available literature, is to evaluate and compare effectiveness of kaleidoscope and virtual reality goggles to reduce dental anxiety in young children.\n\nThe aim of this study is to evaluate and compare the effectiveness of kaleidoscope and virtual reality goggles to reduce dental anxiety in young children undergoing administration of local anesthesia.\n\nObjectives are:\n\n1. To evaluate the effect of kaleidoscope to reduce dental anxiety levels in young children before and after the administration of local anesthesia.\n\n2. To evaluate the effect of virtual reality goggles to reduce dental anxiety levels in young children before and after the administration of local anesthesia.\n\n3. To compare effect of kaleidoscope and virtual reality goggles technique to reduce dental anxiety levels in young children before and after the administration of local anesthesia.\n\nThis randomized clinical trial will be conducted in an isolated setup over a period of six months. Children from five - eight years old who are healthy, co-operative but anxious and children undergoing dental treatment requiring administration of local anesthesia will be included in the study. Children with known vision problems, psychological abnormalities, children with special health care needs, children suffering from systemic diseases and the parents that are unwilling to participate will be excluded from the study.\n\nGroup 1 – Kaleidoscope: The children will be given a kaleidoscope having various changing colours and patterns to watch through just before the starting of the procedure and will be asked to watch through it until the procedure ends.\n\nGroup 2 – Virtual reality goggles technique: The children will be asked to wear Virtual Reality goggles and a video to keep the child engaged will be played by clicking on the remote control. VR will be given just before the starting of the procedure and will be asked to watch through it until the procedure ends.\n\nGroup 3 – Control group wherein no such distraction technique will be employed.\n\nIt is a randomized clinical trial. This is a version 1 of the protocol. Sequence generation by lottery method will be generated. The co-investigator of the department will generate the allocation sequence and will assign participants to interventions. Trial participants, data analysts will be blinded. Data management by double data entry will be done. Personal information about potential and enrolled participants will be collected and maintained in order to protect confidentiality before, during, and after the trial. Comparators Kaleidoscope, Virtual reality goggles technique and conventional behaviour management method will be taken into consideration for comparing as all of them are interventions aiding for reducing the anxiety levels.\n\nThe sample size calculation is based on previous research that used a similar study technique and by using the sample size formula for difference between two means, zα+zβ2δ12+δ2/k2∆2.\n\nA total of 60 children will be included for the study. The participants in each group will be selected by simple random sampling method.\n\nVFAS score using Visual Facial Anxiety Scale is the primary outcomes to be measured. Pulse oximeter to measure physiological signs of oxygen saturation, and pulse rate, respiratory rate are the secondary outcomes to be measured. All the outcomes will be measured before, during and after intervention.\n\nAnalytical tests like Chi square test and student’s t-test will be performed. All the statistical analysis will be performed using SPSS software, version 27.0 p<0.05 will be considered as the level of significance. This randomized clinical trial will be conducted at the Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College, Datta Meghe Institute of Higher Education and Research, Wardha. The allocation will be done using lottery method.\n\nOnce completed the study will be published in a PubMed, Scopus indexed journal.\n\n\nDiscussion\n\nThere is a limited literature available regarding the use kaleidoscope as a distraction method for children undergoing dental procedures. Aditya et al. conducted a study to compare various methods of distraction to control anxiety in 60 children between the age group of six - nine years divided into four groups. Group 1 was fidget spinner (FS), Group 2 was kaleidoscope, Group 3 Virtual reality and Group 4 was control group with no distraction. The child’s self-reported anxiety levels using Venham’s picture test (VPT); the pulse oximeter was used to measure physiological signs of oxygen saturation and pulse rate at three intervals i.e. before, during, and after the IANB procedure. The VPT values were lower in the first three groups. Hence it was concluded that Fidget spinner, kaleidoscope, and virtual reality seem to be effective distraction methods and can be recommended as effective approaches to help reduce children’s dental anxiety during IANB procedures.12 Tailor et al. found out that when Virtual reality (VR) and on-screen audio-visual distraction techniques were used in the age group of 4-8 years the VPT scores were significantly reduced in VR group as compared to On-screen aid group in the first two visits that included procedures of screening, cavity preparation and L.A. administration.13 The effect of cartoon display and kaleidoscope in children between the ages of 5-12years was assessed and the anxiety levels were scored using Children’s Fear Scale by Molu and Açıkgöz, during echocardiography procedure. A significant difference is evident in anxiety scores before and during between all the intervention groups and it was concluded that use of kaleidoscope is an effective measure in reducing anxiety.14 Distraction by Kaleidoscope and VR is a promising area for future research in pediatric dentistry because of the rising interest in non-pharmacological methods for behaviour management.\n\nEthical approval for the study was obtained from the Institutional ethics committee of Datta Meghe Institute of Medical Sciences (Deemed to be University) [ref no: DMIMSU (DU)/IEC/2022/756].\n\nThe study protocol will be explained to the participating children and their parents.\n\nFurther, a written informed consent will be obtained from their parents.\n\nTrial Registration is done under The Clinical Trials Registry - India, the registry number is (CTRI/2023/04/051258- REF/2023/03/065058)\n\nDate of Registration: 03/04/2023\n\nhttps://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=83188&EncHid=56660.93573&modid=1&compid=19\n\nYet to be started.",
"appendix": "Data availability\n\nNo data is associated with this article.\n\nZenodo. SPIRIT checklist for “Evaluation and comparison of the effectiveness of kaleidoscope and virtual reality goggles to reduce dental anxiety in young children undergoing administration of local anesthesia”. DOI: https://doi.org/10.5281/zenodo.7811753\n\n\nReferences\n\nHare J, Bruj-Milasan G, Newton T: An Overview of Dental anxiety and the non-pharmacological management of dental anxiety. Prim. Dent. J. 2018; 7(4): 36–39. Publisher Full Text\n\nPorritt J, Buchanan H, Hall M, et al.: Assessing children’s dental anxiety: a systematic review of current measures. Comm. Dent. Oral Epidemiol. 2013; 41(2): 130–142. PubMed Abstract | Publisher Full Text\n\nOosterink FMD, de Jongh A , Aartman IHA: What are people afraid of during dental treatment? Anxiety-provoking capacity of 67 stimuli characteristic of the dental setting. Eur. J. Oral Sci. 2008; 116: 44–51. Publisher Full Text\n\nArmfeild JM, Milgrom P: A clinician guide to patients afraid of dental injections and numbness. SAAD Dig. 2011; 27: 33–39.\n\nCarlsson SG, Wide Boman U, Lundgren J, et al.: Dental anxiety – a joint interest for dentists and psychologists. Eur. J. Oral Sci. 2013; 121: 221–224. Publisher Full Text\n\nUman LS, Birnie KA, Noel M, et al.: Psychological interventions for needlerelated procedural pain and distress in children and adolescents. Cochrane Database Syst. Rev. 2013; CD005179. Publisher Full Text\n\nOzveren H: Non-pharmacological methods at pain management. Hacettepe University Faculty of Health Sciences. Nurs. J. 2011; 83e92.\n\nKoç Özkan T, Polat F: The Effect of Virtual Reality and Kaleidoscope on Pain and Anxiety Levels during Venipuncture in Children. J. Perianesth. Nurs. 2020 Apr; 35(2): 206–211. Publisher Full Text\n\nCanbulat N, Inal S, Sönmezer H: Efficacy of distraction methods on procedural pain and anxiety by applying distraction cards and kaleidoscope in children. Asian Nurs. Res (Korean Soc Nurs Sci). 2014 Mar; 8(1): 23–28. PubMed Abstract | Publisher Full Text\n\nCarmona Torres JA, Cangas Diaz AJ, Langer Herrer AI: Applications of 3D Simulation in Mental Health: Utilities and New Developments. Mental Illnesses - Evaluation, Treatments and Implications. 2012. Publisher Full Text\n\nÖzalp Gerçeker G, Ayar D, Özdemir EZ, et al.: Effects of virtual reality on pain, fear and anxiety during blood draw in children aged 5–12 years old: A randomized controlled study. J. Clin. Nurs. 2019; jocn.1517.\n\nAditya PVA, Prasad MG, Nagaradhakrishna A, et al.: Comparison of effectiveness of three distraction techniques to allay dental anxiety during inferior alveolar nerve block in children: A randomized controlled clinical trial. Heliyon. 2021 Sep 29; 7(9): e08092. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTailor B, Bargale S, Dave BH, et al.: Comparison of Virtual Reality Glasses vs On-screen Distraction Technique in Reduction of Pediatric Dental Anxiety: An in vivo Study. J. South Asian Assoc. Pediatr. Dent. 2021; 4(1): 22–26.\n\nMolu B, Açıkgöz A: A randomized controlled study: The effect of preprocedurals ınformative animation watch about echocardiography and ıntraprocedural kaleidoscope watch on anxiety in children. Jpn. J. Nurs. Sci. 2022 Apr; 19(2): e12468. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "197357",
"date": "15 Sep 2023",
"name": "Rekhalakshmi Kamatham",
"expertise": [
"Reviewer Expertise Pediatric dentistry- Behavioral management",
"Biostatistics"
],
"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 interesting protocol. The literature on the comparison of kaleidoscope and virtual reality to reduce dental anxiety in young children is meager. However, there are certain flaws in the methodology:\nAuthors failed to mention the type of randomized clinical trial and the trial design; whether it is superiority, inferiority or equivalence trial; whether it is parallel or split mouth.\n\nCan elaborate on the inclusion criteria like the procedures that the authors want to consider.\n\nControl group intervention should be modified to usage of basic behavior guidance techniques. We feel it is not proper to mention no such distraction technique.\n\nAuthors can consider other validated outcome measures to assess the anxiety in the children of the considered age group. Please mention whether the visual facial anxiety scale is validated or not. Should clearly mention the primary and secondary outcome measures.\n\nThe sample size determination is not correct. What is the study that the authors have considered for sample size determination?\n\nThe authors have wrongly mentioned simple random sampling method. It should not be a sampling method!! Need to modify the randomization, sequence generation methods.\n\nWhat about blinding? Authors did not mention about blinding aspect.\n\nWhat is the use of Chi square test? Please describe in detail the application of each test.\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": [
{
"c_id": "10823",
"date": "18 Jun 2024",
"name": "Himani Parakh",
"role": "Author Response",
"response": "Thank you for your valuable suggestions. I have made the corrections in the manuscript regarding the type of randomization, refinement of the inclusion criteria, and outcome measures. Sample size calculation based on key articles is updated. Information about blinding is available in the protocol section of the manuscript. To test the null hypothesis, I would like to add that the Chi-square test will be applied as the sample size is more than 30. I have uploaded the version 2 with all the modifications as quoted."
}
]
}
] | 1
|
https://f1000research.com/articles/12-546
|
https://f1000research.com/articles/13-945/v1
|
21 Aug 24
|
{
"type": "Research Article",
"title": "Reformulation of Policies to Prevent Land Conversion of Rice Fields In Achieving Indonesia's National Food Security",
"authors": [
"saeful kholik",
"Ida Nurlinda",
"Zainal Muttaqin",
"Maret Priyanta",
"Ida Nurlinda",
"Zainal Muttaqin",
"Maret Priyanta"
],
"abstract": "Background Increased population growth and imbalance between the need for rice are driving the conversion of numerous rice fields into non-agricultural zones and posing a significant threat to national food security. Therefore, this research is carried out to effectively address Indonesian government’s policy in preventing conversion of rice fields due to the lack of harmonization between cross-sectoral policies.\n\nMethod A juridical-normative research method is used to analyze policy problems through legal theory and reality. The method is studying regulations against social phenomenon in food security sourced from the unconformity between the policies and the reality. It started by elaborating a way of thought, synthesizing conclusions, stating errors, and advising the re-formulation of policies to change the appropriation of land that in turn will affect national food security.\n\nResults The results show that there is proposed concept for reformulating rice field policies to integrate policies across sectors, ensure coherence in policy planning, and enhance the efficiency policies. The addition and harmonization of the components will strengthen the protection of the rice fields while preventing inconsistency and overlapping of authority from different sectors. The realization of this re-formulation will in time manifest national food security.\n\nConclusions Indonesian government stipulates various policies to prevent the conversion of rice fields and to manifest national food security. However, of inconsistency and overlapping authority persist in its practice. Further close examination and reviews show the need reformation of policy for a transfer of land appropriation.",
"keywords": [
"Policy",
"Reformulation",
"Food Security"
],
"content": "Introduction\n\nThe designation of spatial planning is not an important factor in altering land ownership rights. In this context, land holds the potential for achieving prosperity, but the tendency of use is not consistent with the country’s vision. Therefore, the participation, understanding, and awareness of the community become crucial indicators in realizing spatial planning, which indirectly contributes to national food security. A land reform policy is an implementation of Law Number 5 of 1960 concerning Basic Agrarian Principles in prioritizing aspects of national food self-sufficiency (Fadjar et al., 2017). Another objective of land reform is to eliminate disparities in rights and ownership to transform living patterns to be more effective, productive, and sustainable. To optimize the concept of agrarian renewal, principles serving as the foundation and guidance for the implementation are required. These principles should be holistic, comprehensive, and capable of including essential aspects. Article 4 of the Decree of the People’s Consultative Assembly No. IX/MPR/2001 regarding agrarian renewal and natural resource management establishes 12 principles of agrarian renewal.\n\nAgrarian renewal in the decree of the People’s Consultative Assembly states that the principles serve as a reference in the drafting of various resource management regulations. This necessitates efforts to reassess and harmonize various sectoral regulations, which may include the repeal, replacement, or refinement of sectoral laws in the agrarian field. According to Maria S.W. Sumardjono, the principles of agrarian renewal should be accommodated as the basis for achieving the welfare of the people when considering the direction of development policies (Ida Nurlinda, 2009).\n\nA form of implementing national food self-sufficiency is by protecting paddy fields from being converted into non-agricultural land (Arnowo, 2022). Conversion is a factor contributing to the reduction in the availability of rice. High levels of development activities and population growth have led to increased land demand, while the availability and size of paddy fields remain relatively unchanged. In addition, conversion at a rate of 100,000 to 150,000 hectares per year outweighs the establishment of new paddy fields, which is only around 60,000 hectares per year and the impact includes various extensive interests, including:\n\na. Threatening the sustainability of food self-sufficiency.\n\nb. Reduce labor absorption.\n\nc. Waste of government investment, both central and regional.\n\nd. Reducing the quality of the environment.\n\ne. Disrupting the stability of the social structure of society.\n\nBeside population growth and insufficient availability of paddy fields, these issues are related to LSD, often repurposed for cultivation other than agricultural purposes. In Regency Bandung, some areas are required for national strategic project (PSN) of the Jakarta-Bandung high-speed train. This practice poses a risk in spatial planning administration, leading to economic development within areas designated for sustainable agricultural food zones. Therefore, it contributes to the expansion of non-agricultural land use activities, contrary to LP2B designation, which aims to protect and develop land (Angraini et al., 2020). The result shows that the total area of raw paddy fields in 2019 reached 7,463,978 hectares.\n\nBased on the data presented, the figure shows a drastic decrease compared to 2013, amounting to an area of 7,750,990 hectares (AgroIndonesia, 2019). This decline is in line with the opinion of the Director of the Institute for Demographic and Poverty Studies (IDEAS), where the amount of paddy fields decreased in 2023 (Institute for Demographic and Poverty Studies (IDEAS), 2024). An important contributing factor is the environmental conditions, land conversion from agriculture to non-agriculture, printing of paddy fields, and technical aspects of paddy fields basic data collection. (Minister Of Agrarian Affairs And Spatial Planning / Head Of The National Land Agency Menter Decision Agrarian And Spatial Planning/Head Of The National Land Agency Number 686/Sk-Pg.03. 03/XII/2019, 2019).\n\nThe increasing conversion has become a matter of urgency for all sectors to protect paddy fields and address potential environmental damage. Based on these issues, the government has established policies through Law Number 41 of 2009 concerning the Protection of Sustainable Food Agricultural Land and Presidential Regulation Number 59 of 2019 concerning Control of Conversion of Paddy Fields. This reflects the seriousness of addressing protected paddy fields management (Presiden RI, 2019a) but other issues arise from regulations or policies for spatial use. The focus can be directed towards two problems, namely efforts and challenges in implementing policies to control land use conversion, as well as the effects of reformulating policies on achieving national food security. The urgency arises from the potential partiality in the management and protection as well as the lack of consistency between policies in other sectors. Therefore, there is a need for a concept of reformulating policies in spatial use control of land conversion.\n\n\nMethods\n\nThis research method used normative law, conducted by examining existing literature. Furthermore, it is through the conformity of prevailing legal theories using an analytical descriptive method. Through a comprehensive perspective, issues determine the structure of problems within national legal system, such as environmental law and spatial planning (Priyanta & Zulkarnain, 2023). The analysis is implemented by synchronizing primary and secondary legal data (Kholik et al., 2022). To achieve depth and examination of legal data, logical thinking based on philosophy, norms, and jurisprudence can be used (Benuf & Azhar, 2020). The process of legal issue analysis should be subjected to a lengthy process and stages (Tan & Disemadi, 2022). Firstly, analyzing and identifying legal cases with discrepancies between legal ideals and reality. Secondly, justifying legal issues conflicting with regulations related to national food security spatial planning. Thirdly, legal harmonization, and fourthly, analyzing the history or philosophy of law in the formation process (Maldonado et al., 2021).\n\n\nAnalysis and discussion\n\nFood security and development are fundamental values mutually influencing the sustainability of humankind (KILIÇ, 2021). The right to access food is a basic human right, as stated in Article 27 of the 1945 Constitution and reflected in the 1996 Rome Declaration. These considerations form the basis for the establishment of Law No. 7 of 1996 concerning Food and was later amended to Law No. 18 of 2012. The existence shows the importance of food in guaranteeing human rights and the government’s responsibility to ensure food and agricultural land stability. Stability can be achieved by protecting agricultural land and the process requires coordination between the central and regional governments (Rohr et al., 2021) in policy-making process for protecting paddy fields. Meanwhile, food issues cannot be separated from the availability of agricultural land (paddy fields) in implementing the principles of sustainable development (Erwahyuningrum et al., 2023).\n\nThe changing climate development paradigm has become a foundation for the increasing conversion of agricultural into non-agricultural land. This affects national rice production and threatens national food security (Arsini & Surata, 2021) as well as impacting the economy (Lianos & Carballa-Smichowski, 2022). The necessity should show the importance of land tenure aspects in preventing land conversion driven by individuals with land tenure rights (Njeri, 2021). Therefore, there is a need for policy formulation to address the potential land conversion to ensure provision for agriculture. This aims to prevent landowners, particularly individuals with tenure rights over protected paddy fields or sustainable agricultural land. Various efforts are made to maintain land use activities consistent with the designation as agricultural areas. Some policies for providing agricultural land are implemented without addressing the cause of low agricultural productivity, which is inequality in land ownership and management structures relying on large-scale and environmentally damaging extractive industries.\n\nAs seen in policy of providing agricultural land through Food Estate program in Gunung Mas Regency, Central Kalimantan, local farmers were not included in the formulation of policy. In this context, spatial planning including the designation of forest areas was not based on sufficient research. Moreover, the method resulted in the opening up of unproductive land, which was formerly productive forest land.\n\nSpatial planning should include communities since the provision of agricultural land does not result in environmental, land, and social conflicts. This is evident in the significant number of lands located in forest areas, leading to conflicts and difficulties in providing labor. The designation of PSN Food Estate project in Pulang Pisau and Kapuas Regencies also underestimated the biophysical conditions of the region, which are vulnerable and highly prone to forest and land fires. The community has rejected cassava farming in Tewai Baru Village since local biophysical conditions, such as peatlands, are unsuitable for cultivation. These challenges and issues are from the lack of genuine community participation in PSN Food Estate. Meanwhile, the benefits, risks, and potential failures of the project have not been communicated to the community. The government has not reported the commitment to protecting tenure rights, which are inseparable from policies on land provision. This requires a comprehensive method, as outlined in the concept of agrarian reform in the form of asset reform.\n\nThe implementation of Food Estate program should provide opportunities to enhance welfare and empowerment. However, the Tewai Baru Village Government and the community were not given roles and participation in PSN and job opportunities. The impact on the community has prevented Food Estate program from managing the area of food provision land.\n\nThe constraints are not only limited to Food Estate program in Gunung Mas Regency, Central Kalimantan but have been observed in previous research locations, such as Karawang. The results show that 41.9% of farmers have not benefited from asset reform. In terms of regulations, asset reform is governed by Government Regulation Number 65 of 2019 concerning Agricultural Land Area Guarantee. Article 1 reports that the Central and Regional Governments are expected to provide Agricultural Land Area Guarantee on land up to two hectares for farmers practicing food crop cultivation. This guarantee is facilitated by providing ease of access to a. State Land designated for agricultural purposes, and b. Agricultural Land derived from the designation of potential abandoned land.\n\nThe central government has made breakthroughs by issuing Law Number 41 of 2009 concerning the Protection of Sustainable Food Agricultural Land and Presidential Regulation Number 59 of 2019 concerning Control of conversion of Paddy Fields (Arsini & Surata, 2021). There is an authority granted to the Minister of Agrarian Affairs and Spatial Planning/Head of national Land Agency to establish or prevent conversion of paddy fields (Petunjuk Teknis Penyelesaian Ketidaksesuaian Lahan Sawah Yang Dilindungi Dengan Rencana Tata Ruang, Kesesuaian Kegiatan Pemanfaatan Ruang, Izin, Konsesi, Dan/Atau Hak Atas Tanah, 2022).\n\nAt policy level, regulations regarding conversion of paddy fields experience several obstacles, including\n\n1. There is no integration of spatial planning (RTR) regarding mapping, verification and updating of data between the central and regional governments.\n\n2. Direction of regional government political policy.\n\n3. Lack of participatory community participation in implementing LSD.\n\n4. The content or substance of detailed spatial planning plans (RDTR) or regional regulations that do not regulate sanctions, accuracy of protected land objects, and supervision.\n\n5. The imbalance between rice fields and population growth. Many institutions possess authority in managing rice fields influencing the harmonization of policies between one another (Saleh et al., 2022).\n\nDifferent regulations have been enacted on sustainable food agricultural land (LP2B) without addressing land conversion. However, this gap could be exploited by other sectors to carry out land conversions, including the procedures for licensing processes. The challenge of amending previous regulations becomes policy issue in implementing LSD regulations to prevent conversion (Ferisa Nurfauziyah, 2022). The challenge of policy implementation is based on changes leading to alterations within a juridical or formal framework. According to Jenkins, a good method is understanding the effects of the implementation theory on change (Jenkins & Walker, 2022). This concept and foundation of implementation are from political perspectives, including the conduction of affairs by organizations outside and within the political system.\n\nThe implementation also affects the effectiveness of Presidential Regulation Number 59 of 2019 concerning policy on Controlling conversion of Paddy Fields. In this context, protected paddy fields are identified based on satellite images, land verification, and synchronization of verification results. However, discrepancies exist between the satellite images and the synchronization of the protected data. This issue suggests that the government has not fully accommodated the LSD process (Ferisa Nurfauziyah, 2022).\n\nThe increasing population growth indirectly amplifies human personal needs (Hasan, 2021). This analogy propels humans to continually exploit natural resources, unconsciously oriented towards excessive use. There is a need for government-established policies to serve as controls or references for paddy fields management. In this context, policies relevant to the issue are related to spatial planning and land conversion. Another significance is to control the rapid conversion of paddy fields in a region to maintain environmental balance (Linda Cristi Corolina, Choirul Saleh, 2014). The phenomenon requires special attention when productive fields are transformed into industrial or other uses (Angraini et al., 2020). There is a reference for using space and territories through government policies outlined in Law Number 26 of 2007 concerning spatial planning. The aim is to realize a safe, comfortable, productive, and sustainable national territory based on archipelagic insight and resilience. The implementation can be manifested through other related regulations in the planning of paddy fields conversion. The paradigm shift from centralization in spatial planning also changes the system and policy patterns at various levels.\n\nThis is observed in regulations regarding land conversion concerning the registration or verification of paddy fields mapping protected under Minister of ATR/KBPN Regulation Number 12 of 2020 regarding Procedures for Implementing Verification of Paddy Fields Data against Land and Spatial Data, Determination of Protected Paddy Fields Maps, and Recommendation for Land Use Change on Protected Paddy Fields. This policy impacts fields outside the data but has the potential to be designated as protected paddy fields, requiring approval and recommendations. Approval and recommendations are important even though local governments can protect potentially sustainable paddy fields through the establishment of LP2B in regional spatial planning. However, there are substantive differences in land planning methods for food between LP2B and LSD. This is because the definitions and scope of regulation differ, with LSD and LP2B protecting land functions for paddy fields and food commodities, respectively. Spatial planning methods through LSD designation eliminate land provision for food commodities other than paddy fields. The NSPK does not address the need for bottom-up mechanisms, as well as the assessment of land carrying capacity regarding the allocation of space.\n\nBased on the results, various efforts and strategies can overcome the implementation of spatial planning policies for conversion of LSD through:\n\na. Strengthening mechanisms for community participation through spatial planning forums controlled by the Regulation of the Minister of Agrarian Affairs and Spatial Planning/Head of national Land Agency of the Republic of Indonesia Number 9 of 2022 concerning Amendments to the Regulation of the Minister of Agrarian Affairs and Spatial Planning/Head of national Land Agency Number 15 of 2021 concerning Implementation Coordination Spatial planning.\n\nb. Harmonization of the Conformity of Space Use Activities (KKPR) is the compatibility between space use plans and RTR between the center and the regency.\n\nc. Stages of monitoring and evaluating the suitability of spatial planning for conversion of LSD through verification, mapping and data collection (Kompas TV, 2023).\n\nThe three components are inseparable from the technical guidelines for resolving discrepancies between protected paddy fields and spatial plans, the suitability of use activities, permits, concessions, and land rights (Petunjuk Teknis Penyelesaian Ketidaksesuaian Lahan Sawah Yang Dilindungi Dengan Rencana Tata Ruang, Kesesuaian Kegiatan Pemanfaatan Ruang, Izin, Konsesi, Dan/Atau Hak Atas Tanah, 2022). These provisions are reinforced by directives from the Directorate General of Spatial Planning in interview sessions requiring integration as well as monitoring and evaluation stages.\n\nThe issue of food security is a highly sensitive case experienced by almost every country. These include the reduction of land available for production, with other issues arising from the understanding of quantity and location of rice fields (Clauss et al., 2016). In several countries, including China, Vietnam, Malaysia, Thailand, the Philippines, and Indonesia, food security issues are prioritized in official government discussions (Mudji & Ramadhani, 2020). Indonesia’s government is also facing various challenges regarding food security. The current climate change impacts the quality of paddy fields, and the western, eastern, and southern geographical regions have characteristics in agricultural implementation. Furthermore, food security issues can arise due to infrastructure development converting paddy into non-paddy fields, posing a challenge to maintaining national food security stability (Mulyani et al., 2020). Considering National Food Security Agency, the highest factor driving land conversion is infrastructure development in rural and urban areas. This is supported by data from 2014 to 2019 showing a significant increase in infrastructure budget allocations.\n\nFrom Table 2, infrastructure budgets have fluctuated but have reached the highest level in 2024. This budget is allocated for the expansion of toll road sections, airports, ports, housing, apartment buildings, and several offices, requiring extensive land. Due to the development efforts, the government or developers are expected to designate land for implementing development programs by converting paddy fields or other agricultural land sectors. The increased presence of infrastructure has positive impacts on Indonesia’s development. In the process of infrastructure development, the values and principles of agrarian reform should be balanced, namely democracy, justice, and sustainability principles in terms of functions and benefits (Ida Nurlinda, 2009).\n\n\n\n1) Inventory and Identification/Field Validation of ATR/BPN\n\n2) Interpretation and Verification by BIG Imagery September 14, 2019.\n\n\n\n1) CITRA LAPAN/BIG: CSRST 2013-2015, SPOT-6/7 2015-2017, SPOT-6/7 2016-208.\n\n2) Satellite image analysis data and field verification from the Ministry of Agriculture's Balitbangtan/BBSDL\n\n\n\n1) Inventory and identification/Field Validation of ATR/BPN on November 1, 2019.\n\n2) Interpretation and Verification by BIG image on September 14, 2019\n\n\n\n1) GIS data from the Ministry of Agriculture's Data and Data Center\n\n2) Print the rice fields of the Directorate General of PSP, Ministry of Agriculture\n\n3) Location of sample frame area (KSA) segments, BPS\n\n4) Coordination point for field verification results from the Directorate General of PSP, Ministry of Agriculture, LAPAN and the Provincial Agricultural Service\n\n\n\n1) Interpretation and Verification by BIG Imagery on September 14, 2019\n\nThe principles should be balanced with spatial planning, which determines the structure and pattern of space according to various development activities and spatial use in land use changes (Anita et al., 2022). In this context, national food security is affected, considering the impact of infrastructure development (Mishra et al., 2023). There should also be a complementary prevention effort from the central government and local regional authorities. A series of policies are also reported in fulfilling the commitment to prevent and safeguard against conversion of rice into non-rice fields, and these include\n\n1. Law Number 41 of 2009 concerning the Protection of Sustainable Food Land,\n\n2. Government Regulation Number 1 of 2011 concerning the Determination and Conversion of Sustainable Food Agricultural Land,\n\n3. Presidential Regulation Number 59 of 2019 concerning Control of conversion of Rice Fields,\n\n4. Regulation of the Minister of Agrarian Affairs and Spatial Planning/Head of national Land Agency Number 27 of 2019 concerning Land Technical Considerations.\n\nIn Article 44 Paragraph 1 of policy on the protection of sustainable agricultural land in 2009, the Indonesian government has stipulated opposition to conversion of paddy fields designated as sustainable agricultural land. However, in Paragraph 2, there is a provision that land use change may be allowed for public interest reasons, provided the reasons are accompanied by certain requirements and approvals. The granting of permits for conversion requires specific considerations through the establishment of a Technical Review Team for Land Use Change Permits (IPPT), with the task and function of reviewing the land or paddy fields.\n\nBased on research results sourced from the reports of the One-Stop Integrated Investment and Manpower Service Office (DPMPTSP & NAKER), the requests can be formalized through a document containing a description of the land or paddy field. These requirements should meet certain criteria, including Land or paddy fields a) should be consistent with Regional Spatial Planning, b) must not be included in areas prone to natural disasters, c) requiring a permit must not be in water catchment or conservation areas. However, rejection and the refusal to issue a Building Construction Permit (IMB) occur when the requirements are not met. These tiered and rigid requirements reflect the firm stance of the Indonesian government to prevent paddy fields conversion into non-agricultural land (Anggrainy & Isharyanto, 2022). The commitment of the Indonesian government to prevent conversion is also evident from the inclusion of overlapping spatial and agrarian arrangement issues in the important agenda of the vision and mission of national long-term development plan for 2025-2045 (BAPPENAS, 2023).\n\nFood is a fundamental human necessity (Wang et al., 2023) and ensuring the availability is crucial. Harmonious collaboration is required among different sectors to support the availability of high-quality food, including stakeholders from the community, and integrated rice field management policies between the central and regional governments (Radu et al., 2023). Due to the importance of security, the government has prioritized national development agenda for 2022-2024 to enhance the availability, access, and quality of food consumption. The fiscal policies adopted through the 2022 State Budget with the theme of Accelerating Economic Recovery and Structural Reform also include food security as a priority development agenda to promote economic growth (Limanseto, 2021).\n\nThe realization of food security is a vital object in sustaining life for a country. Therefore, there is a need for policy regulations governing national food security, through a sociological method to regulate and improve the quality and safety of food through protected paddy fields (Herjito & Setiawan, 2021). In this context, there are many paddy fields converted into residential or non-agricultural land (Suryadi et al., 2023).\n\nThe government establishes policies for the sustainable protection of agricultural land before the enactment of policies to protect paddy fields. This policy is expected to prevent conversion of agricultural paddy fields into non-agricultural areas. The key point is to focus on strengthening incentives, but policy is land-based. However, this has implications for the incentives given to agricultural landowners who do not convert agricultural land (Sihombing et al., 2021). In this context, the government continues to implement a series of policy breakthroughs regarding land use conversion, which includes forms of activities or initiatives to protect paddy fields (Prasada & Priyanto, 2020).\n\nThe establishment of policies and controls on conversion of protected paddy fields represents the refinement of limitations in previous policies considered inadequate in addressing the issue of conversion. However, the implementation poses challenges in handling land conversion with the introduction of policies to control conversion of paddy fields. The challenges were from an interpretation of a provision suggesting that the presence of an irrigation system might lead to the classification of protected paddy fields (Firmansyah et al., 2021).\n\nThere should be a mechanism regulated in the previous article for mapping since paddy fields under the protection criteria are not automatically designated. This lack of consistency in the strategy and pattern persists, considering many fields are not subject to the mapping process for protection. The lengthy mechanism process slows down the strategy of recording paddy fields after meeting the criteria for protection (Rostini, 2023). The issue impacts spatial planning since consistent implementation is not in line with zoning plans. This is triggered because paddy fields may be part of private property or a strategic project owned by regional governments. In the designation of protected paddy fields, only an aspect of land existence is considered, without compatibility with local neighborhood plans (Diah NikenSari, 2023).\n\nBased on the research, there is a need for reformulation concept regarding policy of spatial planning for protected paddy fields through harmonization. Since the review process designated by the Ministry of ATR/BPN is not an easy task, an integrated mechanism should be initiated in determining paddy fields. Reformulation is a change or improvement to a system, authority, or regulations previously established by the government (Ma & Liu, 2022). This policy is essential when there is an addition or errors in policy determination. Reformulation of food security policies is based on national interests, and the multitude of institutions creates partiality in the implementation of land use conversion prevention policies.\n\nPolicy foundation in preventing land use conversion has been established through Presidential Regulation Number 59 of 2019 concerning the Control of Conversion of Paddy Fields. Concerning the initial basis for the formation, the area or the rate of conversion increases every year. This affects national rice production and threatens food security. Controlling conversion is a strategy to increase domestic production capacity and the control is a priority for national strategic programs (Presiden RI, 2019b). However, the implementation is not accompanied by coordination lines between different institutions. The multitude of institutions and previous policies governing agrarian, spatial planning, and land affairs have not achieved harmony between sectors. Each institution has different directions regarding the planning and use of paddy fields. Conversion for public interest is allowed in the framework regulating the protection of sustainable agricultural land. Moreover, the policy does not define the boundaries and classification designated as non-paddy fields. These provisions are used within society for personal interests under public interest. The presidential regulation on controlling conversion states that at least 5 (five) ministers have the authority to verify, plan, and ensure the efficiency of protected paddy fields. However, policy does not explain the follow-up actions and classification limits on institutional authority through other ministerial regulations. In this context, the ministries have respective authorities and produce different decisions, leading to partiality between sectors.\n\nBased on the analysis and results, there is a need for harmonization concerning policies not addressing the stability of policies regarding protected paddy fields (Nhamo et al., 2020). The lack of defined boundaries of authority between ministerial institutions necessitates reformulation of policies regarding protected paddy fields by adding sub-components of systems, authority, and regulations. The cross-sectoral policy reformulation is achieved by adding clauses to regulate three main interconnected points. These components should be represented in the implementation of LSD conversion prevention and reformulation is as follows:\n\na. Integration Of Policies Between Institutions Or Between Sectors\n\nb. Conformity Of Planning Policies\n\nc. Efficiency Of Rice Land Use Policy\n\nSource: Formulated by the author based on ALG research results, 2023-2024.\n\nThe concept of reformulating policies regarding protected paddy fields is from existing issues. The multitude of institutions with overlapping authorities leads to policy discrepancies in spatial planning and efficient use of paddy fields among different sectors. The absence of defined boundaries of authority results in partial and overlapping data among sectors. This shows the need for reformulation through harmonization (Turimubumwe et al., 2023), and the inclusion of subsystems for integration, compatibility, and efficiency in controlling protected paddy fields. Clear mechanisms and status are essential for use and protection to support national food security. Moreover, cross-sectoral integration or harmonization is required to prevent inconsistencies in authority among ministries, private entities, central government, and local governments.\n\nThe addition of the components reinforces the protection of protected paddy fields, specifically in the integration of policies for spatial planning. Meanwhile, the function of integrated spatial planning can aid in formulating a management system (Lyu et al., 2022). By considering the sub-components of consistency between sectors, policy of controlling conversion strengthens the realization of stability and national food security. Reformulation of existing policies ensures the balanced use of paddy fields, considering the importance of maintaining the balance of rice cultivation and ensuring the stability of national food security in line with the target for 2050 (Ambarwulan et al., 2023). Furthermore, paddy fields are essential for national food security as well as environmental sustainability and economic stability (Toral & Figuerola, 2010).\n\n\nConclusion\n\nIn conclusion, the hierarchical and complementary spatial planning scheme was reported to provide a fundamental basis for the establishment of policy patterns derived from technical aspects. The content of spatial planning served as the basis for land use and control activities, including various policy directions. The graph depicting the increase in paddy fields subjected to conversion showed a potential improvement in rice production and national food security. In this context, the government established policies to control conversion, with the philosophical foundation protecting, fulfilling, and maintaining the availability of paddy fields to support national food needs. At the implementation level, there was a lack of synchronization in formulating policies for paddy fields space with cross-sectoral agrarian reform principles. Examples included the inconsistency and overlapping authorities within the boundaries and policy determination. Therefore, some of policies for protecting paddy fields required reformulation. The concept was based on the integration of policies between institutions or sectors, the consistency of planning policies, and the efficiency of paddy fields use. The implementation should be carried out effectively, efficiently, and optimally through proper governance. This was crucial to support the implementation of national development and food security initiatives.",
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}
|
[
{
"id": "320487",
"date": "08 Oct 2024",
"name": "Siti Rahyla Rahmat",
"expertise": [
"Reviewer Expertise Environmental Economics",
"Development Economics",
"Science Policy",
"Sustainable Development",
"Agricultural Economics."
],
"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 Editor,\nThis manuscript “Reformulation of Policies to Prevent Land Conversion of Rice Fields in Achieving Indonesia’s National Food Security” has quite interesting Problem statement. However the way authors link to the objective and the methodology use is quite simple.\nThe methodology need to be detail. If it is just a desktop review/ document review then it has to be explained clearly on how the articles and document were selected.\nThis study may refer to other countries policy. In its neighbour such as Malaysia, it is not allow to convert paddy field into other land development. It will be more interesting if this research include in-depth interview with some stakeholders in Indonesia.\nSome part in this manuscript can be summarize into figure and table. The way it is written seems a bit dry. Authors are encourage to include some figures/tables in the write up.\nIf this study can be replicated, “Reformulation of Policies” need to be precisely well defined and explain in details. Authors need to justify how this study can be replicated to other industry/countries for food security.\nOverall, this topic is interesting however, the way authors discuss its findings and suggestion need to be improvised.\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? 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? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-945
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https://f1000research.com/articles/12-949/v1
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07 Aug 23
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{
"type": "Research Article",
"title": "Indocyanine green based antimicrobial photodynamic therapy as an adjunct to non-surgical periodontal treatment in periodontal maintenance patients: a clinico-microbiological study",
"authors": [
"Urbashi Roy Chowdhury",
"Deepa Kamath",
"Pooja Rao",
"Suchitra Shenoy M",
"Ramya Shenoy",
"Urbashi Roy Chowdhury",
"Pooja Rao",
"Suchitra Shenoy M",
"Ramya Shenoy"
],
"abstract": "Background: Antimicrobial Photodynamic therapy for the treatment of periodontitis is being increasingly gaining attention but at present, very limited data are available on the clinical and microbiological outcomes obtained following Indocyanine Green as the photosensitizer in Maintenance patients. The objective was to evaluate the efficiency of Indocyanine(ICG)-green based photodynamic therapy as an adjunct to scaling and root planing in patients enrolled in maintenance therapy. Methodology: Using a split mouth study design, 24 participants enrolled in the maintenance therapy, having diagnosed as Periodontitis, were randomly subjected to scaling and root planing(SRP). The test group additionally received ICG-based (Aurogreen®, Aurolabs, Madurai, India,1mg/ml) aPDT with an 810nm diode laser. Clinical assessment of Plaque index, modified Sulcus bleeding index, Probing pocket depth, Clinical loss of attachment and microbiological analysis of A. actinomycetemcomitans, P. gingivalis, T. forsythia and F.nucleatum were performed at baseline and 3 months after treatment. Results: It was observed that although there was no significant difference between the test and control group at baseline and 3 months, there was a statistically significant reduction in the mean values in both the groups at 3 months. Microbiological analysis showed substantial reduction in detection frequency of the bacteria assessed at 3 months in both the groups. Conclusion: Within the limits of the study, ICG-based aPDT did not show additional advantage over SRP alone at 3 months, though it could be a promising treatment modality in maintenance patients in terms of patient comfort and the treatment time taken. More randomised clinical trials should be employed to understand the exact mode of action of ICG based aPDT and its role in treatment of periodontal disease.",
"keywords": [
"Periodontal disease",
"Chronic periodontitis",
"Residual periodontal pockets",
"Photodynamic therapy",
"Laser Therapy",
"Indocyanine Green",
"Maintenance therapy",
"Photosensitizers."
],
"content": "Introduction\n\nPeriodontitis is a result of an exaggerated reaction of the host tissue in response to the microbial challenge which ultimately leads to loss of hard and soft tissues of the periodontium.1 With this sort of a continuous microbial challenge, the periodontal tissues are subjected to toxic bacterial (virulence) factors that have the potential to alter various host cell operations. Periodontal therapy is primarily aimed at removal of these hard tissue and soft tissue deposits from the root surface to prevent progression of the disease. This is achieved by means of scaling and root planing (SRP) by hand and/or power driven instruments.2 However, in spite of being the standard of care for treatment of periodontal disease, SRP may not be sufficient to completely remove all periodontal pathogens.3 The varied clinical presentations such as deep pockets, presence of furcations or intrabony defects may render mechanical debridement inadequate for disruption of the tenacious biofilm which is the primary niche of putative periodontal pathogens.\n\nLASER technology have been around for quite some time now and is currently in the 4th decade in the dental field. It holds a promising non-invasive mode of treatment when it comes to periodontal therapy.4 As discussed previously, periodontal disease causing bacteria not only accumulates on the hard tissue but also can invade the soft tissues of the periodontium. In this regard, Diode lasers have proven to be a boon because they are nothing but soft tissue lasers which have an affinity for pigment containing cells for example black pigmented bacteria (spirochetes).5 LASER also exerts an antibacterial effect which may be further improved by the addition of a photosensitizing dye. This phenomenon is known as photodynamic therapy (PDT).6 Indocyanine green is one such photosensitizer which absorbs wavelength at a range of 750-950 nm with a maximum value of 810 nm and exerts its main action by photo-thermal effect which induces cell damage by increasing intracellular temperature.7 PDT includes a photochemical reaction mediated by oxygen which gets activated on application of light in the presence of a photosensitizing compound that leads to generation of highly reactive nascent oxygen species that are toxic to the microorganisms. The Major advantages of antimicrobial PDT (aPDT) are that they explicitly target cells, causing no collateral damage to non-pigmented host tissue cells and is only initiated when laser light is irradiated. It also lacks the development of resistant bacterial species, which is common with injudicious use of antibiotics.6\n\nResidual pockets may contain periodontal pathogens persistently and may even re-harbour these microorganisms which are incompatible with periodontal health.8 Therefore, such sites need special professional attention. Re-instrumentation repeatedly in these sites may cumulatively cause damage to the hard tissues, thereby calling for maintenance protocols for residual pockets which are efficient even after repeated application.9\n\nRecent body of evidence have shown that adjunctive use of PDT with SRP for treatment of residual periodontal pocket may provide additional improvement and better outcomes. However, there is no available literature which have evaluated the efficacy of the treatment protocol using indocyanine green as a photosensitizer in photodynamic therapy in maintenance patients. Therefore, the purpose of this study is to assess the changes in clinical and microbiological parameters following multiple applications of PDT using indocyanine green and diode laser along with SRP in treating patients enrolled in periodontal maintenance programme.\n\n\nMethods\n\nThe present split-mouth, double-blinded, randomized controlled clinical trial comprised of 25 patients suiting the inclusion criteria. They were recruited from Department of Periodontology, Manipal College of Dental Sciences, Mangalore, India from December 2021 to January 2023.\n\nThe study protocol was reviewed and approved by Institutional Research Ethics Committee and was conducted in accordance with Helsinki Declaration 1975, as revised in 2013(registered at Clinical Trial Registry India as CTRI/2023/01/61447).\n\nInformed consent was taken from all participants intimating them the nature, potential risks, and benefits of their participation in the study. They were free to withdraw from the study at their will. The information sheet and consent form can be found as Extended data.\n\nReference of the present study was taken from Grzech lesniak et al.10 An effect size of 0.2 was considered with a 95% confidence interval and 80% power. Thus, a sample size of 25 was calculated for this split mouth design.\n\n\n\na) Aged above 18 years\n\nb) Chronic periodontitis with residual pockets of ≥4 mm in two different quadrants of the mouth, after completion of active periodontal treatment and currently under maintenance\n\nc) FMPS≤25% (Full-mouth plaque score)\n\nd) FMBS≤25% (Full-mouth bleeding score)\n\n\n\na) Systemic illness that would compromise periodontal status\n\nb) patient on immune-depressant, anti-epileptic, calcium antagonist, blood thinners.\n\nc) Smokers (5 cigarette or more per day)\n\nd) Use of systemic antibiotics in the last twelve months\n\ne) Pregnancy\n\nThe subjects were arbitrarily allocated to either of the interventions: A) (SRP) with antimicrobial photodynamic therapy (aPDT) on right side; SRP on left side or B) SRP right side and aPDT on left side. Selected sites were randomly assigned to one of the two treatment modalities by a computer generated block randomization (allocation ratio of 1:1) before each intervention procedure. A third staff member (RS) who wasn’t directly involved in the study carried out the randomization. Opaque sealed envelopes were used to conceal the allocation sequence. The primary investigator, outcome assessor, biostatistician as well as the patients were unaware of the details of the series of the study. As and when a patient came and fit the criteria for the study, the envelope was opened and treatment protocol was followed as described below.\n\nTreatment protocol\n\nPeriodontal measurements\n\nAll 25 Patients underwent full mouth clinical periodontal assessment around all teeth by a single calibrated examiner (DK) following the CONSORT guidelines (Figure 1: consort flow chart).11 The measurements were taken at four sites per tooth (distal, mesial, facial/buccal, lingual/palatal) using a University of North Carolina No.15 periodontal probe (Hu-friedy™, Chicago IL) and Customized acrylic stents were prepared to guide the probe placement in the same plane. Clinical variables included the measurements of plaque index (PI), modified sulcular bleeding index (mSBI), probing pocket depth (PD) and clinical attachment level (CAL). PD was measured as the distance between the gingival margin and the base of the pocket and CAL was calculated as the distance from the CEJ and the bottom of the sulcus or of the periodontal pocket. The primary outcome being probing depth and clinical attachment level based on the number of sites and secondary outcome being plaque index and bleeding index.\n\nPreparation of indocyanine green\n\nUnder aseptic circumstances a fresh 5 mg/mL solution with the photosensitizer dye Indocyanine green (Aurogreen®, Aurolabs, Madurai, India) was prepared. In 5ml of sterile water, ICG is dissolved to prepare an initial 5 mg/mL ICG stock solution. This solution is further diluted in saline solution at the ratio of 1:5 to achieve the final ICG concentration of 5 mg/mL.12 The aqueous solution becomes unstable on coming in contact with the environment and hence should be utilised on the same day within 10 hours.\n\nLaser parameters\n\nThe laser system used in the study is Diode laser (Picasso AMD) with wavelength of 810 nm. It was applied in a continuous mode, circumferentially around the tooth, with a power of 2 W for 60 s. Total energy produced is 6 J/cm2.\n\nMicrobiological assessment\n\nMicrobiological samples were collected through plaque from the deepest periodontal pockets at baseline and three months after therapy using sterile curettes (Figure 2). They were then transferred to Eppendorf tubes containing 500 μL of sterile phosphate buffer saline (PBS). Microbiological analysis consisted of a molecular test for the detection of four periodontal pathogens. The test was performed with Multiplex PCR (polymerase chain reaction) method. Bacterial DNA was extracted using DNA thermal cycler (ProFlex™ 3× 32-well PCR System, Applied Biosystems, Foster City, CA) following the instructions of the manufacturer (Table 1).\n\nThe following periodontal pathogenic species were analysed:\n\n• Aggregatibacter actinomycetemcomitans\n\n• Porphyromonas gingivalis\n\n• Fusobacterium nucleatum\n\n• Tannerella forsythia\n\nImmediately after full mouth SRP, the photosensitizer (0.5 mL) was applied in the test site using a syringe. To avoid ‘carry-across’ effect, a conscious effort was made to not spill the photosensitizer in other parts of the oral cavity. Anyhow, the dye is not known to get activated without laser light. Distilled water was used after 2 minutes to wash out the free photosensitizer. The diode soft tissue laser was brought in contact with the gingival tissues below the gingival margin and light was applied for 60 seconds in a circumferential manner around the tooth. The laser fibre tip was kept in contact with the soft tissue wall constantly (Figure 3). The strokes addressed small sections and were systematically overlapping. The fibre tip was continually inspected to remove any accumulated debris with water moistened gauze. aPDT was repeated after 14 days.\n\nThe contralateral site received sham LASER which imitated the irradiation without it being turned on. All the patients were monitored for 3 months.\n\nStatistical analysis was done for all the clinical parameters and microbiological parameters. Mean and standard deviation was calculated at baseline and at 3 months’ follow-up. Data was analysed using paired ‘t’ test for plaque index, gingival index, clinical attachment level and probing depth at baseline and at 3 months’ follow-up. Mc Nemar P test and Fischer exact P test were used for microbiological parameters. Statistical Package for Social Sciences (SPSS), version 17 (SPSS Inc, Chicago IL) was the used software. A P value of <0.05 was considered significant.\n\n\nResults\n\nThis split mouth, single centre, randomised controlled trial was done for a period of 3 months. There were no unwanted events reported by any patient throughout the study. Out of 25 subjects initially recruited, one was lost to drop out and subsequently 24 patients were carried forward for analysis. 10 participants were females and 14 were males, aged between 30 and 78 years. The age and sex distribution of both groups were uniform (P>0.05) (Table 2). A total of 130 teeth were examined, 66 in test group and 64 in control group, with 171 intervention sites: 86 in test group and 85 in control group.\n\nThe participants in the study showed decreased full mouth plaque score (FMPS) and full mouth bleeding score (FMBS) that is <25%. This signifies that all of them had maintained an optimum standard of oral hygiene throughout the study period. The results also showed a substantial reduction of PI, mSBI throughout the study period in both groups with P value of <0.000 (Table 3).\n\n* Statistically significant at P<0.05.\n\n† Not statistically significant at P>0.05.\n\nThere was statistical significance from baseline to 3 months regarding PD with values of 1.73±0.42 mm and 1.22±0.43 mm respectively for the test group and 1.70±0.46 mm and 1.28±0.42 mm respectively for the control group (P value <0.05). Similarly, for gain in CAL in the test group, there was a statistically significant difference from baseline (1.77±0.40 mm) to 3 months (1.27±0.41mm) and in the control group from baseline (1.73±0.46 mm) to 3 months (1.30±0.41 mm) (P value <0.05). However, intergroup comparison of PD and CAL did not show any statistical significance at any given period (P>0.05) (Table 3).\n\nAll groups exhibited a substantial decrease in the detection frequency of A.a, P.g, T.f, F.n from baseline till the termination of the study (Figure 4: test) and (Figure 5: control). Both the groups showed equally greater reduction in detection frequency of P.g and T.f at 3 months.\n\n\nDiscussion\n\nThe corner-stone of cause-related therapy is considered to be non-surgical periodontal therapy (NSPT) which encompasses the removal of supragingival and subgingival biofilm and calculus.13 Yet, a number of ‘residual pockets’ often remain after non-surgical periodontal therapy.14 Residual pockets, particularly >4 mm, have shown to be a positive predictor of clinical loss of attachment over the years and hence represents a clinical scenario which is more difficult to treat than a patient of untreated periodontitis15.16 Photodynamic therapy has been used in periodontal treatment for over a quarter of a century now. They are being increasingly used as adjunctive treatment with NSPT and eliminates disadvantage such as bacterial resistance seen with systemic or local antibiotics.17\n\nThis study focussed on evaluating the clinical and microbiological effects of antimicrobial photodynamic therapy using indocyanine green in patients enrolled in maintenance therapy, having residual pockets. The use of a split mouth design in the present study provided an advantage over parallel design study where the same subject served as control, hence comparison of all treatment methods could be done under similar and optimally standard healing periods. A statistically significant improvement was seen at 3 months for plaque scores and bleeding scores in both the intervention groups without any intergroup differences at any given point. There was a significant reduction in the probing pocket depth and considerable gain in clinical attachment level at the end of 3 months in both groups (Figure 6). However, the difference between the two groups were not statistically significant. There are studies which are in agreement with the present study6,18.19 A systematic review by Azarpazhooh et al. (2010) demonstrated that PDT as a treatment modality whether stand-alone or as adjunct, was not superior to SRP therapy alone.20\n\nHowever, a systematic review of four RCTs by Xue et al(2017) stated that additional clinical improvement were observed in SRP+PDT group compared to SRP alone for residual pockets for supportive periodontal therapy.21 As none of the studies used Indocyanine green as the photosensitizer, no clear-cut conclusion can be drawn. With that, coming to the next aspect- the photosensitizer, majority of available literature on PDT demonstrate the use of conventional photosensitizers that are methylene blue or toluidine blue. The present randomised controlled trial is the first to determine the outcome of PDT using Indocyanine Green as the photosensitizing agent in treatment of residual pockets in maintenance therapy patients. However, the outcomes in the current study, though favourable at 3 months, did not prove added benefits of ICG compared to SRP alone. This is not commensurate with previous studies utilising ICG as photosensitizing agent. A systematic review conducted by Bashir et al (2021) concluded that ICG mediated PDT in treatment of periodontitis significantly improved the clinical outcomes compared to SRP alone.22 This disparity may be due to the fact that there is no standardised protocol for use of soft tissue diode LASER and the frequency of antimicrobial PDT application for treatment of periodontal disease. Lack of standardisation eliminates many studies for analysis in systematic reviews. Also, the utilisation of ICG in the field of periodontitis is relatively new hence it should be acknowledged that there may have been studies which are yet in the process of trial, or have gone through publication.\n\nRegarding microbiological analysis, the detection frequencies of the 4 major putative periodontal pathogens were analysed. The detection frequencies of P.g, A.a, T.f, F.n were significantly lower at 3 months (Figure 7). Even though the detection frequency lowered at the end of the study for all the pathogens, there was no statistical significance in any of the groups from baseline to 3 months. This may be due to the fact that the sample size for the present study was limited and for analysis of non-parametric variable such as the absence or presence of micro-organisms, a bigger sample size is necessary to demonstrate the effectiveness of the treatment modality.\n\nNo intergroup association was observed with respect to the presence of bacteria. Similar results were reported by Chondros et al. (2009),18 Polansky et al. (2009),23 De Micheli et al. (2011)24 and Giannopoulou et al. (2012).25 Polansky and group tested for P. gingivalis, T. forsythia and T. denticola at baseline and at 3 months. The levels of prevotella species (P.g) had significantly come down in both the groups. No significant reductions of T. forsythia and T. denticola were observed in either groups. Moreover, DeMicheli and group (2011) did not observe any additional reduction in the bacterial species in the test group (diode laser with SRP). Similar to the present study where the detection frequency of each organism tested, reduced significantly at 3 months, a systematic review of 17 randomised controlled clinical trials, by Akram et al. (2016)26concluded that adjunctive PDT application led to a reduction of the following species A.a, P.g, T. f, and T.d equal to the control group (SRP alone). This was in line with another study by Cappuyns et al. (2011)19 who demonstrated that detection frequency of P.g, T.f and T.d significantly reduced 2 and 6 months following intervention in all the groups that is SRP, DSL and PDT and that one procedure was not superior to the other.\n\nThe present study employed two sittings of PDT application similar to an earlier study by Segarra (2017) that have shown at least two applications of PDT is necessary to achieve the expected outcome.27 On the contrary a study by Müller Campanile et al. (2015) demonstrated that the number of applications is not proportional to better outcomes of PDT.28 Although there are not many systematic reviews to authenticate the statement, most of the available literature regarding the number of sittings of PDT emphasize of multiple sittings of atleast 2 or more than 2 to attain the desired effect29.30 Maybe future trials can implement more than 2 sittings for treating residual pockets.\n\nIt is noteworthy to consider other limitations of the present study. Firstly, a bigger sample size is necessary to validate the use of indocyanine based PDT in maintenance patients. The time period taken as 3 months for the duration of the study provided a short term overview about the effect of different treatment modalities. A longer study period can be implied in future studies. There could be chances that the periodontopathogens could translocate from one niche to another within the oral cavity- which is known as intraoral translocation. This may explain the variable results obtained within the same patients from different treatment modalities.\n\n\nConclusion\n\nTo date, successful application of antimicrobial photodynamic therapy remains conflicting and insufficient. This is because of the variation in methodology, poorly defined treatment parameters and the lack of a standard protocol in form of dosimetry or appropriate illumination devices. The present study does not show additional benefits of PDT over SRP; however, it does not negate the role of PDT with indocyanine green. Improvement was seen in the test and control group alike at the termination of the study period, though not statistically significant. Hence, future investigations should aim at standardising the treatment protocols of LASER, utilising indocyanine green in treatment of residual pockets, in a larger population. Furthermore, a quantitative analysis of the micro-organisms should be intended which would give us an enhanced understanding and prove the efficacy of ICG based antimicrobial photodynamic therapy.",
"appendix": "Data availability\n\nFigshare: Underlying data for “Indocyanine green based antimicrobial photodynamic therapy as an adjunct to non-surgical periodontal treatment in periodontal maintenance patients: a clinico-microbiological study”. https://doi.org/10.6084/m9.figshare.23573952. 31\n\nThe project contains the following underlying data:\n\n1. Data file 1: Master chart containing raw data of both test group and control group at baseline and at 3 months (Table containing the raw data of the study)\n\nFigshare: Extended data for “Indocyanine green based antimicrobial photodynamic therapy as an adjunct to non-surgical periodontal treatment in periodontal maintenance patients: a clinico-microbiological study”. https://doi.org/10.6084/m9.figshare.23574150. 32\n\nThe project contains the following underlying data:\n\n1. Case Performa\n\n2. Informed consent form in English\n\n3. Ethical Committee Approval letter\n\nFigshare: CONSORT check list and flow chart for “Indocyanine green based antimicrobial photodynamic therapy as an adjunct to non-surgical periodontal treatment in periodontal maintenance patients: a clinico-microbiological study”, https://doi.org/10.6084/m9.figshare.23574162. 33\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nHaffajee AD, Socransky SS: Microbiology of periodontal diseases: introduction. Periodontol. 2005; 38(1): 9–12. Publisher Full Text\n\nCobb CM: Clinical significance of non-surgical periodontal therapy: an evidence-based perspective of scaling and root planing. J. Clin. Periodontol. 2002; 29: 22–32. Publisher Full Text\n\nSlots J, Rosling BG: Suppression of the periodontopathic microflora in localized juvenile periodontitis by systemic tetracycline. J. Clin. Periodontol. 1983; 10(5): 465–486. Publisher Full Text\n\nCobb CM: Lasers and the treatment of periodontitis: the essence and the noise. Periodontol. 2017; 75(1): 205–295. PubMed Abstract | Publisher Full Text\n\nKonopka K, Goslinski T: Photodynamic Therapy in Dentistry. J. Dent. Res. 2007; 86(8): 694–707. Publisher Full Text\n\nChondros P, Nikolidakis D, Christodoulides N, et al.: Photodynamic therapy as adjunct to non-surgical periodontal treatment in patients on periodontal maintenance: A randomized controlled clinical trial. Lasers Med. Sci. 2009; 24(5): 681–688. PubMed Abstract | Publisher Full Text\n\nHouthoofd S, Vuylsteke M, Mordon S, et al.: Photodynamic therapy for atherosclerosis. The potential of indocyanine green. Photodiagn. Photodyn. Ther. 2020; 29: 101568. PubMed Abstract | Publisher Full Text\n\nMombelli A, Schmid B, Rutar A, et al.: Persistence Patterns of Porphyromonas gingivalis, Prevotella intermedia/nigrescens, and Actinobacillus actinomycetemcomitans After Mechanical Therapy of Periodontal Disease. J. Periodontol. 2000; 71(1): 14–21. PubMed Abstract | Publisher Full Text\n\nLang NP: Group B. Reactor report. Non-surgical periodontal therapy: mechanical debridement, antimicrobial agents and other modalities. J. Int. Acad. Periodontol. 2015; 17(1 Suppl): 31–33. PubMed Abstract\n\nGrzech-Leśniak K, Gaspirc B, Sculean A: Clinical and microbiological effects of multiple applications of antibacterial photodynamic therapy in periodontal maintenance patients. A randomized controlled clinical study. Photodiagnosis Photodyn Ther. 2019; 27: 44–50. PubMed Abstract | Publisher Full Text\n\nPandis N, Chung B, Scherer RW, et al.: CONSORT 2010 statement: extension checklist for reporting within person randomised trials. BMJ. June 30, 2017; 357: j2835. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSethi K, Raut C: Antimicrobial photodynamic therapy using indocyanine green as a photosensitizer in treatment of chronic periodontitis: A clinico-microbial study. Indian J. Dent. Res. 2019. Publisher Full Text\n\nGraziani F, Karapetsa D, Alonso B, et al.: Nonsurgical and surgical treatment of periodontitis: how many options for one disease? Periodontol. 2017; 75(1): 152–188. PubMed Abstract | Publisher Full Text\n\nAdriaens PA, Adriaens LM: Effects of nonsurgical periodontal therapy on hard and soft tissues. Periodontol. 2004; 36(1): 121–145. Publisher Full Text\n\nClaffey N, Nylund K, Kiger R, et al.: Diagnostic predictability of scores of plaque, bleeding, suppuration and probing depth for probing attachment loss. 31/2-years of observation following initial periodontal therapy. J. Clin. Periodontol. 1990; 17(2): 108–114. PubMed Abstract | Publisher Full Text\n\nChapple ILC, Mealey BL, Van Dyke TE, et al.: Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J. Periodontol. 2018; 89: S74–S84. PubMed Abstract | Publisher Full Text\n\nArdila CM, Granada MI, Guzmán IC: Antibiotic resistance of subgingival species in chronic periodontitis patients. J. Periodontal Res. June 10, 2010; 45: 557–563. PubMed Abstract | Publisher Full Text\n\nChondros P, Nikolidakis D, Christodoulides N, et al.: Photodynamic therapy as adjunct to non-surgical periodontal treatment in patients on periodontal maintenance: a randomized controlled clinical trial. Lasers Med. Sci. 2009; 24(5): 681–688. PubMed Abstract | Publisher Full Text\n\nCappuyns I, Cionca N, Wick P, et al.: Treatment of residual pockets with photodynamic therapy, diode laser, or deep scaling. A randomized, split-mouth controlled clinical trial. Lasers Med. Sci. 2012; 27(5): 979–986. PubMed Abstract | Publisher Full Text\n\nAzarpazhooh A, Shah PS, Tenenbaum HC, et al.: The Effect of Photodynamic Therapy for Periodontitis: A Systematic Review and Meta-Analysis. J. Periodontol. 2010; 81(1): 4–14. Publisher Full Text\n\nXue D, Zhao Y: Clinical effectiveness of adjunctive antimicrobial photodynamic therapy for residual pockets during supportive periodontal therapy: A systematic review and meta-analysis. Photodiagn. Photodyn. Ther. 2017; 17: 127–133. PubMed Abstract | Publisher Full Text\n\nBashir NZ, Singh H-A, Virdee SS: Indocyanine green–mediated antimicrobial photodynamic therapy as an adjunct to periodontal therapy: a systematic review and meta-analysis. Clin. Oral Investig. 2021; 25(10): 5699–5710. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPolansky R, Haas M, Heschl A, et al.: Clinical effectiveness of photodynamic therapy in the treatment of periodontitis. J. Clin. Periodontol. 2009; 36(7): 575–580. Publisher Full Text\n\nDe Micheli G, de Andrade AKP , Alves VTE, et al.: Efficacy of high intensity diode laser as an adjunct to non-surgical periodontal treatment: a randomized controlled trial. Lasers Med. Sci. 2011; 26(1): 43–48. PubMed Abstract | Publisher Full Text\n\nGiannopoulou C, Cappuyns I, Cancela J, et al.: Effect of Photodynamic Therapy, Diode Laser, and Deep Scaling on Cytokine and Acute-Phase Protein Levels in Gingival Crevicular Fluid of Residual Periodontal Pockets. J. Periodontol. 2012; 83(8): 1018–1027. PubMed Abstract | Publisher Full Text\n\nAkram Z, Al-Shareef SAA, Daood U, et al.: Bactericidal Efficacy of Photodynamic Therapy Against Periodontal Pathogens in Periodontal Disease: A Systematic Review. Photomed. Laser Surg. 2016; 34(4): 137–149. PubMed Abstract | Publisher Full Text\n\nSegarra-Vidal M, Guerra-Ojeda S, Vallés LS, et al.: Effects of photodynamic therapy in periodontal treatment: A randomized, controlled clinical trial. J. Clin. Periodontol. 2017; 44(9): 915–925. Publisher Full Text\n\nMüller Campanile VS, Giannopoulou C, Campanile G, et al.: Single or repeated antimicrobial photodynamic therapy as adjunct to ultrasonic debridement in residual periodontal pockets: clinical, microbiological, and local biological effects. Lasers Med. Sci. 2015; 30(1): 27–34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMuzaheed AS, Hakami AR, et al.: Effectiveness of single versus multiple sessions of photodynamic therapy as adjunct to scaling and root planing on periodontopathogenic bacteria in patients with periodontitis. Photodiagn. Photodyn. Ther. 2020; 32: 102035. PubMed Abstract | Publisher Full Text\n\nIvanaga CA, Miessi DMJ, Nuernberg MAA, et al.: Antimicrobial photodynamic therapy (aPDT) with curcumin and LED, as an enhancement to scaling and root planing in the treatment of residual pockets in diabetic patients: A randomized and controlled split-mouth clinical trial. Photodiagn. Photodyn. Ther. 2019; 27: 388–395. PubMed Abstract | Publisher Full Text\n\nRoy Chowdhury U, Kamath DG, Rao P, et al.: Master chart containing raw data of both test group and control group at baseline and at 3 months. Dataset. figshare. 2022. Publisher Full Text\n\nRoy Chowdhury U, Kamath DG, Rao P, et al.: Extended data. Dataset. figshare. 2022. Publisher Full Text\n\nRoy Chowdhury U, Kamath DG, Rao P, et al.: Repository data. Dataset. figshare. 2022. Publisher Full Text"
}
|
[
{
"id": "266858",
"date": "01 Jul 2024",
"name": "Swati Setty",
"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\nThis manuscript has adopted a proper study design with the support of current literature. The need for research on photodynamic therapy has been described. The methodology of the study is adequate. The interpretation of the results is appropriate. Discussion includes the related literature of the study. Limitations have been explained correlating with the current evidence. The requirement for further research has been stated clearly.\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": "222649",
"date": "01 Jul 2024",
"name": "Anurag Satpathy",
"expertise": [
"Reviewer Expertise Periodontal Regeneration",
"Periodontal Microbiology",
"Autologus platelet concentrate",
"Periodontal Medicine"
],
"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\nAuthors have carried out the study \"Indocyanine green based antimicrobial photodynamic therapy as an adjunct to non-surgical periodontal treatment in periodontal maintenance patients\"\nWhile PDT is an accepted treatment modality and research continues to unravel the inconsistencies in the evidence, there are several areas in the present study where there is deficiency and lack of clarity.\n1. The timeline of treatment and its interval needs to be clarified. What was the time gap between the SRP and sample collection?\n2. Authors state that the inclusion criteria is greater than 4 mm probing depth. However, the PD in both groups at baseline is less than 3 mm.\n3. The McNemars test results are not presented\n4. Split mouth design with microbial assessment comparison between treatment and control has the chances of relocation of microbes\n5. PDT protocol is unclear.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "12223",
"date": "20 Aug 2024",
"name": "DEEPA KAMATH",
"role": "Author Response",
"response": "1. The timeline of treatment and its interval needs to be clarified. What was the time gap between the SRP and sample collection? Response : Changes done. PDT application was done at baseline and again after 14 days. However, the clinical and microbiological assessment was done at baseline and after 3 months only 2. Authors state that the inclusion criteria is greater than 4 mm probing depth. However, theÃÂ PD in both groups at baseline is less than 3 mm. Response: The results were calculated as follows- Sum of pocket depth of test/control sites of an individual divided by total number of sites of the selected teeth. However, the calculations are re-checked and changes in the values are made. 3.The McNemars test results are not presented Response: Changes done. Table 4 has been added showing the results of Mc Nemar P Test. The same had been depicted graphically in the old version. 4. Split mouth design with microbial assessment comparison between treatment and control has the chances of relocation of microbes Response : This has been mentioned as one of the drawbacks of the study. Besides, there are no statistical tests to detect carry-across effect. However, split mouth designs do provide with better standardisation in terms of reduced variability. 5. PDT protocol is unclear. Response: Changes done. a-PDT was carried out at baseline after completion of full mouth SRP of the selected individuals and repeated after 14 days. The preparation of dye was according to the instructions provided in the product manual."
}
]
}
] | 1
|
https://f1000research.com/articles/12-949
|
https://f1000research.com/articles/12-1594/v1
|
14 Dec 23
|
{
"type": "Case Report",
"title": "Case Report: Tolosa-Hunt syndrome, a neuroinflammatory origin of painful ophthalmoplegia",
"authors": [
"Amro Abdelrahman",
"Moayad Elgassim",
"Asmaa Abdalkarim",
"Anas Mohamed Babiker",
"Muhnad Abdeen",
"Shahd M. Abass",
"Isra Babiker",
"Gufran Algaly",
"Khalid Y. Fadul",
"Sara M.I. Ahmed",
"Fajr Jamal A. Bagi",
"Muhammad Abugabala",
"Amin Saied",
"Mohamed Elgassim",
"Amro Abdelrahman",
"Moayad Elgassim",
"Asmaa Abdalkarim",
"Anas Mohamed Babiker",
"Muhnad Abdeen",
"Shahd M. Abass",
"Isra Babiker",
"Gufran Algaly",
"Khalid Y. Fadul",
"Sara M.I. Ahmed",
"Fajr Jamal A. Bagi",
"Muhammad Abugabala",
"Amin Saied"
],
"abstract": "Background Tolosa-Hunt syndrome is a rare neuroinflammatory disease that affects the cavernous sinus and superior orbital fissure, resulting in symptoms of neuropathy.\n\nCase presentation We report a case of a 35-year-old male patient with no past medical history who presented to the emergency department (ED) complaining of a four-day history of progressively increasing headaches associated with right eye pain and double vision. A physical examination showed findings suggestive of abducens nerve palsy. A computed tomography (CT) scan showed subtle asymmetric thickening of the right cavernous sinus, which prompted further investigation by magnetic resonance imaging (MRI) scan. The MRI scan showed intensely enhanced soft tissue thickening in the right cavernous sinus region, slightly extending to the right orbital apex, which caused enlargement of the cavernous sinus and appeared isointense to the adjacent muscles on T1 and T2. The diagnosis of Tolosa-Hunt syndrome was made after the exclusion of all other possible pathologies. The patient received prednisolone therapy; his symptoms improved, and he was discharged after three days. Two weeks later, the patient presented again to the ED with the same symptoms and was treated symptomatically.\n\nConclusions This case highlights a very rare etiology for painful ophthalmoplegia, which is Tolosa-Hunt syndrome. Thickening of the cavernous sinus on MRI images with a background history of painful ophthalmoplegia and headache should raise clinician’s suspicion towards the disease. In addition, exclusion of other possible causes is very important, as Tolosa-Hunt syndrome is a diagnosis of exclusion.",
"keywords": [
"Tolosa Hunt syndrome",
"Painful ophthalmoplegia",
"Headache",
"Cavernous sinus",
"Neurology",
"Ophthalmology"
],
"content": "Introduction\n\nTolosa-Hunt syndrome is a disease characterized by granulomatous inflammation affecting the cavernous sinus and/or superior orbital fissure. This inflammation leads to the compression of various cranial nerves and subsequent neuropathic symptoms. This condition was originally documented in 1954.1 Tolosa-Hunt syndrome manifests as ptosis, discomfort in the orbital, periorbital, or hemicrania areas, and ophthalmoplegia (partial or full).2 Typically, inflammation originates in the cavernous sinus and then extends towards the superior orbital fissure and orbital cavity. This condition presents as recurring episodic attacks, following a pattern of relapsing and remitting. According to reports, there are about one in a million cases affected by this disease annually.1\n\nHere we describe a 35-year old male patient who presented to the hospital with headache and right eye pain. A magnetic resonance imaging (MRI) scan showed thickening in the cavernous sinus region. He was diagnosed as a case of Tolosa-Hunt syndrome after exclusion of all other potential diagnosis. This case report follows the CARE checklist.8\n\n\nCase presentation\n\nA 35-year-old Egyptian male patient, with no past medical history presented to the emergency department (ED) of Hamad hospital complaining of a four-day history of progressively increasing headaches associated with right eye pain and double vision. According to the patient, the headache mainly affected the right and frontal sides of the head and was associated with nausea and three episodes of non-bloody vomiting. He denied any recent history of head trauma, loss of consciousness, fever, neck stiffness, or photophobia.\n\nIn the ED, his vital signs were within normal limits. Physical examination revealed impaired abduction of the right eye with horizontal nystagmus on lateral gaze consistent with right abducens nerve palsy. Careful examination of both upper and lower extremities was unremarkable. No motor or sensory deficits were noted. Kernig’s and Brudzinski’s signs were negative. Examination of other systems was unremarkable.\n\nThe patient’s lab results, including a complete blood count and comprehensive metabolic panel, were within normal ranges. A computed tomography (CT) scan result showed subtle asymmetric thickening of the right cavernous sinus. However, given the strong clinical suspicion of Tolosa-Hunt syndrome, the radiologist recommended doing magnetic resonance imaging (MRI) scan of the head and orbital region. Following discussion with neurology team, the patient received painkillers and was admitted to the medical floor for further management. The neurology team recommended cerebrospinal fluid analysis (CSF), autoimmune, and vasculitis workups to narrow down the differential diagnoses.\n\nResults of the MRI revealed an intensely enhanced soft tissue thickening in the right cavernous sinus region, slightly extending to the right orbital apex, which caused enlargement of the cavernous sinus and appeared isointense to the adjacent muscles on T1 and T2 (Figure 1).\n\nMagnetic resonance imaging (MRI) showing enhancing soft tissue thickening in the right cavernous sinus region (red arrow). (A): Axial view. (B) Coronal view.\n\nCSF analysis through Lumbar puncture (LP) was done, and while waiting for the results, the patient was started on oral prednisolone 60 mg for three days and then tapered off. The results of the CSF analysis came back negative, and the results of the autoimmune and vasculitis workup also came back negative. A diagnosis of Tolosa-Hunt Syndrome was made, and the patient was discharged on oral prednisolone at 60 mg with a follow-up visit to a neurology clinic after 6 weeks. Two weeks later, the patient presented to the ED again with a headache and right eye pain after his symptoms had initially improved. He was treated symptomatically and discharged on the same day.\n\n\nDiscussion\n\nTolosa-Hunt syndrome stands as an uncommon entity of painful ophthalmoplegia, originating from non-specific inflammation within the cavernous sinus. The National Organization for Rare Disorders (NORD) states that the disease typically emerges around the median age of 41 years, affecting both sexes.3 Our patient, however, was a 35-year-old male, which is relatively young in contrast to the average age of onset.\n\nThe specific etiology of the disease is not fully understood.2 A non-specific granulomatous inflammation of the cavernous sinus with varying extension into the superior orbital fissure and orbital apex, along with infiltration of lymphocytes and plasma cells, is the primary characteristic of the disease. When patients present with symptoms of ophthalmoplegia and headache, it is necessary to rule out other malignant and autoimmune conditions, even though it is typically thought of as a benign condition. Understanding the differential diagnosis is more crucial to exclude other causes than it is to confirm the condition,4 as a requirement for the diagnostic criteria as per The International Classification of Headache Disorders (ICHD).\n\nTolosa Hunt’s Diagnostic criteria as per ICHD’s latest edition in 20185 includes the following:\n\n“A. Unilateral orbital or periorbital headache fulfilling criterion C\n\nB. Both of the following:\n\n1. Granulomatous inflammation of the cavernous sinus, superior orbital fissure or orbit, demonstrated by MRI or biopsy\n\n2. Paresis of one or more of the ipsilateral cranial nerves III, IV and/or VI\n\nC. Evidence of causation demonstrated by both of the following:\n\n1. Headache is ipsilateral to the granulomatous inflammation\n\n2. Headache has preceded paresis of the nerves III, IV and/or VI by 2 weeks, or developed with it\n\nD. Not better accounted for by another ICHD-3 diagnosis”\n\nGenerally, MRI is a cornerstone in diagnosing pathologies of the cavernous sinus. In the case of Tolosa Hunt syndrome, the classical appearance is enhancing soft-tissue thickening of the cavernous sinus and superior orbital fissure that appears isointense to gray matter on T1-weighted images and iso- to hypointense on T2-weighted images.6\n\nOur patient presented with a headache and right eye pain, and the physical examination showed a sixth (IV) cranial nerve palsy (Abducens nerve palsy). The results of the CT scan showed subtle asymmetric thickening of the right cavernous sinus. However, the radiology team recommended an MRI scan, as the clinical history and examination were highly suggestive of Tolosa-Hunt syndrome. The MRI results showed intensely enhanced soft tissue thickening in the right cavernous sinus region, slightly extending to the right orbital apex, which caused enlargement of the cavernous sinus and appears isointense to the adjacent muscles on T1 and T2. In addition, the results of the autoimmune, vasculitis, and CSF workups were all negative.\n\nSince the disorder is inflammatory, high-dose glucocorticoids are the main course of therapy.1 A progressive oral taper over a period of weeks is advised after an initial high-dose steroid therapy. Neuropathies may take months to resolve, requiring a longer steroid regimen. Neurological impairments may occasionally last a lifetime. Persistent MRI abnormalities should not affect the recommended length of therapy unless they show no regression because radiological improvement also takes time to resolve. Overall, 50% of individuals have a recurrence of the illness.7\n\nAfter admission, our patient started prednisolone treatment with an initial dose of 60 mg for three days, followed by a tapering dose. He was discharged with a follow-up with a neurology clinic after 6 weeks. Two weeks later, he presented again to the ED with a headache and right eye pain, although his symptoms had initially improved with treatment. He was treated symptomatically and discharged on the same day.\n\n\nConclusions\n\nTolosa-Hunt syndrome is a very rare neuroinflammatory condition that presents as painful ophthalmoplegia. Thickening of the cavernous sinus on MRI images with a background history of ophthalmoplegia and headache is highly suggestive of Tolosa-Hunt syndrome. However, as the disease is a diagnosis of exclusion, it’s very crucial for clinicians to exclude other possible pathologies of painful ophthalmoplegia before establishing the diagnosis of Tolosa-Hunt syndrome.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and clinical images was obtained from the patient.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nZenodo: CARE checklist for “Case Report: Tolosa-Hunt syndrome, a neuroinflammatory origin of painful ophthalmoplegia”. https://doi.org/10.5281/zenodo.8360931. 8\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nOpen Access funding provided by Qatar National Library.\n\n\nReferences\n\nAmrutkar C, Burton EV: Tolosa-Hunt Syndrome. [Updated 2023 Aug 8]. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Reference Source\n\nPaovic J, Paovic P, Bojkovic I, et al.: Tolosa-Hunt syndrome—diagnostic problem of painful ophthalmoplegia. Vojnosanit. Pregl. 2012; 69: 627–630. PubMed Abstract | Publisher Full Text\n\nTolosa hunt syndrome - symptoms, causes, treatment: Nord.2023 [cited 2023 Jul 10]. Reference Source\n\nSingh MK, Marshall B, Hawley J: Painful ophthalmoplegia: A case of tolosa–hunt syndrome. Mil. Med. 2014; 179(11): e1409–e1410. Publisher Full Text\n\nHeadache classification committee of the International Headache Society (IHS) the International Classification of Headache Disorders, 3rd Edition. Cephalalgia. 2018; 38(1): 1–211. PubMed Abstract | Publisher Full Text\n\nMahalingam HV, Mani SE, Patel B, et al.: Imaging spectrum of cavernous sinus lesions with histopathologic correlation. RadioGraphics. 2019; 39(3): 795–819. PubMed Abstract | Publisher Full Text\n\nSiddhanta KC, Shreeyanta KC, Kunwar P, et al.: Tolosa-Hunt Syndrome: A case report. J. Nepal Med. Assoc. 2021; 59(238): 604–607. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbdelrahman A: Case report: Tolosa Hunt Syndrome: A rare cause of painful ophthalmoplegia. [Dataset]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "247747",
"date": "21 Feb 2024",
"name": "Shreyashi Jha",
"expertise": [
"Reviewer Expertise Movement Disorders Neuroinfections Neuroimmunology"
],
"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 described a case of painful right lateral rectus palsy secondary to possible Tolosa Hunt Syndrome. However, I have some concerns: 1. Did patient have any past significant medical history? 2. Since the patient showed right abducens nerve palsy was raised ICT ruled out? What did the fundi show? 3. What do the authors mean by \"comprehensive metabolic panel\" and kindly enlist the \"autoimmune and vasculitic workup\" done? What was the CSF opening pressure? 4. Kindly include T1 contrast images for better clarity 5. What were the MRI findings of the patient when he had a recurrence of symptoms? Imaging should have been ideally repeated. 6. What do the authors mean by CSF analysis negative? 7. Was a CT chest and abdomen done? Were other neoplastic infectious and granulomatous causes including sarcoidosis excluded?\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? 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? Partly",
"responses": [
{
"c_id": "11369",
"date": "31 May 2024",
"name": "Amro Abdelrahman",
"role": "Author Response",
"response": "1. Did patient have any past significant medical history? No 2. Since the patient showed right abducens nerve palsy was raised ICT ruled out? What did the fundi show? CSF opening wasn't done (this point will be added to the next version as a limitation) however, Fundoscopic examination was normal. 3. What do the authors mean by \"comprehensive metabolic panel\" and kindly enlist the \"autoimmune and vasculitic workup\" done? What was the CSF opening pressure? comperensive metabolic panel includes both renal function test and liver function test 4. Kindly include T1 contrast images for better clarity I will try 5. What were the MRI findings of the patient when he had a recurrence of symptoms? Imaging should have been ideally repeated. imaging was not done on recurrence of symptoms (will be mention in case presentation) 6. What do the authors mean by CSF analysis negative? CSF showed no abnormalities (will be rephrased) 7. Was a CT chest and abdomen done? Were other neoplastic infectious and granulomatous causes including sarcoidosis excluded? CT chest and abdomen wasn't done"
},
{
"c_id": "12174",
"date": "20 Aug 2024",
"name": "Amro Abdelrahman",
"role": "Author Response",
"response": "Opening pressure was 17. (Added to the new version)"
}
]
},
{
"id": "290337",
"date": "28 Jun 2024",
"name": "Sanjay Mhalasakant Khaladkar",
"expertise": [
"Reviewer Expertise RADIOLOGY"
],
"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\n-Kindly provide results of tests done to rule out other causes of cavernous sinus involvement(Elaborate results of lab. investigations in short and how these helped in ruling out differential diagnosis)\n-images of contrast MRI, CT plain and contrast in region of interest.\n-Mention names after whom the entity is labelled.\n-Painful ophthalmoplegia- definition, causes.\n\n-Clinico-anatomical correlation\n-Role of thin T2 (early diagnosis),CT(rule out erosion, hyperostosis)\n-Any role of dynamic MRI?(early diagnosis)\n-Role of angiography/ MRangiography . -Similarity and how to differentiate from IgG4 related ophthalmic disease\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": "12175",
"date": "20 Aug 2024",
"name": "Amro Abdelrahman",
"role": "Author Response",
"response": "We did not address all points because our goal is a focused-case study of tolosa hunt disease. However new points were added: - Other neurons that could be affected - Differential diagnosis in (case presentation) - CT image"
}
]
}
] | 1
|
https://f1000research.com/articles/12-1594
|
https://f1000research.com/articles/12-1025/v1
|
22 Aug 23
|
{
"type": "Research Article",
"title": "Towards implementing telemedicine in Tunisia: Results of a knowledge, attitude and practice study among medical doctors",
"authors": [
"Mariem Nouira",
"Nesrine Souayeh",
"Nesrine Souayeh"
],
"abstract": "Background: The use of information and communication technology such as telemedicine occupies nowadays a huge place in modern medicine practice all over the world, mainly after the COVID-19 pandemic. However, its implementation in Tunisia and other developing countries has achieved little success with low utilization and can be challenging for several reasons. In this study, our aim was to assess the knowledge, attitudes and practice of Tunisian medical doctors regarding telemedicine. Methods: This was a cross-sectional web survey, administered to medical doctors in Tunisia in October 2022. Respondents’ level of knowledge of telemedicine was assessed by calculating a knowledge score (0 to 12). Attitude subsections were about perceived telemedicine attributes of relative advantage, compatibility, trial ability and complexity. Results: A total of 243 participants were included. The mean age was 45 ± 9.6 years old, and 57.2% were female, with a mean of 14.3 ± 10.3 years of professional experience. The majority (95.9%) had an average or high level of computer skills. More than half (59.3%) had a poor level of telemedicine knowledge. A good level of knowledge was significantly associated with age category over 50 years (p = 0.02) and with years of experience over 10 (p = 0.03). The majority (89.3%) had a moderate or high score about perceived advantages. The majority (88.5%) accepted use of telemedicine in their future practice. Almost half (46.9%) had practiced telemedicine activities before using a mobile phone (91%) or social media (64%). The principal limitations of applying telemedicine were challenges of organization and implementation, and incomplete patient examination. Conclusions: Although Tunisian doctors’ knowledge and practice of telemedicine were unsatisfactory, their positive attitude and willingness to try it in their future practice were encouraging. There is an urgent need for implementing telemedicine in Tunisia to improve health care coverage in some unprivileged areas.",
"keywords": [
"telemedicine",
"knowledge",
"attitude",
"medical informatics",
"Tunisia"
],
"content": "Introduction\n\nThe world is witnessing rapid advances in audiovisual and digital technologies. The availability of the Internet has enabled impressive gains in terms of time and distance. In light of all this progress, remote medicine is developing at an increasingly rapid pace.1\n\nInformation and communication technologies (ICTs) are playing an increasingly important and dominant role in the healthcare sector. They offer a multitude of solutions to the various difficulties encountered in the practice of medicine.2 Telemedicine, one of the most promising forms of ICT, is becoming an increasingly important part of modern medical practice, in response to the new needs and challenges in the health sector.3\n\nAlthough there is a wide variation in the definition of telemedicine, there is consensus on a broad conception of this field as the “delivery of personal and nonpersonal health services and of consumer and provider education as well as a means for safeguarding the living environment via information and communication technology (ICT)”.4\n\nThe health crisis caused by the COVID-19 pandemic highlighted the relevance and importance of telemedicine in the medical field. Greater use was made of the various forms of telemedicine during this pandemic. Telemedicine enabled equitable access to care for all socio-economic categories of patients, improved access to healthcare services for patients who were geographically isolated or had a loss of autonomy and facilitated coordination between different healthcare providers.5,6\n\nThe use of ICT in the medical and health care fields is very promising in terms of improving the quality and effectiveness of medical services.2 However, its implementation in Tunisia and other developing countries has achieved little success with low utilization and can be challenging for several reasons.5,6 Legal aspects of telemedicine use might be one of the major limitations of its generalization in our context. In Tunisia, the legal framework for the exercise of telemedicine has just been obtained following the publication of the presidential decree n°318/2022 in April 2022.7\n\nIn this study, our primary objective was to assess the knowledge and attitudes of Tunisian doctors regarding telemedicine. Our secondary objective was to determine the obstacles to the application of telemedicine.\n\n\nMethods\n\nThe study was a cross-sectional web survey. A Google Forms questionnaire was sent by email to a large sample of doctors (approximately 5,000 email addresses) during October 2022. Theses email addresses were obtained from the Union of General Practitioners and Specialists and from the email list of university doctors from the Faculty of Medicine of Tunis. Inclusion criteria were being a Tunisian graduate doctor (generalist or specialist) practicing in Tunisia in the public or private sector and agreeing to be part of the survey.\n\nWe collected baseline demographic information and characteristics (age, gender, years of experience, speciality, computer skills …) and different questions to evaluate telemedicine knowledge, attitudes, and practice.\n\nRespondents’ level of knowledge of telemedicine was assessed by questions to be answered in either “Yes” or “No.” A score of “1” was given for “Yes” and “0” for “No.” One can score a minimum of 0 and a maximum of 12 in this section. A knowledge score less than 6 was labeled as poor knowledge of telemedicine, and equal or more than a score of 6 was labeled as good knowledge of telemedicine.\n\nPerceived telemedicine attributes of relative advantage, compatibility, trial ability and complexity, were rated on a four-point Likert scale that ranged from “0 = strongly disagree” to “4 = strongly agree,” except for complexity attribute questions which were reversely scored (0 = strongly agree and 4 = strongly disagree). A total mean score was calculated for each subsection of attitude questionnaire (relative advantages, compatibility, trial ability and complexity). We considered a score of each subsection of attitudes ≤49% as low, 50–70% as average, and ≥71% as high.\n\nFor descriptive statistics, frequency and percentage values were calculated for categorical variables, and means (SD) values were used to describe continuous data.\n\nThe chi-square test was used to determine potential associations between the categorical groups. Statistical analysis was performed using SPSS software (version 23.0, IBM Corp). A p value ≤0.05 was considered as significant. Please see the underlying data.8\n\nAll participants were informed about the purpose of the study and were requested to participate in the study if they consented. All the information regarding the study was mentioned in the body text of the Google form and mail invitation. They were also informed about their right to refuse participation or drop out at any moment of the study collection process. All collected information and data analysis was confidential and anonymous during and after data collection. The approval of the ethics committee of Ben Arous Regional Hospital was obtained before conducting the study on 23 September 2022 with approval number 11/2022.\n\n\nResults\n\nIn total, 243 participants completed the questionnaire.\n\nTheir mean age was 45 ± 9.6 years old, and more than half (57.2%) were female, with a mean of 14.3 ± 10.3 years of professional experience. The majority (67.5%) were working in the public sector and were specialist physicians (79%) with a predominance of medical specialties (63.5%). More than half (53.9%) were hospital-university physicians. The majority worked between 31 to 50 hours per week (69.6%).\n\nRespondents’ sociodemographic characteristics are summarized in Table 1.\n\nMost participants (95.9%) had an average to high level of computer skills. More than half of respondents (53.5%) declared that they had a good Internet connection at work and a suitable place for the practice of telemedicine (58%). For the computer tools available in the workplace, most of them had access to a computer (86.8%) but didn’t have a headset (72.4%) or camera (56.8%).\n\nMost of the respondents had heard about telemedicine (98.4%) but more than half (56.8%) didn’t know the different fields of its application.\n\nThe most well-known telemedicine activity definition was teleconsultation (63.8%).\n\nOnly 39.1% of respondents had heard about the Tunisian telemedicine decree and 25.5% (62/243) had a little knowledge of content regulation.\n\nThe knowledge score mean value was 5.2 ± 3.5 points. More than half (59.3%) had a poor level of telemedicine knowledge. A good level of knowledge was significantly associated with the age category over 50 years (p = 0.02) and with over 10 years of experience (p = 0.03) (see Table 2).\n\nThe main information sources provided about telemedicine were media (TV, radio, social media) or colleagues (58.9%, N = 129 among 219 respondents).\n\nThe results of doctors’ attitudes toward telemedicine are summarized in Table 3.\n\nRelative advantages\n\nThe mean score of perceived relative advantages of telemedicine was 20.1 ± 6 points (ranging from 0 to 28). The majority (89.3%) had a moderate to high score relating to attitude about perceived advantages.\n\nMost participants agreed or strongly agreed that telemedicine was useful for the patient (82.3%), for the physician (81.5%) and for the health system in general (74.5%).\n\nMost participants agreed or strongly agreed that telemedicine improves access to health care (82.3%) and facilitates communication between healthcare professionals (86.4%).\n\nCompatibility\n\nThe mean score of perceived compatibility of telemedicine was 7.3 ± 2.8 points (ranging from 0 to 12). The majority (76.5%) had a moderate to high score relating to attitude about perceived compatibility.\n\nOnly 31.7% of respondents agreed or strongly agreed that telemedicine is compatible with their clinical practice.\n\nTrial ability\n\nThe mean score of perceived ability and motivation to try telemedicine (ranging between 0 to 28) was 21.5 ± 5 points. The majority (93%) had a moderate to high score relating to attitude about ability to try telemedicine.\n\nMost of the participants agreed or strongly agreed that they would like to receive training about telemedicine (86.8 %); they thought that telemedicine is useful in their practice (78.2%) and agreed to use telemedicine in their future practice (88.5%).\n\nComplexity/disadvantages\n\nThe mean score of complexity and disadvantages of telemedicine was 14.8 ± 4.9 points (ranging between 0 to 28). The majority (64.6%) had a moderate to high score relating to attitude regarding this aspect; they did not consider telemedicine as complex or having disadvantages.\n\nThe principal perceived advantages of applying telemedicine were patient interest (34.2%), tele surveillance (22.2%) and exchange of opinions between physicians (tele expertise) (20.6%).\n\nMost of respondents thought that telemedicine is the future of medical practice (70.8%), is a necessity (72%), is a hope (70.8%) and does not interest specialists only (84%). The majority declared that they were interested in telemedicine (83.5%).\n\nPerceived barriers to applying telemedicine\n\nThe principal perceived barriers to applying telemedicine were challenges of organization and implementation (84%), incomplete patient examination (80.7%), economic cost and remuneration (79.8%) and medico-legal aspects (79.8%) (see Figure 1). The practice sector (public or private) was significantly associated with challenges of organization and economic cost and remuneration barriers (p <10-3, p = 0.001, respectively). The obstacle relating to the lack of credibility with patients was found to be significantly associated with gender and age (p = 0.007, p = 0.01, respectively) (see Table 4).\n\nAlmost half (46.9%) of interrogated physicians had practiced telemedicine activities before, using a mobile phone (91%) or social media (64%). The majority among them (82.4%) had five years or more of professional experience; 55.3% were females; 59.6% were working in the public sector and 78.9% were specialists. There was no significant association between sociodemographic characteristics of the study population and practice of telemedicine.\n\nA total of 63.4% declared that they intended to use telemedicine in their future activity and 32.1% were undecided.\n\n\nDiscussion\n\nTelemedicine is finding an increasingly obvious place in optimizing curative, collegial, evidence-based and local medicine in societies that are experiencing a tangible digitalization. It is integrated as a key element in the evolution towards telehealth, which is supported by health management and integrates telecommunication systems and telecommunication technologies to protect and improve health.9\n\nThe use of ICT in health care systems is likely to be influenced by many factors. The main factor appears to be the availability of an Internet connection and the necessary equipment (computer, web camera, headsets, …) as well as a suitable place for telemedicine practice. In our study, most participants declared that they had a good Internet connection (53.5%), a suitable place to perform telemedicine (58%) and access to a computer (86.8%). However, the majority did not have the required accessories. In a French study carried out in 2017 among 278 physicians, although 84% declared that they had a good Internet connection, and 99.6% had access to a computer, only 34% had appropriate premises for the practice of telemedicine, and few had accessories (36% had a camera and 25% had a headset microphone).10\n\nAs for computer skills, most participants (95.9%) had an average to high level. Our findings were comparable to those of a recent study conducted in Libya, a neighbouring country, were only 26.6% of participants had professional computer skills, while 67.2% and 6.2% participants had average and beginner computer skill levels, respectively.11 These skills are highly important for implementing the use of telemedicine services. Therefore, we recommend software and computer skills training programs for physicians who are newly introduced to telemedicine technology, especially in transitional countries.\n\nAmong human-related factors influencing the use of telemedicine, components such as users’ knowledge and attitude towards technology are highly important.12 Several studies have shown that attitude and perception are important and key research questions to explain how telemedicine is viewed and conceived by health professionals.11,13 Our results showed that most Tunisian physicians have heard about telemedicine and the main sources of this information were media and colleagues. These findings were corroborated by the results of a large survey conducted in European countries and in Iran.14\n\nParticipants’ knowledge regarding telemedicine was unsatisfactory since only 39.1% of respondents had heard about the Tunisian telemedicine decree and 59.3% had a poor level of telemedicine knowledge. Our results were consistent with studies published in developing countries. In fact, only 37.6% of medical doctors in Ethiopia had good knowledge of telemedicine.12 Moreover, a cross-sectional study in India found similar results (41% had good knowledge).15 Therefore, our recommendation would be to initiate continuous professional development programs to improve the knowledge of health care professionals regarding telemedicine and its legislation in Tunisia.\n\nA good level of knowledge was significantly associated with the age category over 50 years (p = 0.02) and with years of experience over 10 (p = 0.03) in our study. These results were different from most studies. In fact, a cross-sectional Indian survey observed higher knowledge scores among MDs younger than 50-years-old.14 Moreover, Barton et al. found a significant difference in self-assessed knowledge and beliefs about telemedicine between the specialist physicians who were users of telemedicine and specialist physicians who were non-users of telemedicine.16\n\nMost of the participants in our survey had a positive attitude towards telemedicine and its perceived advantages. A survey in Michigan State University, USA, and other similar studies showed that the attitude of health care workers is an important factor in understanding and accepting telemedicine technologies.12,15,17–19 These facts are important, especially in countries struggling with implementing telemedicine in their routine practice, because attitude represents how telemedicine is perceived by health care workers. For such acceptance, program developers need to train health care workers and make the telemedicine programs usable for them.20\n\nFurthermore, the most cited advantages of telemedicine by Tunisian physicians were improving access to health care (82.3%) and facilitating communication between healthcare professionals (86.4%). The benefits of telemedicine were widely discussed in the literature, among them we found: promoting cooperation between public and private fields, reducing the waste of time and long trips for patients, resolving medical desert issues, treating isolated patients or those who cannot travel, adapting the supply of care to demographic changes and meeting the needs related to demographic changes and finally being able to respond to the growing number of patients suffering from chronic diseases.21–23 Moreover, qualitative studies emphasised the importance of economic gain when using telemedicine.21,22\n\nMost of our participants expressed their ability to try telemedicine in their future practice. In a large cross-sectional conducted in India, only 60% expressed interest in adopting this new technology in their future career.14 However, Ethiopian physicians were more open to trying telemedicine since 93.3% of them agreed or strongly agreed that trying telemedicine was a great opportunity and 81.9% of them would like to begin a telemedicine application.6\n\nThe majority of interrogated Tunisian doctors found telemedicine not complex and compatible with most of their practice aspects (64.6%). However, they expressed some serious concerns regarding the challenges of organization and implementation (84%), incomplete patient examination (80.7%), economic cost and remuneration (79.8%) and medico-legal aspects (79.8%). Moreover, only 31.7% thought that telemedicine was compatible with their clinical practice. The same concerns were expressed in other studies.6,15 Furthermore, new ethical issues have emerged from this type of medical practice regarding patients’ confidentiality.20 These findings indicate that much work is needed to be done to educate health care professionals about telemedicine and to lay the groundwork for successful and sustainable adoption of the technology in the country.6 In addition, appropriate training in ethical and medico-legal issues in telemedicine should reduce some of these concerns.15\n\nMoreover, other limitations to the implementation of telemedicine in limited resources countries deserve to be mentioned, such as technical issues and defective health care infrastructure restricting the potential for swift and innovative reforms.24–26\n\nAs for practicing telemedicine, 46.9% of interrogated physicians had practiced telemedicine activities before, using a mobile phone (91%) or social media (64%). This emphasises the need for creating a suitable common platform in order to properly practice telemedicine and therefore avoid some confidentiality issues relating to the use of the phone or social media.\n\nThis was the first Tunisian publication studying knowledge, attitudes, and practice of telemedicine among Tunisian practitioners. Our sample size was considerable, and we included all kinds of MD (public and private, specialist and non-specialist physicians). However, we did not take into consideration cultural aspects relating to telemedicine, or the patient’s perspective on the issue.\n\n\nConclusions\n\nIn conclusion, although Tunisian physicians’ knowledge level and practice of telemedicine were unsatisfactory, their positive attitude and willingness to try it in their future practice was encouraging. The Tunisian government should encourage this practice by providing telemedicine equipment and platforms on the one hand and offer the necessary training for health care providers on the other hand, in order to improve health care coverage in some underprivileged areas.\n\n\nConsent\n\nWritten informed consent for publication of the participants’ details was obtained from the participants.",
"appendix": "Data availability\n\nHarvard Dataverse: Underlying data for ‘Toward implementing telemedicine in Tunisia: Results of a knowledge, attitude and practice study among medical doctors’, “Telemedicine-Tunisia”, https://doi.org/10.7910/DVN/AAMOQN. 8\n\nThis project contains the following underlying data:\n\n• Date file 1: Telemedicine-Tunisia.xlsx (anonymised underlying data collected from medical doctors)\n\nHarvard Dataverse: Extended data for ‘Toward implementing telemedicine in Tunisia: Results of a knowledge, attitude and practice study among medical doctors’, “Telemedicine-Tunisia”, https://doi.org/10.7910/DVN/AAMOQN. 8\n\nThis project contains the following extended data:\n\n• Questionnaire: Telemedicine – English version.pdf\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\nThe authors want to thank the “Complementary studies in pedagogical and digital engineering Committee”, Faculty of Medicine of Tunis, for their support throughout the writing process. This study was carried out to obtain the certificate of complementary studies in pedagogical and digital engineering.\n\n\nReferences\n\nWaller M, Stotler C: Telemedicine: a Primer. Curr Allergy Asthma Rep. 2018 Aug 25; 18(10): 54. Publisher Full Text\n\nRyu S: Telemedicine: Opportunities and Developments in Member States: Report on the Second Global Survey on eHealth 2009 (Global Observatory for eHealth Series, Volume 2). Healthc Inform Res. 2012 Jun; 18(2): 153–155. Publisher Full Text\n\nBaker J, Stanley A: Telemedicine Technology: a Review of Services, Equipment, and Other Aspects. Curr Allergy Asthma Rep. 2018 Sep 26; 18(11): 60. PubMed Abstract | Publisher Full Text\n\nThrall JH, Boland G: Telemedicine in practice. Semin Nucl Med. 1998 Apr 1; 28(2): 145–157. Publisher Full Text\n\nWamala DS, Augustine K: A meta-analysis of telemedicine success in Africa. J Pathol Inform. 2013 Jan 1; 4(1): 6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBiruk K, Abetu E: Knowledge and Attitude of Health Professionals toward Telemedicine in Resource-Limited Settings: A Cross-Sectional Study in North West Ethiopia. J Healthc Eng. 2018 Nov 18; 2018: 1–7. Publisher Full Text\n\nDécret Présidentiel n° 2022-316 du 8 avril 2022, portant création d’une unité de gestion par objectifs à la Présidence du gouvernement pour la mise en place du projet de modernisation et généralisation des maisons de services et fixant son organisation et les modalités de son fonctionnement|DCAF Tunisie.[cited 2023 Jan 28]. Reference Source\n\nNouira MTelemedicine-Tunisia [Dataset]. Harvard Dataverse. 2023. Publisher Full Text\n\nWHO Group Consultation on Health Telematics (1997: Geneva S. A health telematics policy in support of WHO’s Health-for-all strategy for global health development: report of the WHO Group Consultation on Health Telematics, 11-16 December, Geneva, 1997.1998 [cited 2023 Jan 28]. Reference Source\n\nMesson T: Quelle est la place des médecins généralistes dans le développement de la télémédecine? Enquête auprès des médecins généralistes de Gironde. In 2017 [cited 2023 Jan 28].Reference Source\n\nElhadi M, Elhadi A, Bouhuwaish A, et al.: Telemedicine Awareness, Knowledge, Attitude, and Skills of Health Care Workers in a Low-Resource Country During the COVID-19 Pandemic: Cross-sectional Study. J Med Internet Res. 2021 Feb 25; 23(2): e20812. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAyatollahi H, Sarabi FZP, Langarizadeh M: Clinicians’ Knowledge and Perception of Telemedicine Technology. Perspect Health Inf Manag. 2015 Nov 1; 12(Fall): 1c. PubMed Abstract\n\nMairinger T, Gabl C, Derwan P, et al.: What do physicians think of telemedicine? A survey in different European regions. J Telemed Telecare. 1996 Mar 1; 2(1): 50–56. PubMed Abstract | Publisher Full Text\n\nZayapragassarazan Z: Awareness, Knowledge, Attitude and Skills of Telemedicine among Health Professional Faculty Working in Teaching Hospitals. JCDR. 2016 [cited 2023 Jan 28]; JC04. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nBarton PL, Brega AG, Devore PA, et al.: Specialist physicians’ knowledge and beliefs about telemedicine: a comparison of users and nonusers of the technology. Telemed J E Health. 2007 Oct; 13(5): 487–500. PubMed Abstract | Publisher Full Text\n\nOlok GT, Yagos WO, Ovuga E: Knowledge and attitudes of doctors towards e-health use in healthcare delivery in government and private hospitals in Northern Uganda: a cross-sectional study. BMC Med Inform Decis Mak. 2015 Nov; 15(15): 87. Publisher Full Text\n\nIdowu PA, Adagunodo ER, Idowu AO, et al.: Electronic referral system for hospitals in Nigeria. IFE J Sci. 2004; 6(2): 161–166.\n\nParvin R, Shahjahan M: Knowledge, Attitude and Practice on eHealth Among Doctors Working at Selected Private Hospitals in Dhaka, Bangladesh. J Int Soc Telemed eHealth. 2016 Sep 22; 4: e15 (1-11).\n\nWhitten P, Holtz B, Nguyen L: Keys to a successful and sustainable telemedicine program. Int J Technol Assess Health Care. 2010 Apr; 26(2): 211–216. PubMed Abstract | Publisher Full Text\n\nPresseau J, Sniehotta FF, Francis JJ, et al.: Multiple goals and time constraints: perceived impact on physicians’ performance of evidence-based behaviours. Implement Sci. 2009 Nov 26; 4(1): 77. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLombardo F: La télémédecine en médecine générale: évaluation du point de vue et du ressenti des médecins généralistes. [thèse: médecine]. Paris: Université Pierre et Marie Curie.2013.\n\nCarré E: Télémédecine: représentations et expériences des médecins généralistes: Étude qualitative menée auprès de médecins généralistes du Languedoc-Roussillon.\n\nMathieu S: La téléconsultation: l’avis des médecins généralistes dans les Alpes Maritimes. [thèse: médecine]. Sophia Antipolis: Université de Nice-Sophia Antipolis.2012.\n\nXu H, Huang S, Qiu C, et al.: Monitoring and Management of Home-Quarantined Patients With COVID-19 Using a WeChat-Based Telemedicine System: Retrospective Cohort Study. J Med Internet Res. 2020 Jul 2; 22(7): e19514. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLonergan PE, Iii SLW, Branagan L, et al.: Rapid Utilization of Telehealth in a Comprehensive Cancer Center as a Response to COVID-19: Cross-Sectional Analysis. J Med Internet Res. 2020 Jul 6; 22(7): e19322. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAngood MD, Peter B: Telemedicine, the Internet, and World Wide Web: Overview, CurrentStatus, and Relevance to Surgeons. World J Surg. 2001 Nov 1; 25(11): 1449–1457. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "257775",
"date": "07 May 2024",
"name": "Benson Ncube",
"expertise": [
"Reviewer Expertise Digital health strategy and initiatives"
],
"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. General, The authors are discussing an important aspect in the field of telemedicine. This is a quite relevant topic and they are commended for their work. Albeit some comments are presented to redeem this manuscript.\n2. In the topic, I suggest the authors consider deleting the words \"Results of a\", because we know they are presenting the results.\n3. Abstract. The sample size must be stated in this section.\n4. Introduction. What about \"cloud and mobile computing?\"In para 2, The use of ICTs is not only dominant in the health sector. \"Telemedicine, one of the most promising forms of ICT,\" This is not a true statement. Rephrase. In para 3, I suggest you use the current definition of telemedicine by WHO. In para 5, please cite more African cases, eg. Botswana, South Africa, Egypt, Lybia, etc. There are plenty of such cases. A little bit of explanation of the presidential decree will give a better understanding to the reader. Authors are requested to provide a more detailed context on where the study took place. What is the land size of Tunisia? population of the general public? how is the health system structured in Tunisia? What is the doctor/patient ratio? Compare this ratio with the recommended WHO ratio for Tunisia. How is the mobile phone penetraition rate, and the affordability of mobile phone services?\n5. Methods. I suggest authors give a detailed description of the Questionnaire, in terms of types and number of questions, e.g. Likert, dichotomous, open-ended, closed questions. What is the sample size? Authors should be very clear on this, as they know exactly how many participants they sampled. Determine and present the response rate of participants. Your design of the study needs to be clearly articulated, to cover the sample size, sampling strategy, inclusion/exclusion criteria, and data analysis methods used. Discuss the use of statistics in the design. The results of the analysis should be presented in the Results section.\nThere is a need to present your Chi-square Test results, in order to help the reader to understand your presented results.\n6. Results. In Table 2, why is it that some p-values are not presented? Inclusion of all p-values will make your table more complete. On page 5, where authors report statistically significant results, they should provide the statistics (Chi-square value), degree of freedom for the contigence table together with the p-value. This is the proper way of reporting this kind of result.\nIn Fig 1, you use the word \"Main\", which are the minor barriers then? When reporting under the sub-heading \"Perceived barriers ....\" you used percentages which is a repetition of results since they are already reported in Fig. 1.\nIn sub-topic \"Practice\" you need to use items in the same class\" So in the first sentence, you cannot use \"mobile phone\" but \"mobile phone application\"\n\n7. Discussion. In the first paragraph, I suggest you add \"in healthcare\" at the end of the first sentence. Replace \"our\" with \"this\" as we know it is your study. It would appear there is an over use of the word \"declared\" throughout the paper. Please find alternatives. In the third paragraph replace were with where. In this paragraph, it will be interesting to compare your results with those of other countries like Botswana, Egypt, Nigeria, Pakistan, Ethiopia. (Ref-1). Do the same in paragraphs 4 & 5. In the subsequent paragraphs, I suggest you extract all your recommendations and put them under a sub-topic \"Recommendations\".\n\nIn paragraph 3, what about referrals, access to special services, and seeking or giving second opinion? You did not consider COVID-19 aspects? In paragraph 6, is the term \"limited resources countries\" or \"resource limited countries\"? In paragraph 7, an ambiguous clause is noted - using a mobile phone (91%) or social media (64%).\nIn the section, limitations of the study, what about the following? You did not consider the diversity of healthcare workers, those without access to the Internet.\n8. Conclusion. Should the government provide equipment and telemedicine platforms? Or must create the enabling environment, develop strategy and policies for telemedicine, and set up regulations?\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12171",
"date": "01 Oct 2024",
"name": "Mariem Nouira",
"role": "Author Response",
"response": "Dear Dr Benson Ncube, Thank you very much for your review. We really appreciate your response and time. We have revised our manuscript as you suggested. Here are the responses to your comments: Reviewer comment: In the topic, I suggest the authors consider deleting the words \"Results of a\", because we know they are presenting the results. Author response: It was corrected. Thank you “Towards implementing telemedicine in Tunisia: A knowledge, attitude and practice study among medical doctors” Reviewer comment: Abstract. The sample size must be stated in this section. Author response: We didn’t calculate the sample size because we didn’t have the results of a Tunisian study that was conducted previously using the same questionnaire to use the parameters to calculate the sample size. Also, we didn’t find in the literature a specific formula to calculate sample size of Knowledge Attitude and Practice studies. Reviewer comment: Introduction. What about \"cloud and mobile computing?\"In para 2, The use of ICTs is not only dominant in the health sector. \"Telemedicine, one of the most promising forms of ICT,\" This is not a true statement. Rephrase. In para 3, I suggest you use the current definition of telemedicine by WHO. In para 5, please cite more African cases, eg. Botswana, South Africa, Egypt, Lybia, etc. There are plenty of such cases. A little bit of explanation of the presidential decree will give a better understanding to the reader.Authors are requested to provide a more detailed context on where the study took place. What is the land size of Tunisia? population of the general public? how is the health system structured in Tunisia? What is the doctor/patient ratio? Compare this ratio with the recommended WHO ratio for Tunisia. How is the mobile phone penetraition rate, and the affordability of mobile phone services? Author response: All suggested modifications were done thank you. Reviewer comment: Methods. I suggest authors give a detailed description of the Questionnaire, in terms of types and number of questions, e.g. Likert, dichotomous, open-ended, closed questions. Author response: All suggested modifications were done thank you. Reviewer comment: Results. In Table 2, why is it that some p-values are not presented? Inclusion of all p-values will make your table more complete. On page 5, where authors report statistically significant results, they should provide the statistics (Chi-square value), degree of freedom for the contigence table together with the p-value. This is the proper way of reporting this kind of result. Author response: The p-values of all variables (one p for each variable) were presented in the table 2. All other suggested modifications were done. Thank you. Reviewer comment: In Fig 1, you use the word \"Main\", which are the minor barriers then?When reporting under the sub-heading \"Perceived barriers ....\" you used percentages which is a repetition of results since they are already reported in Fig. 1. In sub-topic \"Practice\" you need to use items in the same class\" So in the first sentence, you cannot use \"mobile phone\" but \"mobile phone application\" Author response: All suggested modifications were done thank you. Reviewer comment: Discussion. In the first paragraph, I suggest you add \"in healthcare\" at the end of the first sentence. Replace \"our\" with \"this\" as we know it is your study. It would appear there is an over use of the word \"declared\" throughout the paper. Please find alternatives. In the third paragraph replace were with where. In this paragraph, it will be interesting to compare your results with those of other countries like Botswana, Egypt, Nigeria, Pakistan, Ethiopia. (Ref-1). Do the same in paragraphs 4 & 5. In the subsequent paragraphs, I suggest you extract all your recommendations and put them under a sub-topic \"Recommendations\". Author response: All suggested modifications were done thank you. Reviewer comment: In the section, limitations of the study, what about the following? You did not consider the diversity of healthcare workers, those without access to the Internet. Author response: All suggested modifications were done thank you. Reviewer comment: Conclusion. Should the government provide equipment and telemedicine platforms? Or must create the enabling environment, develop strategy and policies for telemedicine, and set up regulations? Author response: All suggested modifications were done thank you very much."
}
]
},
{
"id": "281821",
"date": "26 Jun 2024",
"name": "Sumaiah Alrawiai",
"expertise": [
"Reviewer Expertise My research topics include patient-centered care",
"shared decision-making",
"and patient-doctor communication. I've done some studies in digital health as well."
],
"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 paper that aims to explore the knowledge, attitudes, and practice of telemedicine by doctors in Tunisia. However, there are some issues that need to be addressed and they are presented here:\nThe introduction could benefit from additional information on the current healthcare landscape in Tunisia and how telemedicine could help. What are the possible barriers and facilitators to adopting telemedicine in Tunisia, or if not available, countries with similar healthcare system to Tunisia? Towards the end of the introduction, the objective was stated but it was missing the practice part. Only knowledge and attitudes were mentioned. The methods section is missing some information. How did you develop the questionnaire? Was it adopted from another study, or was it developed by the authors? If developed by authors, how did you develop it, and what were the sources used? If it was adopted from another study, then please reference the source. Also, in the methods section, when sending the invites, did you send any reminders, and were there any differences between those who responded and those who didn’t? Was the sample size enough? How did you ensure that? If the questionnaire was developed by the authors, how did you ensure the validity and reliability of the questionnaire? Under the discussion, some areas would benefit from an in-depth analysis of why there was a difference or a similarity between your study and other studies.\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?\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": "12172",
"date": "20 Aug 2024",
"name": "Mariem Nouira",
"role": "Author Response",
"response": "Dear Dr Sumaiah Alrawiai, Thank you very much for your review. We really appreciate your response and time. We have revised our manuscript as you suggested. Here are the responses to your comments: Reviewer comment: The introduction could benefit from additional information on the current healthcare landscape in Tunisia and how telemedicine could help. What are the possible barriers and facilitators to adopting telemedicine in Tunisia, or if not available, countries with similar healthcare system to Tunisia? Author response: The introduction was modified. For the barriers to adopting telemedicine in Tunisia, it was the secondary objective of our study, and it was responded in the result section. It was also discussed in the discussion. Thank you. Reviewer comment: Towards the end of the introduction, the objective was stated but it was missing the practice part. Only knowledge and attitudes were mentioned. Author response: It was corrected. Thank you Reviewer comment: The methods section is missing some information. How did you develop the questionnaire? Was it adopted from another study, or was it developed by the authors? If developed by authors, how did you develop it, and what were the sources used? If it was adopted from another study, then please reference the source. Author response: The questionnaire was developed essentially by the authors, and it was partly inspired from a study conducted in Ethiopia that was cited. Thank you. Reviewer comment: Also, in the methods section, when sending the invites, did you send any reminders, and were there any differences between those who responded and those who didn’t? Was the sample size enough? How did you ensure that? Author response: We did not send reminders. And we didn’t have information about the non responders so we can’t compare them with the responders. We didn’t calculate the sample size because we didn’t have the results of a Tunisian study that was conducted previously using the same questionnaire to use the parameters to calculate the sample size. Also, we didn’t find in the literature a specific formula to calculate sample size of Knowledge Attitude and Practice studies. Reviewer comment: If the questionnaire was developed by the authors, how did you ensure the validity and reliability of the questionnaire? Author response: The reliability and validity of the questionnaire was not studied in our manuscript. It could constitute the aim of another manuscript. Thank you. Reviewer comment: Under the discussion, some areas would benefit from an in-depth analysis of why there was a difference or a similarity between your study and other studies. Author response: The discussion was enhanced and modified. Thank you very much."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1025
|
https://f1000research.com/articles/11-1206/v1
|
24 Oct 22
|
{
"type": "Case Report",
"title": "Case Report: Tropical sprue, diagnostic challenges of an old but unrecognized disease",
"authors": [
"Jihene Guissouma",
"Hana Ben Ali",
"Hend Allouche",
"Insaf Trabelsi",
"Olfa Hammami",
"Yosra Yahia",
"Ilhem Mchirgui",
"Marwa Mabrouk",
"Hatem Ghadhoune",
"Hana Ben Ali",
"Hend Allouche",
"Insaf Trabelsi",
"Olfa Hammami",
"Yosra Yahia",
"Ilhem Mchirgui",
"Marwa Mabrouk",
"Hatem Ghadhoune"
],
"abstract": "Tropical sprue (TS) is a post-infective disease of the small bowel characterized by a malabsorption syndrome affecting tropics inhabitants and visitors. Diagnosis of TS remains challenging since it can be confused with common diarrheal diseases, especially in non-endemic areas. We report a Tunisian case of latent TS. A 58-year-old male with a history of chronic watery diarrhea, was admitted to the intensive care unit for confusion which was related to a severe metabolic acidosis. Despite the neurological improvement after hydro-electrolytic resuscitation and acid-base disorders correction, the patient continued to have three to five loose stools daily. A nutritional assessment showed a malabsorption syndrome: iron, Vitamin B12and folate deficiencies; normochromic normocytic anemia and hypoalbuminemia. Gastrointestinal endoscopy showed duodenal villous atrophy and biopsy confirmed subtotal villous atrophy with increased intraepithelial lymphocytosis and a thickened hyalonalized sub-epithelial basal lamina. Celiac disease was evoked, however the patient did not improve on a gluten-free diet and the celiac serology was negative. On re-interviewing, we discovered that the patient had spent two months in India three years prior. Given the travel history, clinico-biological and histological data TS was highly considered and a good response to a five-month antibiotic course combined to nutritional supplementation supported this diagnosis. Clinico-biological, endoscopic and histological findings were overlapping between TS and other malabsorption diseases, explaining diagnosis difficulties. TS should be systematically discussed in tropics visitors presenting with chronic diarrhea. Improvement after micronutrient and vitamin deficiencies replacement combined to a prolonged antibiotic course supports the diagnosis of TS.",
"keywords": [
"Chronic diarrhea",
"small bowel disease",
"malabsorption",
"tropical sprue",
"villous atrophy."
],
"content": "Introduction\n\nTropical sprue (TS) is a very old disease. The first reported cases were described by a Yorkshireman, Dr William Hillary, among the inhabitants of the island of Barbados over 200 years ago.1 Endemic TS occurs in the tropical and subtropical regions but is underrecognized elsewhere. It is predominantly present in southern and southeast Asia and the Caribbean Islands, and rarely described in North Africa and Europe. Within the present era of globalization and worldwide travel, it is important for all clinicians to be aware of the possibility of TS in patients presenting with diarrhea, malabsorption, multiple nutritional deficiencies and mucosal abnormalities in the small bowel who have travelled to endemic regions.2\n\nDiagnosis of TS remains challenging since it can be confused with common diarrheal diseases, including celiac disease, Crohn’s disease, bacterial overgrowth, and other infectious aetiologies.3\n\nIn this article, we present a Tunisian case of latent TS revealed by a confusional syndrome.\n\n\nCase report\n\nA 58-year-old North African male was admitted to the intensive care unit for confusion without fever. He was single, working as a trader and had a history of iron deficiency anemia. There were no particular family antecedents. The acute symptoms had been preceded by chronic diarrhea, worsening fatigue, and a 40 pounds weight loss over three years which were trivialized by the patient. He had neither HIV nor tuberculosis risk factors.\n\nPhysical examination revealed conjunctival pallor, diffuse abdominal pain and dehydration without fever or organomegaly. Blood glucose levels were normal, as well as the urine dipstick.\n\nBlood tests identified metabolic acidosis (Ph = 7.35, paCO2 = 22.9 mmHg, HCO3- = 12.9 mmol/L, paO2 = 88 mmHg) with normal anion gap which was related to gastrointestinal loss of bicarbonate. We also noted normochromic normocytic anemia (haemoglobin = 5.7 g/dL, MCV = 81 fl, MCHC = 30 g/dL), and normal WBC (7200/μL) and platelet (174000/μL) counts. Renal and liver functions were correct (creatinine = 72 μmol/L, total bilirubin = 13.6 μmol/L, AST/ALT/ALP = 31/31/140 IU/L). The blood ionogram showed hypokalaemia (2.81 mmol/L) and hypophosphatemia (0.32 mmol/L) with normal natremia (139 mmol/L) and chloremia (110 mmol/L). Additional investigations revealed normal level of vitamin B1, negative viral serologies (Hbs, HCV and HIV) and negative toxicology work-up. Brain MRI and abdominal CT scan were normals.\n\nThe most likely cause of confusion was the severe metabolic acidosis after ruling out cerebral causes, toxic causes, uraemia, hepatic encephalopathy, and Gayet wernicke encephalopathy (no chronic alcoholism, no diabetes history and normal level of vitamin B1). Furthermore, we noted an improvement on the state of consciousness after hydro-electrolytic resuscitation and acid-base disorders correction. Despite the neurological improvement, the patient continued to have watery diarrhea, abdominal meteorism and weight loss. Thus, he was treated for a possible small bowel bacterial overgrowth with an association of a third generation cephalosporin and metronidazole. However, he continued to have three-five loose stools daily.\n\nA nutritional assessment was performed and showed a malabsorption syndrome: iron deficiency (ferritin = 0.84 μg/L, serum iron = 2.44 μmol/L), hypoalbuminemia (22 g/L) and hypocalcaemia (1.8 mmol/L). We also noticed slight deficiencies in Vitamin B12: 170 pg/mL (normal: 180-914 pg/mL) and folate: 3.2 μg/L (normal > 3.5 μg/L).\n\nUpper gastrointestinal endoscopy showed partial villous atrophy (Figure 1). These changes were nonspecific but were suggestive of celiac disease. Thus, a gluten-free diet was prescribed.\n\nDuodenal biopsy showed subtotal villous atrophy with increased intraepithelial lymphocytosis and a very thickened hyalonalized sub-epithelial basal lamina: an appearance suggestive of sprue (Figure 2).\n\nOn re-interviewing, we discovered that the patient had spent two months in India (for commercial purposes) three years prior. A few months after his return, he developed chronic intermittent watery, non-bloody diarrhea. He was also experiencing asthenia and had a weight loss but he did not consult any doctor.\n\nCeliac serologies, including endomysial antibody, tissue transglutaminase antibody, and gliadin IgA, gliadin IgG, and total IgA levels were all negative. In light of these negative serologies and lack of response to a gluten-free diet, celiac disease was unlikely. Given the travel history, clinico-biological, endoscopic and histological findings, TS was highly considered.\n\nA five-month antibiotic course was prescribed (tetracycline 250 mg four times daily) combined to a nutritional supplementation (iron: 150 mg and folate: 5 mg orally daily with cyanocobalamin 1000 μg daily intramuscularly for ten days, followed by 1000 μg monthly for one year). Within one month the patient reported feeling significantly better with resolution of diarrhea, increased energy and weight gain. The biochemical parameters had normalized at the three-month check-up (haemoglobin = 9.4 g/dL, and albumin = 43 g/L). The response to treatment supported the diagnosis of TS.\n\nOn the one-year follow-up visit, the patient was continuing to improve. He gained 35 pounds of weight and the diarrhea was completely gone.\n\n\nDiscussion\n\nThe main strengths associated to this case report of TS were: the uncommon presentation of TS which was revealed by a confusional syndrome; and the clinico-biological, endoscopic and histological features supporting this rare and unrecognized diagnosis in non-endemic areas. Response to combined treatment confirmed the diagnosis but the lack of an endoscopic control after improvement was a limitation in our case. In fact, TS is a disease of the small intestine characterized by a malabsorption syndrome with a subtotal or partial mucosal atrophy. It occurs mainly in the tropics, particularly in most of the Greater Antilles, the northern part of South and Central America and South-East Asia. It appears to be rare in Africa, but its real frequency is unknown as small bowel biopsies are not routinely done.4 TS affects indigenous inhabitants and expatriates, either long-term residents or short-term visitors, in these endemic areas (the case of our patient).4,5 Patients can present with diarrhea soon after returning from the tropics, but rarely TS may be latent for months to years after leaving the endemic region, as was the case of our patient.6\n\nThe risk factors involved in the pathogenesis of this small bowel disease are immune deficiency, poor hygiene, and bacterial, viral or parasitic gastrointestinal infections.3 In fact, the most incriminated bacteria are Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae.7,8 Enterotoxin production by some strains of enterotoxigenic K. pneumonia or E. coli can lead to abnormalities of mucosal structure and function.4 Otherwise, the local action of unabsorbed bile acids might also be involved.3\n\nThe diagnosis of TS is difficult. It is based on the combination of clinico-biological, histological and evolutionary criteria:3,7,9\n\n• Compatible clinical presentation: diarrhea, weight loss, asthenia,\n\n• Evidence of a malabsorption syndrome of two unrelated substances,\n\n• Abnormal small intestinal mucosal histology,\n\n• Exclusion of other intestinal diseases with similar presentation,\n\n• Improvement after treatment with tetracycline and folic acid.\n\nTherefore, TS must be considered in patients who have lived in an endemic area, presenting with chronic diarrhea and evidence of malabsorption. Megaloblastic anemia is common and is secondary to folate and vitamin B12 deficiencies. Associated iron deficiency may turn a macrocytic anemia into a normocytic anemia. This could explain the normochromic normocytic anemia of our patient further, since he had a history of iron deficiency anemia. Calcium, vitamin D and magnesium-impaired absorption may also occur, with resulting osteopenia. Steatorrhea is often evident if fecal fat is measured. Furthermore, abnormal D-xylose test supports proximal small intestine malabsorption.3,4,6,9,10\n\nGastrointestinal endoscopic findings are non-specific in TS. In fact, celiac disease must be considered, especially given the endoscopic abnormalities and histological similarity with TS.8 Biopsy from the distal portion of the duodenum reveals villous atrophy and an increased infiltration of the lamina propria by chronic inflammatory cells (plasma cells and lymphocytes).8 Other causes of malabsorption (celiac disease, Crohn’s disease, bacterial overgrowth and lymphoma) must be ruled out.3,4,9\n\nThe key principles in the management of TS include rehydration, micronutrient deficiency replacement, oral folate, intramuscular vitamin B12 and antibiotics. Sulfonamides and, more recently, new quinolones, particularly ofloxacin, were tried in some previous cases reported in the literature. However, tetracycline is the antibiotic of choice, administered at a dose of 250 mg orally four times daily.3,4,8,9,11 The duration of treatment has not yet been codified, as it depends on the evolution of the disease. In general, it’s a prolonged antibiotic course over three to six months. It will be stopped after control of the restitution ad integrum of the clinico-biological and histological anomalies.8,9,12 In our case, tetracycline was prescribed for five months and the favourable response to treatment supported the diagnosis of TS, but a control by gastrointestinal endoscopy wasn’t carried out.\n\nComplete resolution after an optimal management is standard in the returning travellers from an endemic area. However, for the tropics inhabitants, TS may relapse, requiring a prolonged follow-up given the risk of re-exposure to the infectious agent.3,6,8,12\n\n\nConclusions\n\nClinico-biological, endoscopic and histological findings overlap between TS and other malabsorption diseases, explaining diagnosis difficulties. While TS is common in tropics inhabitants, it must be considered in tropics visitors presenting with chronic diarrhea after ruling out other causes. Improvement after an optimal management combining rehydration, replacement of micronutrient, folate and vitamin B12 deficiencies as well as a prolonged antibiotic course supports the diagnosis of TS.\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\n\nConsent\n\nWritten informed consent for publication of the clinical details and clinical images was obtained from the patient.",
"appendix": "References\n\nBartholomew C: William Hillary and sprue in the Caribbean: 230 years later. Gut. 1989; 30 Spec No: 17–21. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlipstein FA, Baker SJ: Regarding the definition of tropical sprue. Gastroenterology. 1970; 58: 717–721. PubMed Abstract | Publisher Full Text\n\nGhoshal UC, Srivastava D, Verma A, et al.: Tropical Sprue in 2014: the New Face of an Old Disease. Curr. Gastroenterol. Rep. 2014; 16(6): 391. PubMed Abstract | Publisher Full Text\n\nKlipstein FA: Tropical sprue in travelers and expatriates living abroad. Gastroenterol. 1981; 80: 590–600. PubMed Abstract | Publisher Full Text\n\nPrendki V, Grandière-Perez L, Ansart S, et al.: Tropical sprue in two foreign residents, with evidence of Tropheryma whippelii in one case. Travel Med. 2006; 13: 175–177. PubMed Abstract | Publisher Full Text\n\nRamakrishna BS, Venkataraman S, Mukhopadhya A: Tropical malabsorption. Postgrad. Med. J. 2006; 82: 779–787. PubMed Abstract | Publisher Full Text\n\nRanjan P, Ghoshal UC, Aggarwal R, et al.: Etiological spectrum of sporadic malabsorption syndrome in northern Indian adults at a tertiary hospital. Indian J. Gastroenterol. 2004; 23: 94–98.\n\nWestergaard H: Tropical Sprue. Curr. Treat. Options Gastroenterol. 2004; 7(1): 7–11. Publisher Full Text\n\nMacaigne G, Boivin JF, Auriault ML, et al.: Sprue tropicale: à propos de 2 cas observés dans la région parisienne. Gastroenterol. Clin. Biol. 2004; 28: 913–916. Publisher Full Text\n\nKlipstein FA, Corcino JJ: Factors responsible for weight loss in tropical sprue. Am. J. Clin. Nutr. 1977; 30: 1703–1708. PubMed Abstract | Publisher Full Text\n\nWalker MM: What is tropical sprue? J. Gastroenterol. Hepatol. 2003; 18: 887–890. Publisher Full Text\n\nRickles FR, Klipstein FA, Tomasini J, et al.: Long-term follow-up of antibiotic-treated tropical sprue. Ann. Intern. Med. 1972; 76: 203–210. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "178343",
"date": "20 Jun 2023",
"name": "Wolfgang Kreisel",
"expertise": [
"Reviewer Expertise Gastroenterology. Infectious Diseases. Celiac 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\nTropical sprue is a frequent cause of malassimilation syndrome in tropical countries accounting for up to 30% of affected persons. However, it is rare in Europe, North America, or Countries lining the Mediterranean Sea. The authors describe the case of a 58-years-old male patient who presented with confusion, dehydration, and watery diarrhea in a University Hospital in Tunisia. Clinical presentation, endoscopy of the duodenum, and thorough anamnestic evaluation (the patient spent 2 months in India), and response to antibiotic therapy led to the correct diagnosis of tropical sprue. The paper is very interesting, and it is well written. However, I recommend stylistic editing for English language and grammar.\nSeveral items should be corrected or changed:\nThe patients had only a mild metabolic acidosis, not a severe acidosis. The blood pH of 7.35 is at the lower limit of normal. Please indicate base excess and exact value for anion gap. Metabolic acidosis with normal anion gap proves bicarbonate loss, as the authors indicate. The confusion is rather the consequence of dehydration that the consequence of the mild (!) acidosis. The hypokalemia of 2.81 mMol/L in acidosis is a dangerous situation.\n\nFurther blood tests clearly indicated malassimilation syndrome, as was further demonstrated by the evidence of villous atrophy. The authors use the term “hyalonalized”. Is this a generally accepted term? Should it be “hyaluronalized”? Amorphic material beneath the basal membrane resembling hyaluronic acid?\n\nI suggest to better discuss the differential diagnosis of villous atrophy (celiac disease, refractory celiac disease, autoimmune enteropathy, post-infectious villous atrophy etc.). Was giardiasis excluded, or other intestinal pathogens?\n\nTherapy and clinical course are correct described.\n\nAs for refs., I recommend to add few newer reviews, e.g. Louis-Auguste & Kelly (2017)1;. Green et al., (2022)2.\nThe manuscript may be approved with reservations.\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? Yes",
"responses": [
{
"c_id": "10143",
"date": "13 Sep 2023",
"name": "Jihene Guissouma",
"role": "Author Response",
"response": "Dear Reviewer Thank you for accepting to review this article. We agree that the metabolic acidosis wasn’t severe in our case. The base excess and the anion gap values were -9,9 and 16 respectively. We corrected the term hyalonalized with hyalinized. We have better discussed the differential diagnosis. In fact, bacterial overgrowth was unlikely as the coprocultrure were negative and the patient didn’t improve after antibiotherapy. Unfortunately, parasitological stool testing wasn’t available in our laboratory. Autoimmune enteropathy was unlikely as no extra-intestinal manifestation were documented. Furthermore, medication-induced enteropathy was not discussed since the patient wasn’t under any treatment. Although seronegative celiac disease is rare but possible our patient didn’t improve after gluten free diet which was another argument against this diagnosis. We added the new reviews recommended."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1206
|
https://f1000research.com/articles/13-939/v1
|
20 Aug 24
|
{
"type": "Research Article",
"title": "Effectiveness of men in maternity health (MiM) intervention on male involvement in maternal health care to improve maternal health outcomes in Naypyitaw, Myanmar",
"authors": [
"May Chan Oo",
"San San Myint Aung",
"Pyae Linn Aung",
"Alessio Panza",
"May Chan Oo",
"San San Myint Aung",
"Pyae Linn Aung"
],
"abstract": "Background Maternal health care (MHC) is critical for safe motherhood and preventing maternal deaths in Myanmar, but the institutional delivery rates are not yet optimal, increasing preventable maternal deaths. To address this issue, involving men in supporting MHC has been recognized as a strategy to improve MHC outcomes. This study aimed to assess the effectiveness, acceptability, and feasibility of men in maternity health (MiM) intervention on male involvement in MHC and its influence on knowledge, attitudes, and practices related to maternal health and institutional delivery rates in Naypyitaw, Myanmar.\n\nMethods This study employed a mixed-methods approach with quantitative surveying of the male partners and qualitative interviewing of both male and female partners and health stakeholders. A 6-month MiM education program on pregnancy complications, antenatal care, delivery care, and birth preparedness was provided to the intervention group. Before and after the intervention, comparisons between intervention and control groups were made.\n\nResults The socio-demographic characteristics of male partners were comparable between the intervention and control groups during the pre-intervention assessment. Before MiM intervention, notable differences in male partners’ knowledge, attitudes, birth preparedness and complication readiness practices regarding MHC were not evident between these two groups. After completing the MiM, significant score improvement, including higher ID rates compared to the control group (p<0.001), was observed. The acceptability and feasibility of the MiM program were contributed by positive responses from qualitative findings, highlighting remarkable changes in the perspectives of male partners in supporting MHC. However, challenges, including financial limitations, cultural influences and a shortage of trained personnel, were encountered.\n\nConclusion The MiM program effectively promotes male involvement in MHC, leading to improved MHC outcomes. The MiM intervention offers a promising, evidence-based model to enhance ID rates in Myanmar, requiring tailored approaches to address cultural and financial factors.",
"keywords": [
"Maternal health care",
"Myanmar",
"Men in maternity health",
"Male partner",
"Institutional delivery"
],
"content": "Introduction\n\nThe aim of maternal health care (MHC) is to improve the well-being of pregnant women, reduce potential complications, and ensure safe delivery and recovery by means of continuous medical support throughout pregnancy, childbirth, and postnatal phase.1–4 Enhancing maternal health (MH) is ‘target 3.1: good health and well-being’ of the Sustainable Development Goals and countries employ various strategies to accomplish this target.1\n\nIn 2020, approximately 287,000 maternal deaths occurred globally due to causes related to pregnancy and childbirth, which means about 800 women dying daily or one lost every two minutes. Almost 95% of deaths occurred in low and lower-middle-income countries, and the Asia Region accounted for a quarter of them.5 Myanmar, one of the Asia Region, reported 1,700 maternal deaths in 2020. This reflects Myanmar having one of the highest maternal mortality ratios (MMR) at a rate of 179 per 100,000 births compared to the global MMR of 223 per 100,000 live births.6 Despite ongoing efforts, most of these preventable deaths persist, especially in resource-limited settings.6–8\n\nIn recent years, Myanmar has made efforts towards improving the utilization of MHC services, but there are still gaps that need addressing. According to the 2015-2016 national demographic survey, 95% of pregnant women received antenatal care (ANC) by skilled health care providers at least once, but 63% received the recommended minimum of four ANC visits. Furthermore, 37% had access to skilled birth attendants in health facilities known as institutional delivery (ID), which is attributed to inadequate health care facilities, transportation difficulties and geographical barriers. In Myanmar, there are still disparities in accessing ID services, with 39% of women in rural areas and 77% of women in urban areas using health facilities for childbirth. This highlights the need for actions to improve access in regions that have limited resources.9,10\n\nThe 1994 Cairo International Conference on Population and Development (ICPD) emphasized the importance of male involvement (MI) in reproductive health and gender equality.11 In 2015, the recommendation from WHO emphasized the importance of men supporting women’s well-being throughout the stages of pregnancy, childbirth and postpartum.12 This definition, which is endorsed by UNFPA13 and used in this manuscript, considers both “males” and “men” as terms. Over time, studies have consistently shown that involving men in MH initiatives leads to improved MHC, increased awareness about MH issues, and better communication and support among couples, all of which benefit families and communities.14–18\n\nWhile the previous 2011-2016 five-year national health plan overlooked MI in MH, there has been a notable shift in the 2017-2021 plan by recognizing the role of men in promoting MH and advancing gender equality in Myanmar. The Ministry of Health in Myanmar has identified MI as a strategy for improving MH outcomes, and it has been explicitly incorporated into the national health policy.19\n\nDespite extensive searches on Medscape, PubMed, Google Scholar, and ProQuest with keywords “male/men/husband involvement” “maternal health care” “Myanmar”, limited research explores MI in MHC in Myanmar. Existing studies have mainly relied on quantitative, observational, community-based approaches to describe men’s knowledge and perceptions of pregnant women and their involvement in MHC practices.20–22 Moreover, these studies carried out only the quantitative approaches without incorporating mixed-method designs or interventions for exploring ID. Therefore, the objective of this study is to explore the effectiveness, acceptability, and feasibility of the men in maternity health (MiM) intervention on MI in MHC, including its impact on knowledge about MH-related issues, attitudes towards MHC and birth preparedness and complication readiness (BPCR) practices and improving ID rates through a mixed-method approach. Achieving this objective in the patriarchal context of Myanmar would be highly valuable to provide an evidence-based model for increasing ID and improving MH outcomes.\n\n\nMethods\n\nA quantitative-qualitative sequential, explanatory mixed-methods study was conducted. The quantitative methods involved pre- and post-interventional surveys, while the qualitative methods included focus group discussions (FGDs) with MH service users and in-depth interviews (IDIs) with manager-level and field-level MH service providers.\n\nThis study was implemented in Naypyitaw territory, where ID was 35.8% in 2014.9 Naypyitaw encompasses two districts, each comprising four townships. Lewe Township from Dekkhina district was purposively selected for its high population density and middle socio-economic status as the intervention group. Takkone Township from Ottara district, with a comparable population density and socioeconomic status, served as the control group.\n\nStudy population, sample size and participants selection\n\nThis study included men aged 18 years or older with primigravida female partners who were at least 16 weeks pregnant at the time of the intervention, residing in the study areas, and providing consent. In each intervention and control township, five health centres serving a high number of pregnant women were purposively selected. Midwives from these centres provided a list of eligible men whose female partners were pregnant. Using systematic random sampling, a total of 198 men (99 in each group) were selected to achieve the required sample size. Sample size calculations followed the two independent proportion formula, adapted from a study in Ethiopia, a low-income country comparable to Myanmar in terms of MMR and MHC provision.23\n\nMen in Maternity Health (MiM) Intervention\n\nThe six-month MiM education program focused on MH education for male partners of pregnant women in the intervention area. Topics included pregnancy and its complications, obstetric danger signs, the importance of MHC, including ANC, delivery care, and postnatal care, the benefits of BPCR, and safe delivery. Invitation letters were sent to male partners by public health supervisors at the health centres every first and third week to encourage participation in the MiM program’s activities. Two-hour-long education and discussion sessions occurred in five selected health centres every second and fourth week on Sundays, respectively, considering participants’ work schedules. Assigned midwives offered face-to-face health education using flip charts, distributed pamphlets, and organized group discussions, following the guidelines in the “Standardized Health Messages Handbook”.5 During discussions, male partners were encouraged to share their experiences, knowledge, and intentions regarding the adoption of new MHC-related behaviours, including topics covered in education sessions. Prior to implementation, providers were trained to deliver the MiM program’s education curriculum and guidelines. Attendance consistently remained high at 80% of participants every month, with home visits for absentees to provide health education.\n\nA quantitative survey, employing structured questionnaires, was conducted in a private room at the health centre both before and after the intervention and childbirth. The pre-intervention assessment took place from December 2018 to January 2019, and the post-intervention assessment from July to August 2019. The questionnaire was initially prepared in English, adapting Johns Hopkins Program for International Education in Gynecology and Obstetrics (JHPIEGO)’s monitoring BPCR tools,24 which had been tested for validity in low-income settings similar to Myanmar. The questionnaire was then translated into Burmese and back-translated into English. Ten village health volunteers, all holding bachelor’s degrees, were trained as interviewers for data collection. The researcher validated reported ID by cross-referencing birth certificate records and obtaining information from assigned area midwives. Quantitative data collection lasted approximately 45 minutes. Pilot testing of questionnaires was conducted in a socio-economically and geographically similar township, strategically distant to avoid cross-contamination with study townships.\n\nThe Excel database developed by the researcher was used for quantitative data entry. Descriptive statistics, including frequency, percentage, mean, standard deviation, minimum, and maximum, were used for numerical variables. For categorical variables, frequency and percentage were employed. To evaluate group homogeneity, inferential statistics included paired t-tests for within-group analysis, independent t-tests for between-group comparisons, and chi-square tests for categorical data. For the practices of MI in BPCR, five key elements: preparing the health facility for birth, ensuring the presence of skilled birth attendants, arranging transportation for delivery or emergencies, identifying potential blood donors and saving money for delivery expenses, were considered. The scores ranged from 1 (‘Yes’) to 0 (‘No’) on a scale of 0 to 5. The Statistical Package for the Social Sciences (SPSS) version 28 (IBM Corp., Armonk, NY, USA) was used for analyzing the quantitative data.\n\nThe FGDs and IDIs were conducted in the intervention township to gain a comprehensive understanding of the impact of the MiM program, exploring how acceptable and feasible the program is for preventing maternal emergencies and promoting IDs.\n\nTo ensure privacy and confidentiality, FGDs were organized in private rooms. Employing extreme case sampling, couples were chosen based on MI scores in BPCR practices related to maternal emergencies and their female partners’ ID status. Similarly, couples were selected where male partners had the lowest MI scores and their partners did not possess IDs. A total of eight FGDs were conducted separately; four sessions for male partners and four for their female partners, aiming to recruit 6-8 participants for each session.\n\nSimultaneously, IDIs were carried out with participants involved in the MiM program, including MH program managers (Township Medical Officers and Health Assistants) overseeing its implementation and MH providers (Lady Health Visitors, or Midwives). Participants included in IDIs were purposively chosen based on their roles in the MiM program, resulting in a total of 11 MH program stakeholders from the intervention township. Pilot testing of IDI and FGD guidelines was also conducted within the same township as the quantitative pilot testing. On average, IDIs and FGDs lasted around 60 and 90 minutes, respectively.\n\nFor the qualitative component, IDIs and FGDs were audio-recorded, transcribed verbatim, and analyzed thematically using the framework method. This analysis employed a combination of inductive and deductive techniques. Descriptive and analytical coding was applied to the transcripts to identify overarching themes and sub-themes, which are presented in the study findings. Qualitative data analysis were performed using NVivo version 12.\n\nThis study protocol was approved by the Ethics Review Committee on Medical Research Involving Human Subjects, Department of Medical Research, Ministry of Health, Yangon, Myanmar (Approval No: ERC/DMR/2018/133) on 5th October 2018. Before data collection, participants provided written informed consent, with confidentiality maintained throughout all stages of data collection, management, analysis, and reporting. This study was retrospectively registered with ClinicalTrials.gov on June 11, 2024 (NCT06451653), due to an initial oversight regarding the necessity of prior registration, which was corrected upon recognizing of its importance for transparency and adherence to guidelines.\n\nThe study was conducted in Naypyitaw, Myanmar, with most of the authors being Myanmar nationals. According to Myanmar’s regulations, research conducted within the country should receive ethical approval from an authorized local IRB. Consequently, we obtained approval from the Ethics Review Committee on Medical Research Involving Human Subjects, Department of Medical Research, Ministry of Health, Yangon, Myanmar. This committee, like the IRBs at the authors’ affiliated institutions, adheres to the Declaration of Helsinki. Choosing a local IRB ensured compliance with local ethical standards, streamlined the approval process, and ensured adherence to local regulations and guidelines. Additionally, while the first author is an academic researcher at Chulalongkorn University, the study’s location and context necessitated adherence Myanmar’s ethical procedures.\n\n\nResults\n\nParticipants’ socio-demographic characteristics were equated for valid comparison of the intervention’s effects between the intervention and control groups. In the intervention group, male partners’ mean age was 29.64±5.68 years, while in the control group, it was 30.44±6.09 years. Both groups had similar educational levels, manual occupations, monogamous marriages, and living arrangements. While assessing economic status using the national quintile of wealth index, the majority of participants were in the highest (39.4%) and fourth (39.9%) levels. No significant differences were found between the groups (p>0.05), ensuring the validity of comparing the intervention effects at both time points (Table 1).\n\na p-value by Pearson’s Chi-square test; Degree of freedom for Chi-square test=1.\n\nThe impact of MiM intervention on knowledge and attitudes was evaluated by mean scores comparison between intervention and control groups (Table 2). Before the intervention, there was no difference in MH knowledge between the groups (p=0.987). However, after the intervention, a notable difference emerged (p=0.001), with the intervention group scoring (39.2±10.9) compared to the control group (31.4±13.6). Similarly, attitude scores showed no statistically significant pre-interventional difference (p=0.664) but a significant post-intervention difference (p=0.044). The intervention group presented higher attitude scores (38.4±4.7) at post-intervention, while the control group’s scores remained consistent (36.5±4.0). Within-group analyses demonstrated significant improvements in knowledge and attitudes towards MH following the MiM in the intervention group (p<0.001). Additionally, the control group also experienced a significant increase in knowledge scores post-intervention compared to pre-intervention assessment (p<0.001).\n\n* Significance at p-value<0.05.\n\n** Significance at p-value<0.001.\n\nThe IDI interviews with health providers revealed that male partners initially lacked awareness regarding their role in supporting pregnancy and childbirth. However, through the influence of MiM program activities, male partners’ knowledge, attitudes, and support improved significantly, leading to increased utilization of MH services—particularly through active involvement during ANC visits.\n\n“Prior to implementing MiM, many women faced lack of support from their male partners when accessing maternal health services. The MiM encouraged male partners to accompany their wives during ANC visits, and this enhanced the utilization of maternal care services in health facilities.” (Manager-level health provider, IDI)\n\nMoreover, the FGD revealed a change in the attitude of male partners towards their roles in pregnancy and childbirth.\n\n“Prior to participating in MiM, my husband had limited awareness of his role in pregnancy and childbirth beyond providing financial support. I also held the same perspective.” (Female partner, female FGD)\n\n“I experienced swelling in my legs and high blood pressure when pregnant, he accompanied me to ANC visits, reminded me about danger signs, prepared for emergencies, and even helped with household chores that he had never done before.” (Female partner, female FGD)\n\nThe study assessed the effects of 6-month MiM intervention on MI in five key BPCR practices. Before the intervention, there were no significant differences between the two groups. However, after the intervention, a significant difference was observed between the intervention and control groups (p<0.05). The within group analysis revealed an increase in BPCR practices among participants receiving the MiM intervention (p<0.05). Male partners in the control group were more likely to secure skilled birth attendants during post-assessment, compared to pre-intervention assessment (p=0.019) (Table 3).\n\n* Significance at p-value<0.05.\n\n** Significance at p-value<0.001.\n\nBoth managers and field-level health providers recognized that a higher proportion of couples in the intervention group made childbirth plans according to BPCR guidelines, leading to safer deliveries and fewer maternal emergencies. During FGDs with male partners, it was evident that they actively participated in ensuring safe childbirth; however, their level of engagement varied depending on factors such as occupation, family size, and risk perceptions.\n\n“My occupation as a manual worker, living with my parents, and insufficient daily wages due to my large-sized family challenged me to save money for delivery and related costs.” (Male partner, male FGD)\n\n“I didn’t arrange a potential blood donor while my wife was pregnant because I didn’t expect any health issues to arise, given her overall good health throughout the pregnancy.” (Male partner, male FGD)\n\nThe study assessed the impact of MiM on ID rates, revealing that intervention group had a higher prevalence (64.6%) compared to the control group (39.4%), and this difference was statistically significant (p<0.001) (Table 4).\n\n** Significance at p-value<0.001.\n\nA manager-level health provider reported that a considerable proportion of women in the intervention group from rural areas favored home deliveries despite increased MH service utilization.\n\n“Although there was an increase in ANC utilization and a doubling of institutional delivery rates in the intervention township, about one-third of rural women still opt for home delivery due to the distance from health facilities.” (Manager-level health provider, IDI)\n\nWhile most women had experiences with their male partners in BPCR activities, some encountered challenges such as cultural influences that favored home delivery and financial constraints.\n\n“I chose home delivery with my mother and a traditional birth attendant, so it eliminated the need for my husband to arrange transportation to a delivery facility.” (Female partner, female FGD)\n\n“Despite my husband’s advice for hospital delivery, I chose home delivery due to strong encouragement from my mother and aunt, who had personal experience with it.” (Female partner, female FGD)\n\nThe acceptability and feasibility of the MiM program were assessed exclusively through qualitative interviews. Health providers highlighted the positive response from participants towards the MiM as male partners expressed an understanding of MH and recognized their role in ensuring safe delivery.\n\n“At first, some men resisted attending the sessions because they felt that maternal health was not their responsibility and were unfamiliar with the program. However, educational efforts helped them realize their importance leading to increased attendance in the MiM program over time.” (Field-level health provider, IDI)\n\nFGDs with male partners revealed that they gained more confidence in supporting their female partners during pregnancy and became more willing to engage in discussions. Women preferred the program due to its positive impact on their partners’ knowledge and behavior, particularly including healthy pregnancy outcomes through nutrition.\n\n“I first hesitated to ask questions but later on gained confidence and took part in the activities as facilitators created an enabling environment and assured us (male partners) that no question was basic or silly during the sessions.” (Male partner, male FGD)\n\n“After the MiM program, my husband learned about the necessity of balanced nutrition during pregnancy. Consequently, he ensured my balanced diet and regular intake of iron and folic acid supplements, which led to the birth of our baby without any complications.” (Female partner, female FGD)\n\nThe program enabled male partners to engage with MHC providers, addressing concerns and providing tailored materials for specific MH needs.\n\n“Male partners gained new skills in birth preparedness, including knowledge about arranging blood donors in case of emergency situations. In our community, where health literacy is low, many people are unaware of their blood group.” (Field-level health provider, IDI)\n\nBoth men and their partners recognized the impact of the program on their roles and improved MH outcomes by promoting the identification of issues and preventing complications.\n\n“When I experienced vaginal bleeding, my husband arranged me to go for regular check-ups and accompanied me to the hospital. It was revealed that the placenta had implanted at the bottom of my uterus. Because of his support, the condition was detected early, and I received timely medical intervention to avoid a potential emergency.” (Female partner, female FGD)\n\nTechnical feasibility\n\nManager-level health providers emphasized the feasibility of MiM in terms of its technical aspects, specifically mentioning its design and ease of comprehension for male partners who have limited literacy skills.\n\n“MiM’s educational tools are designed for easy understanding by the intended audience, especially those with limited literacy or health knowledge. The tools are user-friendly for facilitators during MiM sessions, aligning well with community standards. The use of visual aids addresses the challenges and concerns that men face during their wives’ pregnancies, providing valuable support tailored to meet the needs of the community.” (Manager-level health provider, IDI)\n\nMen and their partners found the health education materials, particularly the visuals, easily comprehensible, effectively conveying essential information on MH and emergency preparedness.\n\n“Although I can’t read as proficiently as others, I can still understand the information by looking at the visual aids and listening to the health education provided by the midwife.” (Male partner, male FGD)\n\n“I observe the pictures in the books and pamphlets provided by the MiM to explain the necessary actions related to maternal health and preparedness for emergencies to my husband. This also makes it easier for me to grasp what needs to be done.” (Female partner, female FGD)\n\nTime feasibility\n\nRegarding the schedule of MiM, health providers emphasized the need for flexibility to accommodate the time constraints of male partners. Additionally, most men expressed their preference for weekend sessions and convenient locations, while some suggested shorter and more focused session durations to enhance engagement.\n\n“Some sessions were long, which made it difficult for us (male partners) to maintain focus and engagement throughout. If these sessions were divided into shorter and more manageable parts, it could improve our overall learning experience.” (Male partner, male FGD)\n\nIDIs with health providers recommended a suitable program duration of six months for the male partners to acquire new skills. In FGDs, some men found that a six-month program duration was adequate for learning while others suggested it should be shorter due to their early knowledge acquisition.\n\n“I think six-month program is too long. I gained the knowledge and skills needed within the first few months. With the varied needs of different individuals, some taking longer times, a shorter program for others within this duration should be considered.” (Male partner, male FGD)\n\nOperational feasibility\n\nManager-level health providers addressed the challenges by engaging with the community and closely monitoring the process of the program. Field-level providers acknowledged that the implementation of MiM program has shown feasibility and positive outcomes. However, both emphasized the need for additional trained personnel with skills in engaging male partners to ensure the successful implementation of MiM.\n\n“The MiM yielded positive outcomes with an increase in institutional deliveries and maternal health practices. However, for program sustainability, trained personnel are needed to consider as we have our existing duties and limited staff resources.” (Manager-level health provider, IDI)\n\nEconomic feasibility\n\nBoth manager- and field-level providers highlighted that one of the advantages of MiM is its feasibility, as it is offered free of charge, which encourages active participation. During FGDs with male partners, it was observed that they expressed favorable views regarding affordability but mentioned concerns about transportation costs and potential loss of daily income for those engaged in manual labor. Similarly, women acknowledged its affordability; however, one participant expressed concerns about her husband’s work absence during MiM sessions.\n\n“Transportation costs are required to attend the MiM sessions. Unlike others, as a manual worker, I lost my daily income while participating in the MiM education sessions.” (Male partner, male FGD)\n\n“As my husband is the breadwinner in our family, he faced work challenges due to attending MiM education sessions since we depend on his income. Fortunately, we were able to resolve this by consulting with his employer, who let him attend during his break time and make up for the work he missed at another time.” (Female partner, female FGD)\n\n\nDiscussion\n\nThis study was carried out as part of the Maternal and Reproductive Health program in Myanmar to explore the effectiveness of MiM programme on MI with regard to improving MHC and its impact on ID. This study employed a mixed-methods approach, including quantitative surveys and qualitative interviews, and ultimately found significant increases in knowledge, attitudes, and BPCR practices among male partners in the intervention compared to the control group.\n\nThe MiM program aimed to address gaps in MH in Myanmar, where ID rates are not optimal. By providing targeted education and facilitating interactive discussions, MiM effectively addressed the initial lack of knowledge and limited awareness among male partners about their role in supporting pregnancy and childbirth. The intervention significantly changed the male partners’ attitudes towards their involvement in pregnancy and childbirth. These findings are consistent with evidence from an interventional quasi-experimental study conducted in Tanzania that involved men with pregnant partners, as well as another study in Nigeria that employed a stepped-wedge cluster randomized controlled trial involving spouses of pregnant women. Both studies showed improvements in knowledge and attitudes among male partners regarding MH following the intervention.25,26 Interestingly, in this study, the post-intervention knowledge score unexpectedly increased in the control group due to MH education received from various sources, including neighbors, local MHC providers, and mass media. Since 2014, MH education programs have been disseminated through radio and TV series, as well as mobile applications like ‘May May’ and ‘Phay Phay’.27\n\nAccording to the White Ribbon Alliance and JHPIEGO, it is more effective to prevent maternal emergencies rather than just managing them after they occur. It is crucial to adhere to BPCR practices to avoid negative consequences, particularly concerning birth plans.24,28 In this study, the MiM intervention significantly improved BPCR practices among male partners. In contrast, a quasi-experimental intervention study involving married men in Nigeria presented low MI in BPCR practice possibly due to religious misconceptions.29 However, a randomized controlled intervention study conducted in Gambia, focusing on spouses of pregnant women, reported an increase in BPCR practices,30 which aligns with the findings of the MiM intervention. These findings highlight the importance of targeted interventions like the MiM program in improving MI in MHC and ultimately contributing to better MH outcomes. Furthermore, in this study, male partners in the control group showed an increase in planning for skilled birth attendants during the post-assessment, possibly because even when their wives chose home delivery, they needed to arrange for a traditional birth attendant.\n\nPrevious randomized controlled intervention studies conducted in Nepal and Gambia have highlighted the impact of involving male partners in MHC. These studies have shown that when men actively support their wives during pregnancy and childbirth, it leads to improved MH outcomes and increased utilization of MH utilization.30,31 This MiM study supports those findings by demonstrating an increase in ID among intervention group compared to the control group. The intervention effectively empowered male partners to play an active role, which positively influenced women’s decisions to opt for ID. However, despite the success of the intervention, a considerable number of women in both groups still choose home deliveries. This suggests that cultural influences and financial constraints continue to impact the uptake of ID services. These findings are consistent with qualitative research conducted in Ghana and Uganda that also emphasized how sociocultural norms and practices influence delivery decisions. This underscores the need for targeted interventions aimed at promoting IDs.32,33\n\nThe qualitative data provided insights into the acceptability and feasibility of MiM program. Both male and female participants expressed responses emphasizing its effectiveness in improving learning, communication, and MH outcomes. The assessment of feasibility demonstrated that the program is technically and operationally viable with participants giving feedback on its design of visual aids and accessibility of health education materials. However, health stakeholders highlighted the need for trained personnel due to challenges in human resources. These findings emphasize the importance of providing training and support to health care providers for the successful implementation of the program, aligning with realist reviews and discussion studies on MI in low- and middle-income countries.34,35 Flexible scheduling played a role in accommodating time constraints and competing demands for male partners thereby enhancing operational feasibility. While participants viewed the feasibility of MiM positively since it is a free program, concerns were raised about transportation costs and income loss for male partners. This highlights the importance of addressing financial constraints to enhance MI, which aligns with similar findings, from mixed-method studies conducted in Kenya and a qualitative study in Malawi.36,37\n\nOverall, this present study provides important new insights into how and why the MiM intervention is useful in promoting MI in MH and increasing ID rates in Myanmar, thereby showing evidence-based programs to improve MH outcomes. The results show that partner-targeted interventions can be effective with a positive change in terms of knowledge, attitudes, and practices regarding MHC. Similarly, planned interventions targeting other areas and populations of the country could be helpful in advancing MH outcomes. However, challenges such as cultural influences, financial constraints as well as trained personnel need to feature in future implementations so that the intervention has an optimized effect. The effectiveness of the MiM program may vary across diverse settings, requiring suitable approaches to address particular MI challenges that exist in MHC setting.\n\nThis study employs a quantitative-qualitative sequential explanatory mixed-methods approach with methodological rigor, integrating pre- and post-intervention surveys with IDIs and FGDs. It represent the first intervention study with male partners to improve knowledge, attitudes, and BPCR practices for safe motherhood and ID in Nay Pyi Taw. The MiM intervention’s tailored focus on male partners addresses community-specific needs, resulting in increased ID rates through health education and discussion. Additionally, the use of systematic random sampling ensures the reduction of selection bias, while comprehensive training for data collectors is designed to minimize bias. These strengths enhance the credibility and validity of the findings, providing valuable insights into the MiM’s effectiveness in improving MH outcomes.\n\nDespite its strengths, this study was conducted in two purposively chosen townships in Nay Pyi Taw Union Territory, thus limiting generalizability within Myanmar or beyond. The six-month intervention may have limited the assessment of long-term MiM impact, and this would justify a longer follow-up to understand changes over time. External co-interventions, such as mass media and information from nearby health providers, could influence the outcomes of the study. About 20% of the participants missed monthly MiM activities at health centres, which hampered collective learning through group discussions and overall intervention effectiveness, despite efforts to provide MiM face-to-face education at home. Future MI-focused interventions in MHC should, therefore, address such limitations for stronger impact and applicability in similar settings.\n\n\nConclusions and recommendation\n\nThis study provides compelling evidence that MiM program markedly improved male partners’ knowledge, attitudes, and practices concerning MH in Myanmar, leading to a noticeable increase in ID prevalence. The findings highlight the critical role of men in MHC in creating an enabling environment for safe deliveries and improved MH outcomes. Continuation of the health education sessions through well-trained field-level health staff is strongly recommended, subject to receiving adequate support for specific MI guidelines and budget for training health staff from the central-level Ministry of Health. It is also suggested to establish community support groups involving male and female members as interactive platforms to strengthen MI’s advantages in MHC. This would extend such initiatives to different settings and populations, contributing to a broader MH promotion. Lastly, further research, including longitudinal studies to reveal insights into MiM program’s long-term impact, along with qualitative studies focusing on male and female points of view with health care providers, is recommended to reveal barriers and facilitators towards continued MI in MHC and to refine interventions for promoting MI in the future.",
"appendix": "Data availability statement\n\nQualitative data cannot be made publicly available according to the Ethics Review Committee on Medical Research Involving Human Subjects, Department of Medical Research, Ministry of Health, Yangon, Myanmar because the datasets generated and/or analysed during the current study comprise collected data from specific districts and townships in Naypyitaw, Myanmar, and the information may be identifiable to particular individuals, risking a breach in confidentiality.\n\nQualitative data (limited de-identified transcripts of interviews) can be requested by contacting to the first author, May Chan Oo (maechanoo@gmail.com) under no strict conditions. Please note that access to these transcripts is subject to limitations related to participant privacy and data sensitivity, and are available only in Burmese language.\n\nFigshare: Effectiveness of men in maternity health (MiM) intervention on male involvement in maternal health care to improve maternal health outcomes in Naypyitaw, Myanmar. https://doi.org/10.6084/m9.figshare.25039013.\n\nThis project contains the following underlying data:\n\n- Quantitative data\n\nFigshare: Supplementary materials for the “effectiveness of men in maternity health (MiM) intervention on male involvement in maternal health care to improve maternal health outcomes in Naypyitaw, Myanmar” are available in https://doi.org/10.6084/m9.figshare.25039013.\n\nThis project contains the following extended data:\n\n- Information sheet and informed consent forms\n\n- Survey questionnaire\n\n- Interview and focus group discussion guides\n\nFigshare: COREQ and TREND checklists for Effectiveness of men in maternity health (MiM) intervention on male involvement in maternal health care to improve maternal health outcomes in Naypyitaw, Myanmar. in https://doi.org/10.6084/m9.figshare.25039013.\n\nAll data 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 express our sincere gratitude to all study participants, including male and female partners, and health stakeholders, for their valuable insights that shaped this research. Our appreciation also goes to the health authorities in Naypyitaw, Myanmar, for their support and cooperation throughout the study.\n\n\nReferences\n\nUnited Nations. Sustainable Development Goals: 2015. [cited 2023 Sep 3]. Reference Source\n\nUnited Nations Population Fund: Annual Report 2017. New York: 2018.\n\nWorld Health Organization: Maternal mortality.2018. [cited 2023 Sep 3]. Reference Source\n\nCenters for Disease Control and Prevention: Maternal and Infant Health.2021. [cited 2023 Sep 3]. Reference Source\n\nMinistry of Health and Sports (MoHS), World Health Organization, Unicef: Standardized Health Messages. 1st ed.Myanmar: 2017.\n\nWorld Health Organization: Trends in maternal mortality 2000 to 2020: estimates. WHO, UNICEF, UNFPA, editor. Geneva, Switzerland: World Bank Group and UNDESA/Population Division; 2023.\n\nKassebaum NJ, Bertozzi-Villa A, Coggeshall MS, et al.: Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 384(9947): 980–1004. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUnited Nations Population Fund: State of the world population 2019: Unfinished business - the pursuit of rights and choices for all. New York: 2019.\n\nMinistry of Health and Sports (MoHS) and ICF: Myanmar Demographic and Health Survey 2015-16. Nay Pyi Taw, Myanmar, and Rockville, Maryland USA: 2017.\n\nHtun NMM, Hnin ZL, Khaing W: Empowerment and health care access barriers among currently married women in Myanmar. BMC Public Health. 2021; 21(1): 139. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUnited Nations Population Fund: Programme of Action of the International Conference on Population and Development. Cairo: 1994 5-13 September 1994.\n\nWorld Health Organization: 2015; WHO recommendations on health promotion interventions for maternal and newborn health 2015. Geneva, Switzerland.\n\nUnited Nations Population Fund: Male Involvement in Sexual and Reproductive Health [press release]. Ghana: UNFPA, Ghana Country Office 5th Country program (CP5) 2006-2011; 2006.\n\nYargawa J, Leonardi-Bee J: Male involvement and maternal health outcomes: systematic review and meta-analysis. J. Epidemiol. Community Health. 2015; 69(6): 604–612. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDavis J, Vyankandondera J, Luchters S, et al.: Male involvement in reproductive, maternal and child health: a qualitative study of policymaker and practitioner perspectives in the Pacific. Reprod. Health. 2016; 13(1): 81. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTokhi M, Comrie-Thomson L, Davis J, et al.: Involving men to improve maternal and newborn health: A systematic review of the effectiveness of interventions. PLoS One. 2018; 13(1): e0191620. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBagenda F, Batwala V, Orach CG, et al.: Benefits of and Barriers to Male Involvement in Maternal Health Care in Ibanda District, Southwestern, Uganda. Open J. Prev. Med. 2021; 11: 411–424. Publisher Full Text\n\nSharma S, Kc B, Khatri A: Factors influencing male participation in reproductive health: a qualitative study. J. Multidiscip. Healthc. 2018; 11: 601–608. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMinistry of Health and Sports (MoHS): Myanmar National Health Plan 2017-2021. Nay Pyi Taw, Myanmar: 2016.\n\nAmpt F, Mon MM, Than KK, et al.: Correlates of male involvement in maternal and newborn health: a cross-sectional study of men in a peri-urban region of Myanmar. BMC Pregnancy Childbirth. 2015; 15(1): 122. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWai KM, Shibanuma A, Oo NN, et al.: Are Husbands Involving in Their Spouses’ Utilization of Maternal Care Services?: A Cross-Sectional Study in Yangon, Myanmar. PLoS One. 2015; 10(12): e0144135. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMyint ZMM, Lapvongwatana P, Chansatitporn N, et al.: Involvement in practising family planning among married men in Kyaukpadaung Township, Mandalay Region, Myanmar. J Public Hlth Dev. 2021; 19(2): 240–251.\n\nDemissie DB: Involvement of Male in Antenatal Care, Birth Preparedness and Complication Readinessand Associated Factors in Ambo Town, Ethiopia. J. Health, Med. Nursing. 2016; 27: 14–23.\n\nJHPIEGO: Monitoring Birth Preparedness and Complication Readiness tools and indicators for maternal and newborn health. Maryland, USA: 2004.\n\nAugust F, Pembe AB, Mpembeni R, et al.: Community health workers can improve male involvement in maternal health: evidence from rural Tanzania. Glob. Health Action. 2016; 9: 30064. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCockcroft A, Omer K, Gidado Y, et al.: Universal home visits improve male knowledge and attitudes about maternal and child health in Bauchi State, Nigeria: Secondary outcome analysis of a stepped wedge cluster randomised controlled trial. J. Glob. Health. 2022; 12: 04003. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBarrie G: Case study Ooredoo Myanmar: Myanmar, Mobile and Maternal Health. Myanmar: 2015.\n\nThe White Ribbon Alliance for Safe Motherhood: Saving Mothers’ Lives, What Works: A Field Guide for Implementing Best Practices in Safe Motherhood. India: 2002.\n\nIbrahim M, Sufiyan MA, Idris S, et al.: Effect of a behavioral intervention on male involvement in birth preparedness in a rural community in Northern Nigerian. Ann. Niger. Med. 2014; 8: 20–27. Publisher Full Text\n\nTunkara- Bah H, Adeyemo FO, Okonofua FE: Effects of health education on spousal knowledge and participation in birth preparedness in Farafenni Regional Hospital, The Gambia: a randomized trial. BMC Pregnancy Childbirth. 2021; 21(1): 129. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMullany BC, Becker S, Hindin MJ: The impact of including husbands in antenatal health education services on maternal health practices in urban Nepal: results from a randomized controlled trial. Health Educ. Res. 2007; 22(2): 166–176. PubMed Abstract\n\nGanle JK, Dery I: ‘What men don’t know can hurt women’s health’: a qualitative study of the barriers to and opportunities for men’s involvement in maternal healthcare in Ghana. Reprod. Health. 2015; 12: 93. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGopal P, Fisher D, Seruwagi G, et al.: Male involvement in reproductive, maternal, newborn, and child health: evaluating gaps between policy and practice in Uganda. Reprod. Health. 2020; 17(1): 114. PubMed Abstract | Publisher Full Text | Free Full Text\n\nClark J, Sweet L, Nyoni S, et al.: Improving male involvement in antenatal care in low and middle-income countries to prevent mother to child transmission of HIV: A realist review. PLoS One. 2020; 15(10): e0240087. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDaniele MAS: Male partner participation in maternity care and social support for childbearing women: a discussion paper. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 1827; 376(376): 20200021. Publisher Full Text\n\nOngolly FK, Bukachi SA: Barriers to men’s involvement in antenatal and postnatal care in Butula, western Kenya. Afr. J. Prim. Health Care Fam. Med. 2019; 11(1): e1–e7. PubMed Abstract | Publisher Full Text\n\nSakala D, Kumwenda MK, Conserve DF, et al.: Socio-cultural and economic barriers, and facilitators influencing men’s involvement in antenatal care including HIV testing: a qualitative study from urban Blantyre, Malawi. BMC Public Health. 2021; 21(1): 60. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "350077",
"date": "26 Dec 2024",
"name": "Ramesh Kumar",
"expertise": [
"Reviewer Expertise Related to public 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 study evaluates the \"Men in Maternity\" (MiM) intervention in Naypyitaw, Myanmar, to improve male involvement in maternal health care (MHC). Using a mixed-methods approach, the intervention significantly enhanced male partners' knowledge, attitudes, and practices, leading to higher institutional delivery (ID) rates. Challenges included cultural barriers, financial constraints, and personnel shortages. Strengths\nInnovative Intervention: This paper effectively addresses a key gap by involving men, a novel approach for improving MHC outcomes in Myanmar. Robust Design: The mixed-methods approach ensures a comprehensive evaluation of the intervention’s effectiveness, acceptability, and feasibility. Mixed Methods: Significant improvements in knowledge and ID rates were complemented by qualitative findings that highlighted cultural shifts and positive stakeholder feedback. Policy Implications: The study provides evidence-based recommendations that are adaptable to other low-resource settings\nWeaknesses\nLimitations: Financial constraints, cultural barriers, and limited trained personnel may hinder large-scale implementation. Time constrains: The 6-month duration may not capture long-term sustainability or the full impact of the MiM program. Generalizability: Findings are specific to Naypyitaw and may not represent other regions in Myanmar with different socio-cultural contexts.\nThis is an excellent paper; however, please include the study design in the methods section, provide a reference for the tool used, mention the ethical approvals or consent procedures (written/informed), outline the implications for practice, specify the outcome measures, and detail the tests performed in 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?\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": "350079",
"date": "06 Jan 2025",
"name": "Lafi Munira",
"expertise": [
"Reviewer Expertise Health behavior",
"behavioral change",
"mixed methods",
"experimental study",
"qualitative study."
],
"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\n1) Introduction: Could you please include similar intervention studies on men's involvement from other countries or neighboring regions with similar patriarchal cultures, if available?\n2) Method: Please add 1–2 sentences explaining the reasons for choosing a sequential explanatory mixed-methods design, supported by references. For example: 'This design was chosen to first quantitatively examine the phenomena of interest and subsequently provide in-depth qualitative insights to contextualize and explain the quantitative findings (Creswell & Plano Clark, 2018).\n3) Method - Measurement Tools:For the quantitative section, could you please elaborate on the measurement tools used, including a detailed description of the dependent and independent variables? Additionally, specify the cut-off points for each measurement where applicable.\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/13-939
|
https://f1000research.com/articles/13-168/v1
|
08 Mar 24
|
{
"type": "Research Article",
"title": "A survey of water chemistry used in zebrafish facilities and their effects on early zebrafish development",
"authors": [
"Cosima S. Porteus",
"Ella Waples",
"Anna Dempsey",
"Gregory Paull",
"Rod W. Wilson",
"Ella Waples",
"Anna Dempsey",
"Gregory Paull"
],
"abstract": "Background There are a variety of published standard methods and water chemistry recommendations for zebrafish (Danio rerio) husbandry, but empirical evidence for their justification is often lacking, as is information on some variables that have important biological effects on fish. Importantly, these different recommendations could contribute to variability in results and fish welfare between or within institutions.\n\nMethods Here we document the current range of water chemistry used by various research institutions around the world and report initial findings on their effects on the development and growth of zebrafish. Over 40 institutes responded to a survey that revealed a large variation in water chemistry used for zebrafish husbandry including differences in the set-points and acceptable ranges for temperature, pH and conductivity. In subsequent experiments, zebrafish (D. rerio, WIK) embryos/larvae exposed to a large range of salt concentrations (50μM to 10mM Na+ or 30 – 2500 μS/cm) and CO2 levels (400 – 8,000 μatm).\n\nResults Larvae exposed to the lowest salt concentration (5 μM Na+ or < 30μS/cm) had a slower response to touch and their swim bladders were not inflated. Larvae exposed to 5-100 μM Na+ were 5 % shorter in total body length than those exposed to higher salt concentrations (>100 μM Na+). Zebrafish embryo/larvae exposed to intermediate pCO2 values (~2000 μatm) were 1 to 3.5% longer than those exposed to either ambient (400 μatm) or higher (4000 μatm) pCO2, but pCO2 did not affect developmental endpoints up to 4 dpf.\n\nConclusions Overall, we highlight the magnitude of variation in water chemistry used within zebrafish research and provide some empirical evidence to show that not all of these water conditions might be optimal for developing zebrafish and reproducibility of research, although further research is necessary to determine longer-term effects of water chemistry on older larvae, juveniles and adults.",
"keywords": [
"Growth",
"development",
"zebrafish",
"water chemistry",
"pH",
"temperature",
"conductivity",
"salinity",
"polyculture"
],
"content": "Introduction\n\nFish physiologists have known for decades that ion levels have a dramatic influence on the physiology and health of fish generally, but also specifically on the ability to cope with ion and acid-base disturbances (Brauner et al., 2019). Sodium (Na+) and chloride (Cl-) are the two major ions that freshwater fish must actively take up from the water for survival. Critically, they are also the key counter-exchange ions that freshwater fish require for regulating their internal acid-base balance (i.e. for excreting excess acid or base, respectively). These are important for internal pH homeostasis which in turn is vital for ensuring all cellular proteins maintain functionality. It is well established that animals that are kept under suboptimal conditions must devote more energy to maintaining homeostasis, rather than using it for growth, gamete production and immune function (Wootton, 1999). For example, rainbow trout (Oncorhynchus mykiss) acclimated to low NaCl concentrations had double the blood acidosis after exercise and took twice as long to recover compared to fish acclimated to very high NaCl (Tang et al., 1989). Similarly, rainbow trout exposed to elevated CO2 recovered their blood pH quicker and more completely when either NaCl, or Ca2+, or HCO3- were higher (Iwama and Heisler, 1991; Larsen and Jensen, 1997). Importantly, fish maintained at the lower ion levels in these same studies were often incapable of restoring blood pH at all, and the ranges tested (approximately 0.05 to 5 mM) encompass the range typically found in natural freshwater environments, and in zebrafish facilities.\n\nThe success of the zebrafish as a model species is not surprising given their high fecundity, transparent embryos, short life cycle as well as their natural distribution within the floodplains of the Ganges and Brahmaputra Rivers, which vary greatly in water chemistry (Lee et al., 2020). This natural history accounts for much of the tolerance of zebrafish to a wide range of physiological stressors. However, despite the ability of zebrafish to survive wide-ranging water chemistry parameters, certain conditions may not be optimal for thriving. Currently, around 87% of zebrafish used for scientific research are kept in recirculating systems (Lawrence, 2007; Lidster et al., 2017). CO2 can accumulate in these systems unless significant CO2-stripping effort is employed to remove it, i.e. more than just sufficient aeration to restore normal oxygen levels (Hu et al., 2011; Summerfelt et al., 2000). This is due to CO2 having a 30 times greater solubility in water compared to O2, and also the slower reaction speed of CO2 hydration and its reversal. Therefore, it is more difficult to remove the respiratory CO2 excreted by fish than it is to replace the O2 they consume and, as a result, CO2 gradually accumulates on each pass through the system whilst normal O2 levels are maintained. It has been previously established that zebrafish can cope with high pCO2 (partial pressure of CO2) conditions, if kept in hard water with very high levels of NaCl (13 mM) and HCO3- (5 mM) (Mölich and Heisler, 2005). However, despite the ability to regulate blood acid-base balance, living in high CO2 water has further, more holistic impacts on fish performance. For example, it reduces growth and efficiency of digestion in juvenile and adult Atlantic salmon (Salmo salar; Fivelstad, 2013; Mota et al., 2020) and adult Atlantic cod (Gadus morhua; Tirsgaard et al., 2015) and reduces the conversion of yolk into growth in larval pink salmon (Oncorhynchus gorbuscha; Ou et al., 2015). Also, 12 weeks exposure to elevated CO2 in Atlantic salmon caused 72 differentially expressed genes, 60 being down-regulated with a predominance of those being associated with immune responses (Mota et al., 2020).\n\nA surprisingly wide range of water chemistry is used throughout the zebrafish community (Lawrence, 2007). For example, Na+ concentration varies more than 350-fold in various “recipes” for freshwater media established for use in raising larvae until the first feeding stage (4-5 dpf, Table 1). Moreover, these variations not only exist between facilities but even within them, with different researchers having different preferred larval media within the same institution. Variations also exist between different life stages within a research group and between animals destined for stock or experiments. By discussing this with colleagues and reading what has been reported elsewhere (Lee et al., 2022), we found that this is due to differences in standards for the particular field or due to historical use (i.e. how researchers were trained to do it). For example, the standard solution used for toxicological and pharmaceutical testing in Europe is ISO 7346-3 (ISO7346-3, 1996) which states that this solution can be diluted up to 6 times to reduce water hardness in order to minimize the effects of salts on the bioavailability and uptake of toxicant chemicals (including pharmaceuticals) being studied (Pinheiro et al., 2021). At the same time, fish destined for maintaining stock in the same facility might be raised by facility staff in media recommended in The Zebrafish Book (Westerfield, 2007). Furthermore, posts on online chat groups indicate that researchers change the original recipes of standard solutions such as E2 or E3 (Nüsslein-Volhard and Dahm, 2002), introducing even more variability and uncertainty in methods used and results. Finally, it is not clear what empirical evidence these recommended “recipes” for freshwater media are based upon regarding their impact on either fish health or research outcomes.\n\nThis clearly shows the large fold difference (between the lowest and highest ion concentrations of all media, far right column) between the main ion concentrations between these different solutions.\n\n1 OECD Test No. 236: FET, 2013.\n\n2 ISO, 1996.\n\n3 Nüsslein-Volhard and Dahm, 2002.\n\n4 Gustafson et al., 2012.\n\n5 Westerfield, 2007.\n\n6 Sawant et al., 2001.\n\nIn addition to the immediate effects of differences in water chemistry, we propose that raising zebrafish under such varied conditions can also affect their response to environmental variables in later life as previously shown in juvenile European sea bass (Dicentrarchus labrax; Fokos et al., 2017). Developmental plasticity has been shown for stressors such as temperature (Schaefer and Ryan, 2006) and hypoxia (Robertson et al., 2014) and exposure during early life to high CO2 can alter the ventilatory sensitivity of zebrafish in adulthood (Vulesevic and Perry, 2006). Therefore, early exposures to different water chemistry conditions could affect how zebrafish respond to various stressors later in life, and potentially give rise to a range of phenotypes when exposed to various stressors or toxicants as juveniles or adults. This in turn causes discrepancy between the outcomes of similar studies conducted at different institutions. Indeed, methodological issues stemming from insufficient understanding of factors that may influence experimental results has been previously identified as a factor that can contribute to the reproducibility and replicability of results in zebrafish research studies (Gerlai, 2019). In principle, poor reproducibility and replicability is likely to result in a greater total number of animals being used in research, as it may encourage the repeat of experiments to explore what the most accurate or representative outcome of research actually is.\n\nThe purpose of the current study was to gather quantitative data regarding the variation in water chemistry used by different institutions using zebrafish and to explore how this may affect the early development of zebrafish. To achieve this, we then measured standard developmental endpoints (Kimmel et al., 1995) and the growth of zebrafish under different water chemistry regimes up to the independent feeding stage. We hypothesized that the growth and development of zebrafish would be affected by changes in salt level and pCO2 and that these differences would be more pronounced in high and low salt extremes and at the highest CO2 level.\n\n\nMethods\n\nA survey to determine the water chemistry ranges used to house zebrafish was sent to the global zebrafish community (distributed to the Zebrafish Husbandry Association and the British Zebrafish Husbandry Association list servers, and other institutions on an individual basis) between February 2018 and August 2019 (University of Exeter Ethics Committee, ID 5542334). Forty institutions/zebrafish facilities in 12 countries from Europe, USA, Canada, Australia, New Zealand and Asia responded to the survey. We obtained informed consent from all the participants in writing to share these data without disclosing institutional information. The survey questions focused on identifying the target and actual operating range of water chemistries known to have effects on fish (see Supplementary Materials for the Survey). Specifically, the questionnaire requested detailed information regarding source water, salt addition (type, manufacturer and concentrations/ratios used), water filtration methods, water chemistry parameters monitored, and operating conditions for the important life stages of zebrafish development, i.e. embryo, larvae and adult. In the questionnaire, the institutions were also requested to define the age ranges for the different stages of development as this varied between institutions. Sodium is the dominant cation across global freshwater ecosystems (Pinheiro et al., 2021) as well as in most established zebrafish media. However, given that the freshwater media commonly used to culture zebrafish are synthetic combinations of many individual salts, not just those containing sodium, for simplicity throughout we refer to the different treatments in terms of their total sodium concentration. Total salt concentrations were calculated using the target conductivity (which is proportional to the sum of all ions present) or the midpoint between the reported minimum and maximum conductivity for those institutions where a target conductivity was not provided. Where minimum and maximum values were given, these refer to the point at which action would be taken at the relevant local institute to correct the water chemistry. Throughout the manuscript, system water refers to the standard water used for housing fish in each facility, but the salt concentration in these systems is typically different at each site. For example, the sodium concentration of system water in these facilities varies from 2.1 mM to 10.6 mM with most between 3.2 and 6.3 mM.\n\nWater samples were collected from three prominent zebrafish facilities in the UK. The rationale for choosing the three facilities was that they represented typical mid-to-large scale zebrafish facilities; they used commercially available tanks and recirculating filtration systems to house their fish; they were well established with standardised husbandry methods and experienced animal care staff and management; and they were well stocked with fish at densities typically reported for zebrafish facilities (4-10 fish/L) and within set guidelines (reviewed by Lee et al., 2022). All of these factors suggested that the water chemistry ranges recorded by these institutions would be a good representation of other facilities. System water was sampled from 3 to 4 different locations within each facility (10 samples in total). Water samples (12 ml) were preserved in gas-tight vials with mercuric chloride (HgCl2) according to standard methods (Dickson et al., 2007) and stored at 4°C. The samples were transported to the University of Exeter, where salinity and pHNBS were measured upon arrival using a salinity and conductivity system (YSI Model 30, YSI incorporated, Yellow Springs, Ohio, USA), pH meter (Model HI 8314, Hanna Instruments, Leighton Buzzard, UK) and pH probe (Model pHC2401, Radiometer Analytical, Lyon, France) calibrated with National Bureau of Standards (NBS) buffers. System water samples were analysed for dissolved inorganic carbon (DIC) using a custom built system (Lewis et al., 2007). Measured temperature, salinity, pH and DIC values were used to calculate average water pCO2 and total alkalinity (TA – a measure of the water’s acid-neutralizing capacity) using the CO2SYS software using the GEOSECS constants.\n\nAll experiments were carried out in the University of Exeter Aquatic Resources Centre (ARC), and procedures were approved by the Home Office (License No P88687E07).\n\nZebrafish were bred from the Wild Indian Karyotype (WIK) strain, by small group batch spawning, consisting of 4 individuals per sex. The fish were placed in the breeding tank the previous night and spawning was initiated from 08:55 with lights turning on gradually, and embryos were collected at 09:45. The standard breeding conditions at the University of Exeter are 28±1°C, using system water with an average pH of 7.5. At the time of this study, the system water was reverse osmosis (RO) reconstituted with 2.1 mM calcium chloride dihydrate (CaCl2•2H2O), 0.53 mM magnesium sulphate heptahydrate (MgSO4•7H2O), 0.39 mM sodium bicarbonate (NaHCO3), 0.08 mM potassium chloride (KCl), and 0.5 mM sodium chloride (NaCl).\n\nAll egg test procedures were carried out following the guidelines for the OCED FET Test No. 236 (OECD, 2013), using larvae at 0 to 4 days post fertilisation (dpf) as follows. Embryos were separated into groups of 24 individuals per treatment as specified in the FET assay (OECD, 2013) and transferred <90 minutes post fertilisation into group treatment conditions into a 6 well plate in the CO2 incubator, via a pipette (15 embryos per 10 ml treatment solution), during the 4 to 16 cell cleavage stage (OECD, 2013), in a 28°C environment. Fertilisation success was checked and recorded 3 to 4 hours post fertilisation (hpf) (Brannen et al., 2010). For test results to be valid a fertilisation success >70% must be achieved, in accordance with the OECD FET assay guidelines (OECD, 2013). The first twelve fertilised embryos were chosen per treatment and transferred using a 200 μl commercially available pipette with a widened tip opening into individual wells of a 12-well plates containing 1 ml of the same initial treatment solution (OECD, 2013). This resulted in each embryo being kept in 1.2 ml at 28±1°C in the respective CO2 incubator by 4 hpf. All the experiments were performed on two different batches (experimental unit) of embryos for a total sample size of 19-24 embryos per treatment, except Experiment 1, 2000 μtm at 5 μM Na+ where N=11 because this lowest salt level was omitted in the first batch of embryos used. A total of 192 total animals used for experiment 1 and 336 for experiment 2 (Supplementary tables S1 and S2). The only reason to exclude an animal from an experiment was natural mortality or a body shape score of less than 5 (mildly to severely deformed). A body shape less than 5, absence of a heart beat and pericardial oedema were considered a humane endpoint and fish were humanely killed once this was noted and confirmed.\n\nEmbryos/larvae were removed from the CO2 incubator daily (between 09:30 and 10:30, for <15 minutes) and checked for survival and stages of development (Kimmel et al., 1995): tail detachment and somite formation at 24 hpf, heartbeat and hatching success at 48 hpf, and response to touch and body shape scored between 1-5 (Brannen et al., 2010) at 72 and 96 hpf. Survival rate >80% is required in system water to allow for validity of test results, as per the OCED FET assay No. 236 guidelines (OECD, 2013). Salt solutions were kept at 28±1°C and were bubbled every morning for at least 30 minutes to reach the desired CO2, then 1 ml of water from the well was replaced with fresh bubbled solution and the well plate returned to the CO2 incubator and the order was switched around to ensure the same plate was not always in the same spot in the incubator.\n\nAt 98 hpf larvae were anesthetised using Tricaine (MS-222 4 g/L) until movement stopped (~5 minutes). They were imaged on a Nikon SMZ1500 bright-field microscope at 2X magnification and total lengths were measured for larvae with body shape 5, using Fiji (ImageJ) software (Schindelin et al., 2012), from the tip of the head to the end of the caudal fin. Larvae order were randomised prior to imaging using the random number generator function in Excel. The researchers were blind to treatment allocation during imaging and length measurement, but not during daily checking of developmental milestones.\n\nExperiment 1: Analar grade salts and CO2\n\nA single stock solution was prepared weekly using 5 mM NaCl, 5 mM CaCl2•2H2O, 1.8 mM MgSO4•7H2O, 0.5 mM potassium sulphate (K2SO4), and 5 mM NaHCO3 in ultrapure (MilliQ) water by adding each salt one at a time and completely dissolving it before adding the next one. The stock solution was then diluted to achieve 250 ml of the following nominal sodium concentrations of 5, 50, 100, 200, 500, 1,000, 2,000, 5,000 and 10,000 μM every other day (to ensure less than 20% deviation from nominal values, OECD, 2013) corresponding to the treatments of this experiment. Clean “system water” from the Aquatic Resources Centre (ARC) was used as an additional control. Each solution was gassed to one of the four respective experimental partial pressures of CO2 (pCO2) and maintained at 28±1°C in a temperature-controlled room. The pCO2 measured in this study will be referred to generally as CO2 hereafter.\n\nThe nominal CO2s were 400, 2000, 4000, and 8000 μatm, achieved using AALBORG Mass flow Controllers (CACHE instrumentation, UK), flow range 0–200 ml min−1 for CO2 and 0–10 L min−1 for air flow from an air pump (MEDO LA-45B). These gas combinations flowed through a CO2 incubator with a sealed lid. Embryos/larvae under treatment were kept in 1ml of solution in 12-well plates, within the gas-tight incubator. The solution was bubbled for 15-30 minutes prior to exposure to allow levels to stabilise with the respective CO2 flow. Preliminary experiments showed this method kept consistent CO2 levels within the solution.\n\nExperiment 2: Commercial marine salts and CO2\n\nStock solutions of a commercial marine salt at a salinity of 35 parts per thousand (ppt) were prepared weekly by dissolving either Instant Ocean or Tropic Marin commercial salts in ultrapure (MilliQ) water. Stock solutions were diluted twice a week to achieve 6 different “freshwater” salinities of 0.08, 0.16, 0.32, 0.64, 1.2 and 2.0 ppt equivalent to sodium concentrations of 1,250, 2,500, 5,000, 10,000, and 20,000, and 30,000 μM. In this experiment E2 and E3 media (Nüsslein-Volhard and Dahm, 2002) were used for additional comparison. Each solution was gassed to one of three different partial pressures of CO2 (pCO2) of 400, 2000, and 4000 μatm as described above and maintained at 28±1°C.\n\nTemperature (Model HI 8424 Hanna Instruments, Leighton Buzzard, UK) and pH meter (Model HI 8314, Hanna Instruments, Leighton Buzzard, UK, calibrated with HACH buffers) with a red rod pH electrode (HACH, PHC705) in the individual salt solutions, were measured twice a week. Water samples (12 ml) were collected and preserved as described above. The pH and temperature were measured twice weekly in the well water, by retaining the 1 ml waste collected from each treatment and pooled to obtain a sufficient volume for measurement. Levels of CO2 were calculated as described above. Separate water samples were also taken for later analysis of ion concentrations using ion chromatography (Dionex ICS-1000 and ICS-1100).\n\nStatistical analysis on the effect of salt concentration and CO2 and their interaction on zebrafish larvae length, was analysed using the PERMANOVA+ (Anderson, 2008) add on in PRIMER 6.1 (Clark and Gorley, 2006), but can be performed using R. Data were tested to ensure homogeneity of variance, and a similarity matrix was constructed using Euclidean distance. P-values were calculated using 9999 permutations, and pair-wise comparisons were made to see differences between CO2 and salt concentration factors.\n\n\nResults\n\nOf the 40 institutions surveyed, 35 institutes used pure water derived from reverse osmosis (RO), 1 used deionised water (DI), 1 used a combination of reverse osmosis and/or deionised water (RO/DI) and 4 used dechlorinated water (Figure 1A). To this water, either commercial marine salts (36/40 Institutes) or Analar grade salts (3 institutes) were added to create “system water” (Figure 1B). However, one institute used dechlorinated local water without any salts added. Eleven varieties of the commercial marine salts were used, with the most common being ‘Instant Ocean’ (22 institutes) followed by Tropic Marin Centre reef salts (TMC 4 institutes) (Figure 1C).\n\nType of make up water used; B) Type of salts used to make up system water; C) Type of commercial salts used to make system water for facilities that use commercial marine salts (most surveyed). RO = reverse osmosis, DI = deionized water.\n\nThe target temperature of the facilities surveyed varied from 26 to 28.5°C, with a mean of 27.7±2.6°C (Figure 2). The minimum acceptable temperature was 24°C and the maximum was 31°C among all institutes surveyed. For a chosen target temperature, the minimum range was 0.8°C and the maximum range was 6°C. The target pH varied between 7.0 and 8.1, with a mean of 7.3±0.6 (Figure 2). The minimum acceptable pH reported was 6.0 and the maximum was 8.4 among all institutes surveyed. The acceptable pH range varied from 0 to 1.8 pH units within an institute. The target conductivity of the facilities surveyed varied from 300 μS/cm to 1350 μS/cm (equivalent to salinities of 0.13 – 0.65 ppt), with a mean of 667 ± 156 μS/cm (0.30 ppt). The minimum acceptable conductivity was 300 and the maximum was 1500 μS/cm (0.13 and 0.73 ppt, respectively) among all institutes surveyed. The acceptable conductivity range (deviation from mean) varied from 30 μS/cm to 450 μS/cm within an institute. Based on the reported target conductivity, we estimated the sodium concentrations of the system water of all the institutions surveyed. This suggests a minimum Na+ concentration of 0.65 mM and a maximum of 11 mM, with an average of 4.95 mM. Of all the institutions surveyed only one routinely measured pCO2.\n\nNote: the data is ordered in terms of target water parameter (temperature, pH, or conductivity) followed by range, therefore x-axis (order of institutes) is different between panels. Dashed lines in the violin plots represent median values, and the dotted lines represent quartiles (in D the median and upper quartiles are the same).\n\nThe most common freshwater media used for raising zebrafish up to 5 dpf (independent feeding) was E3 (4.96 mM Na+), followed by system water (which was rarely the same composition between institutes and ranged from 3.2 to 11 mM Na+) and egg water (0.8 mM Na+ or 0.06 ppt; Westerfield, 2007). Most facilities (26 institutions) grew the larvae in system water in static tanks between 5 dpf and 14 dpf, and these were transferred to a recirculating system using system water between 14 and 22 dpf. The second most common practice (at 5 out of 40 institutions) for raising zebrafish larvae between 5-14 dpf was a polyculture system, growing these together with marine rotifers and algae at salinities of 2 to 7 ppt. Based on the salinities used we estimate that the sodium concentrations varied by 75-fold between institutions between 0 and 5 dpf, by 122-fold between 5 and 14 dpf, and by 17-fold between 14 and 22 dpf. The largest variation in sodium concentration within an institution was 86-fold between eggs and 5-14 dpf larvae. In one institution, based on the transfer of 14 dpf larvae from 7 ppt to a recirculating system using system water, we estimated that these larvae would experience a dramatic 20.5-fold change in sodium concentration over a course of approximately 24 hours.\n\nThe water samples taken from the 3 major zebrafish facilities in the UK revealed considerable variability in their carbonate chemistry (Table 2). These were compared to water samples from our own facility at Exeter for reference (Table 3). The pH in the 3 major UK facilities was between 6.29 and 7.20, with a mean of 7.12. The pCO2 varied between 1,468 and 2,826 μatm, with an average of 1,984±431 μatm. The alkalinity varied between 53 and 613 μM, with an average of 372 μM. Our facility, which had gone through a recent expansion and therefore had low fish densities by comparison to those sampled had average values of 7.0, 465 μatm, and 253 μM for pH, pCO2 and alkalinity.\n\nIn this experiment, we exposed zebrafish to 9 different levels of Analar grade salt concentrations (5 to 1000 μM Na+) at 4 different CO2 levels (400 to 8000 μatm CO2) to investigate how salinity and CO2 affect the growth and early development (0-4 dpf) of zebrafish. Fertilisation success of embryos in all treatments was >87%, above the required 70% (OECD Test No. 236: FET, 2013). In all the treatments survival was above the required 80 % (OECD Test No. 236: FET, 2013), and above 91% except for the larvae exposed to the lowest sodium level (5 μM) and 4000 μatm CO2 which had 83% survival. Zebrafish developed normally, showing tail detachment, somite formation, hatching success and heartbeat, regardless of salt and CO2 treatment (Supplemental material Table S7). Zebrafish larvae exposed to 5 μM Na+ and 4,000 μatm CO2 had a reduced response to touch (Supplemental material Table S7). By 4 dpf, ~40% of the larvae had an inflated swim bladder, except those exposed to 5 μM, in which almost none had an inflated swim bladder (Supplemental material Table S7). Swim bladder inflation was also lower in larvae exposed to 2,000, 4,000 and 8,000 μatm CO2 compared to those exposed to 400 μatm CO2.\n\nLarval length at 4 dpf varied between 3,239 μm and 4,150 μm (Figure 4) and was significantly affected by both CO2 and salt concentration (p<0.0001 for both), and the interaction between CO2 and salt concentration was not significant (p=0.071). Generally, at all CO2 levels larvae exposed to lower salt concentrations (5 to 100 μM) were significantly smaller by ~5% than those exposed to intermediate and higher concentrations or the system water. Larvae exposed to 2,000 and 4,000 μatm CO2 were 2.2 and 2.7% longer than those exposed 400 and 8,000 μatm CO2, respectively.\n\nAs most facilities use commercial salts, we repeated the above experiment using 2 different commonly used marine salts (Instant Ocean and Tropic Marin®) at 6 different salinities (0.08, 0.16, 0.32, 0.64, 1.2 and 2.0 ppt for each one) and 3 different CO2 levels. Average fertilisation success was >85%. The average survival was above 95% in most experimental treatments; however, the survival of zebrafish larvae exposed to 4000 μatm CO2 was generally lower (only 83%) especially when exposed to lower or higher salt concentrations (0.08, 0.16 and 2.0 ppt). Zebrafish developed normally, showing tail detachment, somite formation, hatching success, heartbeat, and response to touch regardless of salt and CO2 treatment (see Supplemental Material Table S8). Similarly to experiment 1, larvae exposed to the lowest salt concentrations (IO 0.08 and TM 0.08) had the lowest rates of swim bladder inflations compared to those larvae exposed to higher salt concentrations (see Supplemental Material Table S8). Swim bladder inflation was also lower in larvae exposed to 400 and 4,000 μatm CO2 compared to those exposed to 2,000 μatm CO2.\n\nLarval length at 4 dpf varied between 3,267 μm and 4,015 μm (Figure 5) and was significantly affected by pCO2 and salt concentration (p<0.001 for both), but not brand of commercial salt, and the interaction between pCO2 and salt concentration was not significant (p=0.739). Overall, zebrafish larvae exposed to the intermediate CO2 level of 2,000 μatm were 1 to 2% longer than those exposed to 400 μatm CO2 (control) and 1 to 3.5% longer than those exposed to the highest CO2 of 4,000 μatm (Figure 5).\n\n\nDiscussion\n\nOur survey confirmed that there was considerable variability in the water chemistry used between different institutions (Figures 1-3), with ion concentrations varying as much as 122-fold between institutions at certain life stages. In lab experiments, we tested a large range of salt concentrations that spanned the entire range encountered in these facilities in combination with 3 to 4 different pCO2 concentrations and found that zebrafish larvae exposed to low salt concentrations developed normally, but were smaller than zebrafish exposed to higher salt concentrations (Figures 4, 5). Additionally, larvae exposed to different pCO2 concentrations did not have any developmental abnormalities, but those exposed to intermediate levels of pCO2 were the longest suggesting faster growth. Overall, zebrafish larvae were robust in terms of their development and growth when exposed to a large range of salt and CO2 levels, but what effects these early exposures may have on later developmental stages needs further investigation.\n\nOf note: the system water refers to the standard water used for housing fish in each facility, but the salt concentrations in these systems varied by up to five-fold, therefore not one standardized recipe.\n\nDifferent lower case letters above a salt concentration indicate significant differences between these salt concentrations (p<0.05), those that share at least one letter are not significantly different than one another; length was significantly different between all pCO2 levels (p<0.05). Exeter refers to the system water at the University of Exeter which was used as a reference.\n\nDifferent lower case letters above a salt concentration indicate significant differences between these salt concentrations within salt treatments (p<0.05), those that share at least one letter are not significantly different than one another; * indicate significant differences from E2 (p<0.05), † indicate significant differences from E3 (p<0.05). Length was significantly different between all pCO2 levels (p<0.05). IO indicates Instant ocean and salinity level in ppm, TM indicates Tropic Marine and salinity level in ppm. E2 and E3 refer to the freshwater media used in zebrafish research (see Nüsslein-Volhard and Dahm 2002).\n\nMost institutions (36) reported using reverse osmosis (RO) water as the basis for their system water, with only four institutions choosing to use dechlorinated water. In all but one institute (that used dechlorinated tap water), salts are then added to reconstitute the water to their desired recipe. The institute using dechlorinated water without additional salts is located in an area with very hard water and presumably contains sufficient salts for the welfare of zebrafish. However, the chemistry of dechlorinated tap water varies enormously with local geology, and even in the same place it varies over time with the seasons/weather and depending on the source reservoir being used and operational changes at the mains water plant. Therefore, its consistency is not guaranteed spatially or temporally with potentially important consequences for experimental outcomes and reproducibility of studies. Using RO water is more costly and results in higher total water usage due to the portion discarded by the RO filtration process. On the other hand, by using RO water reconstituted with added salts, zebrafish facilities are better able to standardise and control their system water conditions. In our survey, during the stages to independent feeding (< 5 dpf) fish were exposed to the most diverse range of freshwater media types across institutions (Figure 3A). For larvae from 5 to 21 dpf the number of freshwater media types decreased with the system water becoming the dominant choice (Figure 3B). With the exception of one facility, all larvae post 21 dpf were transferred to system water following this life stage (Figure 3C). Notably, larvae from 5 to 21 dpf are likely to be exposed to the greatest variation in ion concentrations during this life stage with up to a 87 fold change in Na+ concentration (Figure 3D). Additionally, many institutions reported switching (from using previously published freshwater media such as E2, E3, embryo water and Danieau’s solution for embryos and larvae) to system water. This switch to system water is likely driven by convenience as well as the ability to achieve a more consistent system water composition over time within a given institution.\n\nMost institutions maintained conductivity, pH and temperatures within the recommended range for zebrafish of 150 to 2,000 μS/cm (Goodwin et al., 2016; Harper and Lawrence, 2011; Martins et al., 2016), pH of 6.5 to 8 (Aleström et al., 2020), and 24 to 31°C (Westerfield, 2007), respectively. However, these ranges are wide, with the H+ concentration varying by 32-fold and conductivity by 13-fold between the lowest and highest recommended values, respectively. These ranges are consistent with the wide variation in water chemistry that zebrafish are adapted to in their natural environment (Aleström et al., 2020). However, they are still sufficiently large to be biologically significant and so we propose that these should be narrowed across zebrafish facilities to minimize variation in phenotypes, although more research is necessary to confirm the quantitative significance of this suggestion. A striking discovery from the survey was the relatively wide variation in salinity that zebrafish larvae were exposed to in a relatively short period of time (2 weeks) and during critical stages of development. We did not test the effects of these large temporal changes in salinity on growth or development, but this warrants further investigation to determine if such large fluctuations could have effects lasting into the juvenile stage or adulthood. A current study over the whole life cycle aims to determine what water chemistry is optimal based on growth, physiological and behavioural performance indicators. Such studies are needed before guidelines and recommendations can be made for facilities to adopt.\n\nThe pCO2 in the water samples taken from three major zebrafish facilities varied between 1,468 and 2,826 μatm, much higher both maximum and range than the 450 to 1,200 μatm previously reported at four different biomedical facilities in Sweden (Vossen et al., 2016). These partial pressures are almost 3 times as high as the pCO2 predicted in the atmosphere and surface ocean for year 2100 under a business-as-usual scenario of anthropogenic CO2 emissions (IPCC, 2013). However, pCO2 levels vary much more in freshwater environments (Weiss et al., 2018) due to variations in local geology, water cycle, vegetation, and climate (McNeil and Matsumoto, 2019). High pCO2 values up to 10,000 μatm are common in both freshwater and marine recirculating aquaculture systems (RAS) used for intensive aquaculture (Ellis et al., 2017). The facilities used for the culturing zebrafish are very similar in principle (but usually smaller in scale) to those used in large-scale aquatic food production systems because many thousands of fish share the same recirculating water. However, but perhaps not surprisingly, in our experiments zebrafish larvae exposed to 2000 μatm were the longest. These pCO2 values are well within those reported for zebrafish in the wild (~4500 μatm) (Sundin et al., 2019). It is unclear whether the larvae grew best at 2000 μatm because they have been exposed to this level over several generations in a laboratory setting or because they have evolved in a high pCO2 environment in the wild, or both. Therefore, ambient levels of pCO2 (i.e., the lowest used in our experiments; 400 μatm) often deemed the “norm” and employed as the control condition in climate change studies in various fish species, may not provide optimum growth in zebrafish and perhaps should not be targeted in zebrafish facilities. However, longer duration exposures than just these early life stages will help expand our understanding of optimal CO2 levels for zebrafish more generally.\n\nNone of the salt concentrations used in either experiment limited the ability of zebrafish to reach different developmental stages, but potential negative effects on swim bladder inflation were observed at low the lowest salt concentrations when combined with high pCO2 of 2000 μatm and above (Experiment 1, Supplementary table S7) or at 400 and 4000 μatm CO2 (Experiment 2, Supplementary table S8). As measurements were done at 4 dpf it is unclear if any fish would still lack an inflated swim bladder at 5dpf when zebrafish larvae are generally placed in nursery tanks with deeper water. If so, this would increase mortality rates due to inability to reach the surface of the deeper water to inflate their swim bladder or impair swimming. Therefore, careful monitoring of swim bladder inflation might be particularly important for those labs or institutions that use water from their racks to raise zebrafish larvae as it tends to be higher in pCO2 than freshly made media (i.e. E2 or E3). Furthermore, zebrafish larvae exposed to the lowest salt level in each of experiments 1 and 2 (5 μM Na+ and 0.08 ppt sea salt, respectively) were shorter than those exposed to intermediate salinities (500 to 2,000 μM Na+ in Experiment 1, and 0.32 to 1.3 ppt sea salts in Experiment 2) and similar in size to those exposed to high salinities (1 mM Na+ in Experiment 1, and 2 ppt in Experiment 2), indicating that intermediate salt concentrations provided the optimal growth in zebrafish larvae. Freshwater fish need to actively uptake ions from the external water in order to maintain ionic homeostasis, and the active transport processes usually follow classic Michealis-Menten kinetics (Potts, 1994), i.e. a steep rise followed by a plateauing of the active ion uptake rate as the external water ion concentration increases. Thus, zebrafish exposed to low salt concentrations will have impaired capacity for active ion uptake (Kwong and Perry, 2013; Kwong et al., 2013) and may be compromised in their ability to fully compensate for the constant passive diffusive ion losses, but studies to date have not assessed ion regulation in zebrafish larvae exposed to such low ion concentrations (5 μM Na+). However, it is conceivable that zebrafish larvae could compensate for living in a low salinity environment once feeding independently by obtaining additional salt from their food, as seems to be important in many fish species that live in ion poor waters (Gonzalez et al., 2005). But this warrants further investigation for zebrafish. Although high salinity of more than 2 ppt could affect zebrafish growth by impairing nuclear division of the embryonic cells during early development (Sawant et al., 2001), salinity levels of around 2 ppt have been reported to cause the most rapid growth ever reported in zebrafish when combined with constant light conditions and live rotifer feed (Dabrowski and Miller, 2018).\n\nZebrafish can detect high CO2 levels of >10,000 μatm CO2 using neuroepithelial cells in their gills (Qin et al., 2010) or levels of > 30,000 μatm CO2 through the terminal nerve near the olfactory epithelium (Koide et al., 2018). These high CO2 levels induce a slow avoidance behaviour in zebrafish larvae (Koide et al., 2018), but they are much higher than those we report here for 3 UK research facilities or for zebrafish habitats in the wild (Sundin et al., 2019). However, a study looking at levels of CO2 that more closely resemble those reported here for research facilities found that zebrafish adults exposed to 1600 μatm CO2 exhibited a stronger turning preference (lateralization) than those fish exposed to 400 μatm CO2 (Vossen et al., 2016). This is opposite to that found in marine fish which show a reduced turning preference at higher CO2 (1000 μatm) compared to ambient CO2 (400 μatm) (Domenici et al., 2012). Having a preference for turning one way over another (i.e. being lateralized) is considered to be more normal for fish than not having a preference. These findings therefore may indicate that 1600 μatm CO2 is the more common condition for zebrafish (or to what they have adapted to) and that 400 CO2 μatm is perhaps the more unusual condition. Furthermore, exposure to 1600 μatm CO2 did not affect the activity of adult zebrafish compared to those exposed to 400 μatm CO2 (Vossen et al., 2016), but higher pCO2 levels were not tested, and neither were other stages of development.\n\nTherefore, levels of pCO2 encountered in research facilities could affect behaviour of zebrafish, as indeed may sudden transfer between waters of different pCO2 (as may occur when conducting behavioural assays or drug or toxicant exposures in different water to the home tank). However, further studies are necessary to determine if this is the case, at which stages of development this might be happening and at what pCO2 levels, keeping in mind that ambient CO2 (~400 μatm) may not necessarily represent the control condition for zebrafish.\n\nLonger term studies in other fish species suggest that low salt levels act as a mild environmental stressor with a higher cost of living indicated by detrimental changes in growth, feeding and protein turnover (Reid et al., 1995), whilst longer term exposure to elevated CO2 can also compromise growth with adverse effects on immune function genes, thinner skin (dermis and epidermis) and fewer mucous cells, with implications for defence against infectious agents (Mota et al., 2019, 2020). Future work will involve full life-cycle (embryo to adult) exposure of zebrafish to a range of salt and CO2 environments such that we can investigate the impacts of these variables on multiple life history stages, and end points that matter the most to zebrafish facilities. End points will include growth rate, fish condition and time to maturation; reproductive success, most notably egg output and gamete quality; physiology of ion regulation and its impact on, for example, acid-base regulation in response to routine husbandry stresses, feed conversion efficiency; and immune function which impacts the health/robustness of the population during to day-to-day husbandry practices and susceptibility to infection in large shared recirculating systems.\n\n\nConclusions\n\nHere we highlight the variability in water chemistry used to house zebrafish for scientific research despite their use since the 1960’s. We show that these variations can lead to changes in growth of embryos up to 4 dpf but whether these changes manifest in later life performance or have the potential to impact the outcomes of research studies needs further investigation. At intermediate levels of CO2 (2000 μatm) larvae were significantly longer, but also tended to have lower swim bladder inflation rates when water was made with Analar grade salts. Therefore, higher CO2 levels might have both positive and negative effects on zebrafish larvae and particular attention should be paid to swim bladder inflation before zebrafish are transferred to deeper water as this is critical for larval survival and performance. Moreover, CO2 levels that are too high reduced the growth of zebrafish larvae and this is consistent with previous research showing salmon larvae exposed to high CO2 had a reduced efficiency of conversion of yolk into growth (Ou et al., 2015). Additionally, as current guidance is variable and often vague (Lee et al., 2022), we highlight the lack of information to inform guidance for zebrafish welfare. As there are over 5 million adult zebrafish used for research annually worldwide (many more if larvae younger than 4 dpf are considered), optimizing and standardizing water chemistry parameters presents an opportunity to improve zebrafish welfare. This would be through refinement due to improved fish health. Narrower ranges of water chemistry would reduce the number of fish growing in suboptimal conditions (too low or too high salinity, CO2, pH or temperature) as these fish would be investing more energy into maintaining homeostasis and, therefore, have less energy available for growth, development or to mount an immune response. Additionally, this variability in energy allocation could lead to increased variability in responses during experimental measurements increasing the variability, sample size and use of zebrafish for research purposes. Therefore, a reduction of just 5% of the zebrafish used in research due to more optimal husbandry water chemistry conditions would represent over 250,000 fewer fish being used as a consequence of decreased variability of results and improved replicability. Therefore, we propose that a better understanding of what drives facility choices in the water chemistry ranges they adopt is needed. We propose that these choices are aligned better with peer-reviewed scientific evidence if we are to optimise and standardise approaches between institutions, develop best practice for fish welfare, improve performance and reduce the potential causes of reproducibility problems in research using zebrafish. Institutions are currently measuring several important water chemistry parameters, but these are often not reported (or not reported accurately) in the methods section of scientific outputs. As a minimum, we recommend that researchers report temperature, pH, conductivity and the nominal recipe for the freshwater media used for their stock as well as experimental animals used, and ideally this should be confirmed by direct measurement of the biologically important inorganic ions if possible (especially sodium, chloride, calcium) as well as alkalinity.\n\nAll experiments were carried out in the University of Exeter Aquatic Resources Centre (ARC), and procedures were approved by the Home Office (License No P88687E07) and reviewed by the University of Exeter Ethics (Application ID 5542334). All relevant information has been reported in the body of the manuscript in line with the ARRIVE 2.0 guidelines developed by the NC3Rs, including our efforts to ameliorate any suffering of animals.",
"appendix": "Data availability\n\nThe underlying data has been deposited in Figshare: https://doi.org/10.6084/m9.figshare.22644607.v1 (Porteus et al., 2023).\n\nThis project contains the following underlying data:\n\n• Porteus et al F1000 all raw data.xlsx (Data file 1 includes all the raw data from the survey responses and Experiments 1 and 2)\n\n• Supplementary materials file.pdf (Supplementary materials file)\n\n• ARRIVE Author checklist.pdf (ARRIVE guidelines)\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 the Aquatic Resources Centre at the University of Exeter for provision of embryos, assistance with fish husbandry and maintenance of aquarium facilities. We would also like to thank Dr Jonathan Ball for expertise in the use of the FET assay and in establishing the end points, Tecniplast with help in distributing the survey, Arsheen Bozai for summarizing the water chemistry and developmental data, Carol Lee for helpful comments on a draft of the manuscript, and Dr Rob Ellis for help with the statistical analysis.\n\n\nReferences\n\nAleström P, D’Angelo L, Midtlyng PJ, et al.: Zebrafish: Housing and husbandry recommendations. Lab. Anim. 2020; 54: 213–224. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnderson MJ: Permanova+ for Prime: Guide software and Statical methods.2008.\n\nBrannen KC, Panzica-Kelly JM, Danberry TL, et al.: Development of a zebrafish embryo teratogenicity assay and quantitative prediction model. Birth Defects Res. B Dev. Reprod. Toxicol. 2010; 89: 66–77. 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}
|
[
{
"id": "264114",
"date": "30 Apr 2024",
"name": "Lynne Sneddon",
"expertise": [
"Reviewer Expertise Zebrafish welfare",
"Fish behaviour and physiology"
],
"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 very interesting article reports on a hot topic in zebrafish husbandry and concerns standardisation of water quality. It is well known that there are a range of water quality parameters that zebrafish can tolerate and thrive in but there are great disparities between facilities due to care staff employing the most effective means of keeping the fish. Typically, facilities use what works and what they can afford. However, this provides cause for concern since this may affect reproducibility or replicability between laboratories. This article seeks to highlight the variable approaches across institutions and then focuses on NaCl and CO2 as factors that may affect development of zebrafish up to 4 days post fertilisation. First a survey is conducted which provides insight into the variability of water quality parameters that facilities are adopting in zebrafish husbandry. Secondly, three institutions are sampled for CO2 analysis and finally an experiment is conducted using high grade salts versus commercially available marine salts combined with differing CO2 levels. The experiments demonstrate that low NaCl using high grade salts affects length and in both salt formulations swim bladder inflation is impaired. Slightly elevated CO2 (2000 atm) appears to increase length at some CO2 concentrations. CO\" at 4000 atm has a negative impact on length. In the three institutions sampled, they range from ~1500 to 2800 - I wonder if this is due to the use of sodium bicarbonate that is largely employed in commercially systems to maintain pH - can the authors comment on the fact that this can elevate CO2 above ambient (400 atm)? These seem high to me and would suggest then the life support systems are inadequate for dealing with CO2 - can you please suggest the use of additional aeration or degassing systems in the discussion - get rid of the CO2 = get rid of the problem? Or do you think based on your 4 dpf results these higher than ambient CO2 concentrations are beneficial? Of course many facilities do not keep larval fish on their main systems so as it is you can only suggest these CO2 levels up to 4 dpf. These could have negative consequences on adults but then they are coming from probably large, successful facilities. One of the key issues that should be mentioned possibly in the introduction is that zebrafish are largely used for biomedical studies where the researchers want the animals to be kept at standard or constant environmental conditions - there is an emphasis on environmental studies and toxicology in the article but I think this is a good selling point that for biomedical experiments we need agreed water quality parameters between labs. Can you add statistical analysis to compare between the salts - perhaps it is the way it is written but these are treated like two different experiments and yet really we need to know how they compare. Are we doing the right thing for the fish by using commercially available marine salts or should we use the more precise methods of high grade salts? When looking at the two figures on length it would seem only the low concentrations of high grade salts affect growth and actually this would convince me marine salts are possibly more beneficial. Further was there any difference between salts - it seems from the graph that IO may be better than TM? Overall I think this is a very useful article that can promote standardisation across facilites and highlights the impact of water quality on growth in 4 dpf as well as other factors such as swim bladder inflation. This could help facilities trouble shoot high mortality rates in larvae and provide an avenue of investigation for the improved survival of larval zebrafish. I have some very minor comments and suggestions: Abstract, Background - delete importantly as important used in previous sentence. Abstract, methods: Add \"water chemistry parameters\" Throughout the manuscript you should add mg/l for CO2 and NaCl concentrations as this is what they are measured in by most water quality probes. Abstract, Results: Change to \"swim bladders did not\" Introduction Line 1: change ion levels to dissolved ion concentrations End of paragraph 1: regained would be a better word than recovered and I am not sure what \"more completely\" means here so I suggest delete. \"restoring\" - would maintaining be better and was this an experiment so can you add the citation? Paragraph 2 -there is a statement on CO2 accumulation - this needs citations You use the word cope but just because an animal can cope or tolerate does not mean they are in good welfare? Ca you please add a statement somewhere about this - yes zebrafish can tolerate or cope with a range - it does not mean they are in a good physiological state. I would add a sentence to the end of the 2nd paragraph along the lines of \"The impact of CO2 or its interaction with NaCl is not clearly understood due to a lack of studies on zebrafish\" Table 1 - can you provide conductivities? Again mM is not that useful for measuring using commercial aquarium probes - can mg/l be added? Survey - I can't seem to access the SI but if not there it would be really useful to have the survey in this section so it could be repeated. Water samples - does freezing affect these variables you measured? Humane endpoints - would be useful to detail the average % of larvae that reached this point. Results page 7 - can you delete dramatic as it's rather emotive. Discussion, L2 should be laboratory P12 typo \"the culturing OF zebrafish\" Delete but perhaps not surprisingly Change \"measurements were done\" to measurements were carried out P13 L1-4 you didn't measure lateralisation or preference for turning - it's not mentioned previously so I suggest delete. P13 2nd paragraph delete Therefore as its a new paragraph - alternatively merge with previous. Conclusions: CO2 levels that are too high - please give a value to this. Mention the ARRIVE guidelines that encourage full reporting of 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? 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": "12220",
"date": "20 Aug 2024",
"name": "Cosima Porteus",
"role": "Author Response",
"response": "“I wonder if this is due to the use of sodium bicarbonate that is largely employed in commercially systems to maintain pH - can the authors comment on the fact that this can elevate CO2 above ambient (400 atm)?” Response: The addition of sodium bicarbonate in recirc systems is typically to modify pH to compensate for the acidification as CO2 accumulates. You are right that whilst this brings pH back up somewhat, it can actually increase the water pCO2 as well, as some of the bicarbonate is converted to CO2 by the excess H+ ions in the water. However, if degassing is sufficient, water pCO2 should return to close to atmospheric levels (400 uatm), but clearly this is not happening in the zebrafish facilities we sampled. In some large scale RAS (e.g. salmon, trout) they use other sources of alkali (e.g. NaOH) which does not add more CO2 whilst buffering pH. However, using caustic soda in this way presents health and safety issues for the staff, so it is a trade off. We do not feel this is information that needs to be added to the manuscript but we offer it here in response to the reviewer. “These seem high to me and would suggest then the life support systems are inadequate for dealing with CO2 - can you please suggest the use of additional aeration or degassing systems in the discussion - get rid of the CO2 = get rid of the problem? Or do you think based on your 4 dpf results these higher than ambient CO2 concentrations are beneficial?” Response: These CO2 levels found in zebrafish facilities are not actually high relative to what we find in commercial aquaculture for food species (e.g. salmon, trout) where 2,000 µatm is the lowest we have seen, and typically it is closer to 5,000 to 10,000 µatm as a typical range. However, better degassing would certainly enable lower pCO2 values in any system, zebrafish included. As the reviewer comments, we do not yet know all the evidence regarding what the most optimal CO2 level is for zebrafish, so we should probably wait until such data are available before making specific recommendations about adding more degassing etc. “Can you add statistical analysis to compare between the salts - perhaps it is the way it is written but these are treated like two different experiments and yet really we need to know how they compare. Are we doing the right thing for the fish by using commercially available marine salts or should we use the more precise methods of high grade salts? When looking at the two figures on length it would seem only the low concentrations of high grade salts affect growth and actually this would convince me marine salts are possibly more beneficial.” Response: The reviewer makes a good point that to truly compare these we would need to compare them statistically. However, the experiments were done separately and if any statistical differences were found these could be due to slight differences in ambient temperature, the ratio of the different salts, or differences in embryo batches/parents and, therefore, these analyses were not run. Overall, the embryos seem to grow well in both salt treatments and we don’t see any benefits to using high-grade salts, and we recommend the marine salts as they are more cost-effective and convenient to use than the high-grade salts. “Further was there any difference between salts - it seems from the graph that IO may be better than TM?” Response: We initially ran a nested ANOVA with salinity nested within brand that revealed there were no statistical difference between brands. However, we were not able to compare with the two control solutions (E2 and E3) in this analysis. Therefore, we used a two-way ANOVA with salt treatment and PCO2 as factors to allow us to perform an all-pairwise comparison including the control solutions. This analysis indicated significant differences at the lowest and highest salinity (0.08 and 2.0 ppt), and we are indicating this in Figure 5. However, since the middle salt concentrations were not different and the nested ANOVA indicated no significant difference, we concluded that differences between salt brands are negligible. We have also uploaded the statistical results from both analyses as files in a separate Figshare submission. Abstract, Background - delete importantly as important used in previous sentence. Response: changed to “Notably”. Abstract, methods: Add \"water chemistry parameters\" Response: Changed. Throughout the manuscript you should add mg/l for CO2 and NaCl concentrations as this is what they are measured in by most water quality probes. Response: We have added two new rows to our Table 1 that shows the conductivity in µS/cm for each solution (this measures a substance’s ability to conduct electricity and cannot be broken down by individual ion) and one row to show the salinity in ppt. This is what most probes measure. We have also added values in mg/L in the methods and abstract to make it easier to compare pCO2 levels. Abstract, Results: Change to \"swim bladders did not\" Response: Changed. Introduction Line 1: change ion levels to dissolved ion concentrations Response: Changed. End of paragraph 1: regained would be a better word than recovered and I am not sure what \"more completely\" means here so I suggest delete. \"restoring\" - would maintaining be better and was this an experiment so can you add the citation? Response: We have removed “more completely” from this sentence and citations have been added. We simply meant that fish recovered faster to an acid-base disturbance such as elevated CO2 when the water they were in had higher ion concentrations. Paragraph 2 -there is a statement on CO2 accumulation - this needs citations Response: Citation added. You use the word cope but just because an animal can cope or tolerate does not mean they are in good welfare? Ca you please add a statement somewhere about this - yes zebrafish can tolerate or cope with a range - it does not mean they are in a good physiological state. Response: We have changed the sentence to read “However, just because zebrafish can tolerate these pCO2s, they might not be in a good physiological state and thus, despite the ability to regulate blood acid-base balance, living in high CO2 water has further, more holistic impacts on fish performance.” I would add a sentence to the end of the 2nd paragraph along the lines of \"The impact of CO2 or its interaction with NaCl is not clearly understood due to a lack of studies on zebrafish\" Response: Thank you. We have added “However, the are no studies on zebrafish that have assessed the impact of pCO2 or its interaction with NaCl.” Table 1 - can you provide conductivities? Again mM is not that useful for measuring using commercial aquarium probes - can mg/l be added? Response: Yes, added. Survey - I can't seem to access the SI but if not there it would be really useful to have the survey in this section so it could be repeated. Response: The survey is included in the SI. Not sure why the reviewer is unable to access this file. Water samples - does freezing affect these variables you measured? Response: The water samples were not frozen, but stored in the fridge (4°C). Humane endpoints - would be useful to detail the average % of larvae that reached this point. Response: Very few larvae, ~0.5% reached the humane endpoints. We have added this information to the manuscript. Results page 7 - can you delete dramatic as it's rather emotive. Response: Removed. Discussion, L2 should be laboratory Response: Changed. P12 typo \"the culturing OF zebrafish\" Response: Thank you. “of” added. Delete but perhaps not surprisingly Response: Deleted. Change \"measurements were done\" to measurements were carried out Response: Changed. P13 L1-4 you didn't measure lateralisation or preference for turning - it's not mentioned previously so I suggest delete. Response: We argue that this is still a valid point even if we did not measure lateralization, as it shows that zebrafish might be adapted to living in higher pCO2 they show a turning preference at 1600 µatm and not at 400 µatm. P13 2nd paragraph delete Therefore as its a new paragraph - alternatively merge with previous. Response: Merged with previous. Conclusions: CO2 levels that are too high - please give a value to this. Response: 4000 and 8000 µatm have been added in parentheses. Mention the ARRIVE guidelines that encourage full reporting of results. Response: We now refer to the ARRIVE guidelines in our conclusion."
}
]
},
{
"id": "264116",
"date": "03 May 2024",
"name": "Alex Zimmer",
"expertise": [
"Reviewer Expertise Fish physiology",
"Developmental physiology",
"ionoregulatory physiology"
],
"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\nComments on Porteus et al.\n\nPorteus et al. present a study that describes the range of water chemistry conditions that are currently used in zebrafish facilities of many major research institutions across the globe. They highlight the large discrepancy of water chemistry conditions used across these institutions pointing to potential issues with repeatability of studies, which could result in increased unnecessary use of research animals. The authors go on to conduct a study to test this idea wherein zebrafish embryos were reared under differing concentrations of salts and/or CO2 partial pressures that reflect the range used across institutes reported in their survey. In general, their results demonstrate that fish reared under extremely low levels of salts (5 µM Na) showed reduced growth relative to the other concentrations. While other subtle differences were also apparent, these were not as striking as the effects at the lowest salt concentration. Overall, I found this study to be thoughtfully designed and well-implemented. Moreover, I feel that this study will be a useful reference for researchers in the zebrafish community looking to optimize their culture conditions. Indeed, the authors point out many pitfalls (e.g., large changes in salt concentration between life stages) that could be avoided with more careful control of rearing environment. My major criticism with the manuscript in its current form is that I feel that some of the conclusions, for example that all research institutes need to improve control and standardization of water chemistry conditions, are not supported by the data presented. As I discuss in more detail below, I feel like the results could be painted in a more positive light than they are in the current form. Specific comments:\nSmall point (line 3, paragraph 1 in the Introduction), but is it worth mentioning calcium as another important ion that fish must take up from the water? Certainly, this must have important implications for fish growth. Figure 4. The statistical notations in this figure are very hard to decipher as presented. For instance, from my interpretation it seems like the 500 uM Na treatment (noted with “d,e”) is statistically different from the Exeter treatment (noted with “c,f,g”), but this strikes me as hard to believe because some of the CO2 treatments are higher in the 500 uM treatment (400 and 2000 uatm), some are lower in the 500 uM treatment (4000 uatm), and another is more-or-less equal (8000 uatm). I suggest double-checking the notations in this figure for accuracy. Apologies if I have misinterpreted the notations. The authors conclude generally that optimizing and standardizing water chemistry parameters present an opportunity to improve zebrafish welfare, potentially reducing worldwide usage by 250,000 fish per year if changes are sufficient to reduce usage by 5%. While I agree that reducing animal usage in research is important, I feel that the data the authors present suggest that zebrafish are quite hardy and seem to perform well across a wide range of water chemistry conditions (e.g., growth is unchanged across ion concentrations ranging 2-3 orders of magnitude!). Clearly more work is needed to understand whether these differences have knock-on effects later on in development or if they alter immune function or other important welfare parameters. However, in my opinion the data represent a “good news” story: despite large differences in water chemistry used across research institutions, zebrafish growth performance is generally consistent across rearing conditions. The one real difference in the study was observed at 5 uM Na which I imagine would actually be quite hard to achieve in recirculating systems. Therefore, I suggest that the authors might reconsider their conclusion in light of the fact that their findings appear to paint a more optimistic picture regarding the variability of data produced by different research institutes, at least in the context of early life growth performance.\n\nAre the 3Rs implications of the work described accurately? Yes\n\nAre a suitable application and appropriate end-users identified? Yes\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? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12221",
"date": "20 Aug 2024",
"name": "Cosima Porteus",
"role": "Author Response",
"response": "1 – The reviewer is correct that calcium is taken up via the gills from water. However, quantitatively this is less important for freshwater fish than gut uptake of calcium (via the diet). Also, the rate of calcium uptake via the gills is substantially less than that of sodium or chloride uptake via the gills, this was why we focused on sodium in this sentence. 2 – We have double-checked the statistical analysis and we have found a couple of errors in this figure and the figure has now been corrected. The 500 µM salt concentration was significantly different, although only just (p=0.047) than the Exeter water. We have also added our statistical analysis results as separate files to Figshare (see Data availability statement). 3 – We agree with the reviewer that this is a good news story, however, we only measured growth and scored deformities on the larvae, which are quite severe endpoints. Our effects on the growth of larvae show that there are sublethal effects and we caution against using very low salt concentrations as these might have longer lasting effects. However, as the last sentence mentions, our growth data are for up to 4 dpf only, i.e. early stages only, and before exogenously feeding, and so we need more data on what happens next with growth. We are currently running these experiments and hope to report these soon in a separate manuscript, but wanted to report our initial results here. We agree that a sodium level as low as 5 µM will be hard to achieve in a recirc system. However, we can confirm that this was the level predicted based on the salinity reported in a published paper and we contacted the authors who confirmed this was not a typographical error in the paper, therefore we decided to test this level because it was the lowest we could find reported in the literature."
}
]
}
] | 1
|
https://f1000research.com/articles/13-168
|
https://f1000research.com/articles/13-938/v1
|
20 Aug 24
|
{
"type": "Research Article",
"title": "A survey measuring purchase intention towards environmentally friendly products",
"authors": [
"Yuen Yee Yen",
"Tan Zi Ling",
"Tan Zi Ling"
],
"abstract": "Purpose This study examines the key factors affecting consumers’ purchases of environmentally friendly products in Malaysia.\n\nOriginality Although the Malaysian government has put in effort and assistance to promote the use of environmentally friendly products, the purchase of environmentally friendly products remains low, as the costs of environmentally friendly products are still more expensive than those of non-energy efficient products. This study is one of the pioneering studies in developing countries that examined the purchase of environmentally friendly products after the COVID-19 pandemic.\n\nMethodology Three hundred participants from four developed states in Malaysia with the highest awareness of environmental protection and environmentally friendly products were approached. The survey was administered to the respondents in public places.\n\nFindings Malaysians’ purchase intentions towards environmentally friendly products are affected by confidence, family income, and attitude. In contrast, this study found no significant positive effect of financial subsidies on purchase intention towards environmentally friendly products.",
"keywords": [
"Purchase intention",
"environmentally friendly",
"confidence",
"attitude",
"family income."
],
"content": "1. Introduction\n\nOver the last few decades, environmental threats have been alarming for governments and citizens to embrace environmentally friendly products (Kim & Lee, 2023). The use of environmentally friendly products is one way to minimize environmental damage. Environmentally friendly products are considered energy-saving innovations that minimize negative environmental effects (Hung & Chang, 2024). The use of environmentally friendly products is crucial for both developed and developing countries because they play a significant role in alleviating the effects of climate change.\n\nMalaysia has been listed as one of the countries with the highest growth in greenhouse gas emissions (7.9%) over the last 30 years (Abd Aziz et al., 2024). With increasing energy consumption owing to economic growth and improvement in quality of life, Malaysia will face significant challenges in energy conservation, of which environmentally friendly products are one of the best alternatives to reduce greenhouse gas emissions in the country (Salim et al., 2024).\n\nThe Malaysian government has issued special programs, including the Green Income Tax Exemption, to motivate more people to purchase environmentally friendly products. The government has invested RM2.23 billion in the development and promotion of environmentally friendly products (Abd Aziz et al., 2024). However, as of 2024, consumers’ purchases of environmentally friendly products in Malaysia remain low (Abd Aziz et al., 2024; Salim et al., 2024).\n\nConsumers’ attitudes and intentions towards environmentally friendly products are important in Malaysia, as the government has allocated a substantial budget for the development and promotion of environmentally friendly products (Abd Aziz et al., 2024; Salim et al., 2024). It is imperative to conduct the latest research that examines consumers’ judgment at the time of purchasing environmentally friendly products. Nevertheless, Asif et al. (2023) and Hung and Chang (2024) revealed only minimal research examining consumers’ purchase of environmentally friendly products in developing countries, as most of the studies were conducted in developed countries. There is a significant knowledge gap regarding consumer behavior towards purchasing environmentally friendly products in Malaysia.\n\nAlthough the Malaysian government has put in effort and assistance to promote the use of environmentally friendly products, the purchase of environmentally friendly products remains low, as the costs of environmentally friendly products are still more expensive than non-energy-efficient products (Abd Aziz et al., 2024; Salim et al., 2024). However, Aziz et al. (2024) and Salim et al. (2024) did not evaluate whether subsidy incentives have a favorable impact on the purchase of environmentally friendly products, particularly for low-income families, which face financial barriers in purchasing environmentally friendly products after the COVID-19 pandemic.\n\nThis study addresses these research gaps by examining the key factors affecting consumers’ purchase of environmentally friendly products in Malaysia. This study provides a better understanding of consumer purchases of environmentally friendly products. The outcome of this research could serve as a guideline for increasing consumers’ value propositions on environmentally friendly products.\n\nIn addition, this study can benefit renewable energy providers by identifying the most suitable marketing strategies and promotional packages that could improve the level of purchase of environmentally friendly products among Malaysians. The findings can be used to provide guidelines for increasing the perceived efficacy of environmentally friendly products to boost the value proposition to consumers. As a result, consumers’ willingness to embrace environmentally friendly products improves.\n\nThe government and related authorities can also benefit from this study, as they would be able to identify the problem and provide suitable solutions based on real-time data and information about purchasing environmentally friendly products. Thus, the government can produce a suitable action plan that would better suit the needs of Malaysian consumers. The authority can gain deeper insight into issues related to consumers’ purchase of environmentally friendly products and formulate necessary actions to enhance sustainable energy conservation practices in the country.\n\n\n2. Literature reviews\n\nPurchase intention, as defined by Kim and Lee (2023), refers to consumer readiness to acquire equipment or services. In this study, purchase intention towards environmentally friendly products refers to how much effort they are planning to put into acquiring environmentally friendly products.\n\nAccording to Reddy et al. (2023), an individual must establish sufficient knowledge as well as technological and environmental awareness to purchase environmentally friendly products. Consumers with proper knowledge and confidence in renewable energy technology show favorable purchase intentions. environmentally friendly products (Hung & Chang, 2024). The purchase intention for environmentally friendly products change due to the impact of global climate change. Consumers’ buying behavior may be strongly connected to their desire to consume environmentally friendly products (Houf, Szymkowiak, & Shepherd, 2024). Saini et al. (2024) assert that individuals who are more knowledgeable about environmental concerns have a more favorable purchase intention towards environmentally friendly products.\n\nStranieri et al. (2023) defined confidence as the degree to which a person feels assured about his/her marketplace judgments on a product.\n\nAccording to Kim and Lee (2023), confidence can be conceptualized into two categories: knowledge confidence and choice confidence. Knowledge confidence is determined by their grasp of what is known about environment-friendly products. On the contrary, choice confidence is a consumer’s certainty of which environmentally friendly products they ought to purchase. In this study, confidence refers to the extent to which consumers believe that they have adequate knowledge and choice of environmentally friendly products.\n\nShehawy and Khan (2024) disclosed that when consumers possess high knowledge and choice confidence, they are more likely to frequently buy environmentally friendly products. The degree of knowledge and choice confidence reflects how assured the consumer is that environmentally friendly products address a genuine environmental issue (Houf, Szymkowiak, & Shepherd, 2024). Due to the lack of confidence in the reliability of information about environmentally friendly products, consumers may think that environmentally friendly products are not worth purchasing (Irfany, Khairunnisa, & Tieman, 2023).\n\nPeople with high self-esteem have higher confidence in their knowledge and choices and are less affected by the views of others (Houf, Szymkowiak, & Shepherd, 2024). On the other hand, people who lack knowledge and choice confidence tend to engage in greater feedback gathering and have a lower intention to buy environmentally friendly products (Kim & Lee, 2023).\n\nThe following hypothesis is therefore evaluated in this study:\n\nThere is a positive relationship between confidence and purchase intention towards environmentally friendly products.\n\nAnother key demographic variable linked to consumers’ intention to acquire energy-related technologies is family income. Saini et al. (2024) defined family income as family income, which combines the income of all individuals living in the same household. Irfany, Khairunnisa, and Tieman (2023) highlighted that as family income increases, the disposable income will increase, and people are more likely to purchase environmentally friendly products.\n\nStranieri et al. (2023) studied the influence of family income on household energy efficiency consumption in France. The findings revealed that family income is a significant factor in the purchase of energy-efficient equipment.\n\nHouseholds with higher family incomes are more likely to care about environmental issues and thus purchase and consume more energy-related technology (Houf, Szymkowiak, & Shepherd, 2024). Households with higher incomes will consider purchasing environmentally friendly products more often (Haq et al., 2024). Therefore, if there is a higher family income, they tend to have more disposable income to buy environmentally friendly products that are more expensive than non-environmentally friendly products (Houf, Szymkowiak, & Shepherd, 2024).\n\nOn the contrary, households with lower family income could not bear the cost of environmentally friendly products, even though the equipment could eventually save their money on energy bills (Irfany, Khairunnisa, & Tieman, 2023). When it comes to making energy-efficient investments, low-income families are more cautious in spending due to financial constraints than high-income families (Shehawy & Khan, 2024).\n\nThe following hypothesis is therefore evaluated in this study:\n\nThere is a positive relationship between family income and purchase intention towards environmentally friendly products.\n\nAttitude refers to one’s assessment of positive and negative consequences of making environmentally friendly product purchases (Houf, Szymkowiak, & Shepherd, 2024). Several studies (Irfany, Khairunnisa, & Tieman, 2023; Islam & Ali Khan, 2024; Haq et al., 2024; Shehawy & Khan, 2024) have highlighted that people are more likely to engage in certain behaviors when they hold positive attitudes towards them. Consumers form positive or negative attitudes based on past information obtained from friends without actual environmentally friendly product consumption. As consumers perceive that the purchase of environmentally friendly products can alleviate the threat of climate change and possess favorable attitudes towards the behavior, they are more likely to engage in purchase behavior (Ewe & Tjiptono, 2023; Haq et al., 2024).\n\nStranieri et al. (2023) identified that consumers with a cheerful attitude towards environmentally friendly products tend to believe that their investment is beneficial, worthwhile, and gratifying. Ewe and Tjiptono (2023) found that environmental concerns have an impact on consumers’ attitudes towards environmentally friendly products. If individuals believe that environmentally friendly products can reduce carbon emissions, they are more likely to form the intention to save energy and thus engage in purchase behavior (Shehawy & Khan, 2024). Consumers with positive attitudes consider environmental issues by checking whether environmentally friendly products are ecologically compatible equipment (Houf, Szymkowiak, & Shepherd, 2024). The growing global environmental concern drives consumers to purchase environmentally friendly products (Stranieri et al., 2023). Consumers with higher environmental concerns and positive attitudes towards environmental protection are more likely to purchase environmentally friendly products (Haq et al., 2024).\n\nThe following hypothesis is therefore evaluated in this study:\n\nThere is a positive relationship between attitude and purchase intention towards environmentally friendly products.\n\nSubsidy incentives refer to government expenditure to ensure that individuals have access to environmentally friendly products (Salim et al., 2024). Ewe and Tjiptono (2023) discovered that subsidy incentives can increase the relative attractiveness of environmentally friendly products and thus promote their purchase of environmentally friendly products. Alhamad et al. (2023) investigated subsidy incentives for environmentally friendly equipment and found that the sales of environmentally friendly equipment increased drastically following subsidy incentives.\n\nOne of the strongest barriers to energy-related technologies is their high purchase prices (Haq et al., 2024). Subsidy incentives targeting environmentally friendly products can help overcome purchase costs and improve the purchase of environmentally friendly products. Alhamad et al. (2023) found that households are more likely to spend more on energy conservation items when these investments are subsidized by the government. Consumers are subsidy acceptors, and their assessment of subsidy incentives is of utmost importance for encouraging their purchase of environmentally friendly products (Houf, Szymkowiak, & Shepherd, 2024).\n\nProi et al. (2023) argue that subsidy incentives are more appealing if granted at the time of purchase. Shehawy and Khan (2024) discovered that subsidy incentives play a key role in encouraging the purchase of environment-friendly products, addressing energy security, and alleviating the adverse effects of climate change.\n\nSaini et al. (2024) discovered that citizens, particularly those above 45 years of age, are attracted to purchase environmentally friendly products when there are subsidy incentives (Gu et al., 2019). More studies need to be conducted to determine the reasons behind this finding and whether subsidy incentives are effective strategies to increase the affordability of environmentally friendly products (Proi et al., 2023).\n\nBased on the above literature, financial subsidies have a significant effect on the purchase intention for renewable energy equipment. Thus, the following hypothesis was formulated and evaluated in this study:\n\nThere is a positive relationship between subsidy incentives and purchase intention towards environmentally friendly products.\n\nThe research framework of this study is depicted in Figure 1.\n\n\n3. Method\n\nEthical clearance was obtained from the Multimedia University Ethics Committee prior to the survey (Ethical approval number: PD20220376). Written informed consent was obtained from all respondents before the start of data collection, with a written assurance of response anonymity and data confidentiality.\n\nFull ethics statement (Approved date: 3 July 2022).\n\nMMU respects your privacy and is committed to protecting your personal data. All data obtained from you will only be reported in an aggregate format. Any quotes you provide will be anonymised. All individual questionnaire responses will be concealed, and no one other than the MMU research team will have access to these. The data collected will be stored in a secure database. Data will be retained for use as a baseline reference in future evaluations. The data will not be used for any other purpose. Please contact us if you would like a copy of your survey responses, and/or if you would like us to remove your personal data from our records. Please visit our website at https://www.mmu.edu.my/privacy-notice/for further details on Privacy Notice, including how you may access and correct your personal data or withdraw consent to the collection, use or disclosure of your personal data.\n\nThe survey included six items measuring purchase intention towards environmentally friendly products, five items measuring confidence, and four items measuring family income. Furthermore, the survey also had six items measuring attitudes and four items measuring subsidy incentives. All questions in the survey were measured using 5-point Likert scales, denoted by 1: strongly disagree, 2-Disagree, 3: Neutral, 4-Agree and 5-Stongly agree.\n\nThe survey was pretested by two academics and two renewable energy experts to validate its accuracy and consistency of the survey questions (Chan et al., 2020). Based on the feedback from two academics and two renewable energy experts, amendments were made to the format, questions, and instructions to improve the survey. Thereafter, a pilot study was conducted in which surveys were distributed to 100 consumers in central Malaysia. The survey was finalized after the second round of validation by two academics and two renewable energy experts.\n\nPurposive sampling methods were used to select the respondents. For purposive sampling, respondents must have basic knowledge of environmental protection, environmentally friendly products, and be 18 years of age and above. The authors set an age limit because underage citizens may not have sufficient knowledge of climate change and environmental protection. Filtering questions such as ‘Do you know what environmentally friendly products are?’, “Are you aware of environmental protection?” and ‘Are you 18 years old and above?’ were asked face-to-face before qualified respondents were invited to complete the survey.\n\nThree hundred participants from four developed states in Malaysia had the highest awareness of environmental protection and environmentally friendly products, namely the Federal Territory of Kuala Lumpur, Selangor, Malacca, and Johor. The survey was administered to the respondents in public places. Each respondent was approached face-to-face so that accurate pre-screening could be conducted to filter unqualified respondents. The purpose of this research and the meaning of each question in the survey were clearly explained to the respondents before the start of data collection. Over a six-month period of data collection, out of three hundred participants approached, 207 agreed to participate in this research. Seven responses with incomplete or straight-line answers were excluded, and 200 valid responses were used for the analysis.\n\nDescriptive statistics were used to summarize and describe the profiles of the survey respondents. In contrast to descriptive statistics, which provide simple summaries of the profile of respondents, inferential statistics are used in this study to generalize or predict the key factors affecting environmentally friendly equipment purchase intention. Multiple linear regression analysis was used to examine the relationships between the independent and dependent variables in this study. Multiple linear regression analysis allows for the use of multiple determinants to predict purchase intention towards environmentally friendly products. It allows researchers to draw relationships about key factors affecting the purchase of environmentally friendly products based on a sample of 200 respondents, while simultaneously assessing the reliability, strength, and nature of these relationships.\n\nThe number of female respondents who participated in this study was slightly higher than the number of male respondents. There were 99 (49.5%) males and 101 (50.5%) female respondents.\n\nMost of the respondents were 21–30 years old, with a total of 90 (45%) out of 200 respondents. Next, 50 (25%) respondents were within the age group of 31 to 40 years, followed by the group of 41 to 50 years (16.5%).\n\nThere were 41 out of 200 respondents’ current family income ranging from RM3001–RM6000, which accounted for 20.5%, while 39 (19.5%) respondents’ family income ranged between RM6001 and RM9000. Most respondents had a family income of RM9001–RM12000, followed closely by RM3001–RM6000.\n\nSPSS https://www.ibm.com/products/spss-statistics?utm_content=SRCWW&p1=Search&p4=43700077631738678&p5=e&p9=58700008516329884&gclid=Cj0KCQjws560BhCuARIsAHMqE0Fc-I7aCZzUq3pVdWrwOz6Zd7BjKoe0MHxkxhimLA8wPhfDJlZ2j2IaAj7OEALw_wcB&gclsrc=aw.ds was used to measure the reliability of the survey instruments. All survey questions record high Cronbach’s Alpha values of between 0.7-0.9, as indicated by Table 1. The highest value of Cronbach’s alpha is subsidy incentives, with a value of 0.941, followed by attitude, with an alpha value of 0.940. The Cronbach’s alpha for purchase intention and family income had the same value of 0.939.\n\n\n4. Results\n\nTable 2 illustrates the consumers’ intentions to purchase environmentally friendly products. All six items measuring purchase intention towards environmentally friendly products exhibit high mean scores of above 3.500/5.000, indicating that consumers in Malaysia are aware of the importance of environmental protection and look forward to by environmentally friendly environmentally friendly products.\n\nTable 3 shows the model summary of the outcome of multiple linear regression, which was derived using SPSS https://www.ibm.com/products/spss-statistics?utm_content=SRCWW&p1=Search&p4=43700077631738678&p5=e&p9=58700008516329884&gclid=Cj0KCQjws560BhCuARIsAHMqE0Fc-I7aCZzUq3pVdWrwOz6Zd7BjKoe0MHxkxhimLA8wPhfDJlZ2j2IaAj7OEALw_wcB&gclsrc=aw.dssoftware. The R-value was 0.908, while the value of R Square was 82.5% (R2 = .825). This can be interpreted as 82.5% of the variability in the purchase intention towards environmentally friendly products being explained by three important factors: confidence, family income, and attitude.\n\nAccording to Table 3, the standardized beta coefficient of family income had the highest value of 0.460. followed by standardized beta coefficients of confidence (0.337) and attitude (0.148). The results indicate that family income is the most important predictor of purchase intention for environmentally friendly products, followed by confidence and attitude.\n\nSubsidiary incentives are found to have no relationship with the purchase intention of environmentally friendly products because the significance value is greater than 0.05, which is 0.455. Thus, it can be concluded that confidence, family income, and attitude have a significant relationship with purchase intention, whereas subsidy incentives have no significant relationship; hence, it is not accepted.\n\nTable 4 summarizes the hypothesis testing results. H1, H2, and H3 were supported, while H4 was not supported.\n\n\n5. Discussion\n\nThis study revealed a significant positive relationship between confidence and purchase intention towards environmentally friendly products. When consumers possess adequate knowledge about environmentally friendly products, an increase in confidence heightens their impact on purchase intention. Consumers with higher confidence levels have a higher probability of investing in environmentally friendly products. Moreover, this study recorded a significantly higher number of respondents with higher education compared to secondary school education, which contributes to better knowledge and thus higher confidence in environmentally friendly products.\n\nThis study also showed a significant positive relationship between family income and purchase intention towards environmentally friendly products. High-income families tend to face fewer economic constraints and are more willing to purchase environmentally friendly products. Furthermore, a higher family income has a higher opportunity to purchase environmentally friendly products, as the price of most environmentally friendly products may not be affordable due to lower family income.\n\nAnother important finding of this study is that there is a significant positive relationship between attitude toward and purchase intention towards environmentally friendly products. Customers who like the features and enjoy using environmentally friendly products are more likely to purchase environmentally friendly products. When consumers have a better attitude towards environmentally friendly products, they tend to develop purchase behavior towards them.\n\nIn contrast to Saini et al. (2024), who discovered that subsidy incentives had a significant positive impact on the purchase intention of environmentally friendly products, this study finds that there is no significant relationship between subsidy incentives and purchase intention towards environmentally friendly products. In this study, most respondents were between 21-30 years old, which indicates that most respondents were from the younger generation, who were born after 1993. The younger generations most likely have limited awareness of the subsidy incentives provided by the government to encourage consumers to purchase environmentally friendly products. This contributes to the lack of a relationship between subsidy incentives and purchase intention of environmentally friendly products in Malaysia.\n\n\nRecommendation\n\nSince the purchase and usage of environmentally friendly products in Malaysia is still prevalent, and consumers may face difficulty in evaluating the effectiveness of environmentally friendly products in preserving energy, the energy provider can propose a clear and comprehensible introduction to the effectiveness of environmentally friendly products to guide consumers to easily choose environmentally friendly products during purchase. Energy providers and related authorities could organize events or campaigns with free admissions to increase the level of awareness of the benefits of environmentally friendly products. Providers should educate consumers, particularly high-income households, that EERE products will see returns accumulate over time so that high-income households will be more willing to spend more money upfront to buy environmentally friendly products.\n\nAs this study shows that younger generations are not aware of the subsidy incentives provided by the government to support the use of environmentally friendly products, the government should formulate a better advertising strategy targeting the improvement of subsidy incentive awareness of the younger generation in Malaysia.\n\nLow-income families are less attracted to environmentally friendly products. Therefore, a specific discount or tax exemption should be provided to low-income families to improve their confidence in environmentally friendly products.\n\nWith the advancement of the Internet, social media has become one of the platforms to enhance public awareness of environmentally friendly products. More campaigns and seminars can be organized on social media to introduce the importance and advantages of environmentally friendly products to increase consumers’ confidence levels and accelerate the transformation of confidence into EERE purchasing intentions.\n\n\nConclusion and direction for future research\n\nThis study reveals three factors that significantly influence consumers’ purchase intention towards environmentally friendly products: confidence, family income, and attitude. However, no significant relationship was found between subsidy incentives and purchase intention towards environmentally friendly products. Future researchers can examine the effects of other variables, such as gender, knowledge, peer influence, and perceived usefulness, on purchase intention.\n\nIn addition, this study focused on Malaysian residents. Future research can be conducted in other countries such as Thailand, Taiwan, and Vietnam. Different countries may have different cultures and perceptions of purchase intentions for environmentally friendly products.\n\n\nEthics and consent\n\nEthical clearance was obtained from the Multimedia University Ethics Committee prior to the survey (Ethical approval number: PD20220376).\n\nWritten informed consent was obtained from all respondents before the start of data collection, with a written assurance of response anonymity and data confidentiality.\n\nFull ethics statement (Approved date: 3 July 2022).\n\nMMU respects your privacy and is committed to protecting your personal data. All data obtained from you will only be reported in an aggregate format. Any quotes you provide will be anonymised. All individual questionnaire responses will be concealed, and no one other than the MMU research team will have access to these. The data collected will be stored in a secure database. Data will be retained for use as a baseline reference in future evaluations. The data will not be used for any other purpose. Please contact us if you would like a copy of your survey responses, and/or if you would like us to remove your personal data from our records. Please visit our website at https://www.mmu.edu.my/privacy-notice/for further details on Privacy Notice, including how you may access and correct your personal data or withdraw consent to the collection, use or disclosure of your personal data.",
"appendix": "Data availability\n\nFigshare: Yee Yen, Yuen (2024). A Survey Measuring Purchase Intention towards Environmentally Friendly Products. figshare. Dataset. https://doi.org/10.6084/m9.figshare.26132902 (Yuen, 2024).\n\nThis project contains the following underlying data:\n\n• Data.xlsx\n\nFigshare: Yee Yen, Yuen (2024). A Survey Measuring Purchase Intention towards Environmentally Friendly Products. figshare. Dataset. https://doi.org/10.6084/m9.figshare.26132902 (Yuen, 2024).\n\nThis project contains the following extended data:\n\n• Questionnaire.docx\n\nThe data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAbd Aziz AJ, Baharuddin NA, Khalid RM, et al.: Review of the policies and development programs for renewable energy in Malaysia: Progress, achievements, and challenges. Energy Explor. Exploit. 2024; 42: 1472–1501. Publisher Full Text\n\nAlhamad AM, Jaafar ZM, Salem AM: Influence of consumer environmental responsibility on green consumption intention in Iraqi universities: The role of purchase convenience and availability of green products. Int. J. Eng. Sci. 2023; 13(7): 41–49.\n\nAsif MH, Zhongfu T, Irfan M, et al.: Do environmental knowledge and green trust matter for purchase intention of eco-friendly home appliances? An application of extended theory of planned behavior. Environ. Sci. Pollut. Res. 2023; 30(13): 37762–37774. PubMed Abstract | Publisher Full Text\n\nChan TM, Sebok-Syer SS, Sampson C, et al.: The Quality of Assessment of Learning (Qual) score: validity evidence for a scoring system aimed at rating short, workplace-based comments on trainee performance. Teach. Learn. Med. 2020; 32(3): 319–329. PubMed Abstract | Publisher Full Text\n\nEwe SY, Tjiptono F: Green behavior among Gen Z consumers in an emerging market: eco-friendly versus non-eco-friendly products. Young Consum. 2023; 24(2): 234–252. Publisher Full Text\n\nGu S, Wang F, Patel NP, et al.: A model for basic emotions using observations of behavior in Drosophila.Front. Psychol.2019; 10(1): Article 781. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHaq MRI, Nurhaliza DV, Rahmat LN, et al.: The influence of environmentally friendly packaging on consumer interest in implementing zero waste in the food industry to meet sustainable development goals (SDGs) needs. ASEAN J. Econ. Econ. Educ. 2024; 3(2): 111–116.\n\nHouf L, Szymkowiak A, Shepherd LA: Promotion of Sustainable Products: Can Sustainability Labels Promote User Selection of Environmentally Friendly Products? Sustainability. 2024; 16(13): 5390. Publisher Full Text\n\nHung CZ, Chang TW: Have I purchased the right product? Consumer behavior under corporate greenwash behavior. J. Consum. Behav. 2024; 23(3): 1102–1113. Publisher Full Text\n\nIrfany MI, Khairunnisa Y, Tieman M: Factors influencing Muslim Generation Z consumers’ purchase intention of environmentally friendly halal cosmetic products. J. Islam. Mark. 2023; 15(1): 221–243. Publisher Full Text\n\nIslam Q, Ali Khan SMF: Assessing consumer behavior in sustainable product markets: A structural equation modeling approach with partial least squares analysis. Sustainability. 2024; 16(8): 3400. Publisher Full Text\n\nKim N, Lee K: Environmental consciousness, purchase intention, and actual purchase behavior of eco-friendly products: the moderating impact of situational context. Int. J. Environ. Res. Public Health. 2023; 20(7): 5312. PubMed Abstract | Publisher Full Text | Free Full Text\n\nProi M, Dudinskaya EC, Naspetti S, et al.: The role of eco-labels in making environmentally friendly choices: an eye-tracking study on aquaculture products with Italian consumers. Sustainability. 2023; 15(5): 4659. Publisher Full Text\n\nReddy KP, Chandu V, Srilakshmi S, et al.: Consumers perception on green marketing towards eco-friendly fast moving consumer goods. Int. J. Eng. Bus. Manage. 2023; 15: 18479790231170962. Publisher Full Text\n\nSaini A, Kumar A, Mishra SK, et al.: Do environment-friendly toys have a future? An empirical assessment of buyers’ green toys decision-making. Environ. Dev. Sustain. 2024; 26(3): 5869–5889. Publisher Full Text\n\nSalim MN, Abd Rahman NH, Susilastuti D, et al.: Application of MSME and green economy principles for sustainability in Indonesia and Malaysia. Tec. Empresarial. 2024; 19(1): 146–159. Publisher Full Text\n\nShehawy YM, Khan SMFA: Consumer readiness for green consumption: The role of green awareness as a moderator of the relationship between green attitudes and purchase intentions. J. Retail. Consum. Serv. 2024; 78(1): 103739. Publisher Full Text\n\nStranieri S, Ricci EC, Stiletto A, et al.: How about choosing environmentally friendly beef? Exploring purchase intentions among Italian consumers. Renew. Agr. Food Syst. 2023; 38(1): e2. Publisher Full Text\n\nYuen YY: A Survey Measuring Purchase Intention towards Environmentally Friendly Products. figshare. [Dataset]. 2024. Publisher Full Text"
}
|
[
{
"id": "318648",
"date": "04 Oct 2024",
"name": "Akram M. Alhamad",
"expertise": [
"Reviewer Expertise Marketing",
"Green Marketing",
"Consumers’ Purchasing Intention",
"green Purchasing Intention",
"and green product."
],
"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 of the Article: 1. The work is presented and cites some current literature; there are areas where it could provide a more comprehensive review of the latest research. Although relevant sources are included, there are gaps in fully integrating more recent or diverse studies that would enhance the depth of the literature review. 2. The study does not provide granular details regarding the operationalization of variables, such as the specific survey items or scales used to measure constructs like \"confidence\" and \"attitude.\" Additionally, key methodological steps—such as the exact procedures for respondent selection and the conditions under which the survey was administered—are not fully explained. Without this level of specificity, future researchers would face significant challenges in replicating the study, potentially leading to variations in results and undermining the reliability and validity of comparative findings. For true scientific rigor, replication requires a broad description of the methods and precise details that ensure consistency across different research implementations. 3. The statistical analysis appears appropriate with multiple linear regression; key assumptions, such as normality, multicollinearity, and homoscedasticity, are not fully addressed in the report. Without confirming these assumptions, the robustness of the analysis may be compromised, and the interpretation could be affected by potential biases in the model. Therefore, while the methods used are generally suitable, further checks on statistical assumptions would be necessary for a more confident interpretation. 4. The conclusions would not be adequately supported if they overgeneralize the findings beyond the data's scope or make claims not directly tested by the analysis. For instance, if the study concluded broader implications for global consumer behavior based solely on a sample from Malaysia without comparative data, this would undermine the validity of the conclusions. Additionally, if the study failed to address limitations or alternative explanations for the findings, the conclusions would lack academic rigor, as they would not fully reflect the complexities of the data and the potential variability in real-world applications. Sound conclusions must directly stem from the data while acknowledging the study's limitations and the broader context of the research field.\nSuggestions for Improvement:\nExpand the Literature Review: The authors should include more recent studies to enhance the relevance of the work. Expanding the geographical context of the literature review to include other developing countries would provide a more comprehensive understanding of the global challenges related to environmentally friendly product purchases. Address Statistical Assumptions: The article should explicitly state whether key assumptions of multiple linear regression (normality, multicollinearity, homoscedasticity) were checked. If not, this is a critical area that must be addressed to ensure robust statistical analysis. Including tests for these assumptions in the analysis section and discussing their outcomes will strengthen the reliability of the findings. Report Effect Sizes and Confidence Intervals: While the article includes statistical significance (p-values), it does not provide effect sizes or confidence intervals. Including these metrics would give a more nuanced understanding of the results and their practical significance, making the findings more informative for future research and policy recommendations.\nPoints That Must Be Addressed to Make the Article Scientifically Sound:\nChecking and reporting key assumptions of the multiple linear regression model is essential for ensuring the statistical validity of the analysis. This step must be included to make the article scientifically sound. Including more recent and geographically diverse literature in the review is important for strengthening the contextual relevance 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? 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?\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": "345528",
"date": "09 Jan 2025",
"name": "Suhail M. Ghouse",
"expertise": [
"Reviewer Expertise Marketing and Entrepreneurship"
],
"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\nSummary of the Article The article, \"A survey measuring purchase intention towards environmentally friendly products,\" by Yuen Yee Yen and Tan Zi Ling, investigates factors influencing Malaysian consumers' purchase intentions for environmentally friendly products. Using a survey of 200 respondents, the study identifies confidence, family income, and attitude as significant predictors of purchase intention, while subsidy incentives showed no significant impact. The findings offer practical recommendations for policymakers and marketers to promote environmentally friendly products and highlight areas for future research. Evaluation of the Article 1. Is the work clearly and accurately presented, and does it cite the current literature? Answer: Partly\nStrengths: The article is well-structured, with a logical flow and clarity in presenting its objectives, methodology, and results. It incorporates relevant references to contextualize its findings within the Malaysian landscape. Weaknesses: The literature review is not comprehensive, lacking insights from recent and globally diverse studies on environmentally friendly product purchases.\nRecommendations: Expand the literature review by including more recent and geographically diverse studies to strengthen the paper's theoretical foundation. For example:\nPeattie, K. (2010 [Ref-1]). Green consumption: behavior and norms. Annual Review of Environment and Resources, 35(1), 195-228. This reference can provide foundational insights into green consumption behavior and norms. Ghouse, S. M., Shekhar, R., & Chaudhary, M. (2024 [Ref-2]). Sustainable choices of Gen Y and Gen Z: exploring green horizons. Management & Sustainability: An Arab Review. This study can offer perspectives on generational differences in sustainable choices. Sarmad, I., Bukhari, S. M. H., & Hafeez, S. (2024 [Ref-3]). Consumer Responses to Eco-Friendly Product Claims: The Role of Information Asymmetry and Online Reviews. This reference explores confidence in eco-friendly products, a core construct in this study.\n\n2. Is the study design appropriate and is the work technically sound? Answer: Partly\nStrengths: The study employs multiple linear regression to analyze the relationships between variables, which is an appropriate method. The use of pretests and pilot studies ensures that the survey instrument is reliable. Weaknesses: The sampling method (purposive sampling) limits the generalizability of findings, and the paper does not provide sufficient details on statistical assumptions (e.g., normality, multicollinearity, homoscedasticity).\nRecommendations:\nJustify the use of purposive sampling by discussing its relevance and limitations. For example, explain how the method aligns with the study's objectives despite limiting generalizability. Address statistical assumptions explicitly by reporting tests for normality, multicollinearity, and homoscedasticity. This will strengthen the robustness of the analysis.\n\n3. Are sufficient details of methods and analysis provided to allow replication by others?\nAnswer: Partly Strengths: The methodology includes descriptions of the survey instrument, pretesting, and pilot studies, providing a basis for replication. Weaknesses: The operational definitions of variables and the exact survey items are not detailed. The conditions under which the survey was conducted are also not explained.\nRecommendations:\nInclude the exact survey items and scales in the paper (e.g., as a supplementary table or appendix). For instance:\nAdd constructs from Ghouse, S. M., Shekhar, R., Ali Sulaiman, M. A. B., & Azam, A. (2024 [Ref-4]). Green purchase behaviour of Arab millennials towards eco-friendly products: the moderating role of eco-labelling.\n\nProvide details on survey administration, including the environment, timing, and how participants were approached.\n\n4. If applicable, is the statistical analysis and its interpretation appropriate?\nAnswer: Partly Strengths: The use of multiple linear regression is suitable for testing the hypotheses. The study reports standardized beta coefficients and p-values for the analysis. Weaknesses: Effect sizes and confidence intervals are not reported, limiting the understanding of the practical significance of the findings. Statistical assumptions are not addressed.\nRecommendations:\nReport effect sizes and confidence intervals for all predictors to provide a clearer understanding of their impact. Include tests for statistical assumptions such as:\nMulticollinearity (e.g., using Variance Inflation Factor). Normality (e.g., using the Shapiro-Wilk test). Homoscedasticity (e.g., via a Breusch-Pagan test).\n\n5. Are all the source data underlying the results available to ensure full reproducibility?\nAnswer: Yes Strengths: The study provides access to the dataset and survey instruments via a public repository, ensuring transparency and reproducibility.\n\n6. Are the conclusions drawn adequately supported by the results?\nAnswer: Partly Strengths: The conclusions align with the results, emphasizing the significance of confidence, family income, and attitude in influencing purchase intention. Weaknesses: The discussion on non-significant findings (subsidy incentives) is insufficient. The study overgeneralizes its conclusions without acknowledging the limitations of the sampling method.\nRecommendations:\nProvide a detailed discussion of the non-significant finding for subsidy incentives. For example: Consider demographic factors such as generational awareness of subsidies. Reference Ali, M., Ullah, S., Ahmad, M. S., Cheok, M. Y., & Alenezi, H. (2023 [Ref-5]). Assessing the impact of green consumption behavior and green purchase intention among millennials toward sustainable environment. Highlight limitations, including geographic and sampling constraints, and caution against overgeneralizing the findings.\n\nAdditional References for Integration\nPeattie, K. (2010[Ref-1]). Green consumption: behavior and norms. Annual Review of Environment and Resources, 35(1), 195-228. Ghouse, S. M., Shekhar, R., Ali Sulaiman, M. A. B., & Azam, A. (2024 [Ref-4]). Green purchase behaviour of Arab millennials towards eco-friendly products: the moderating role of eco-labelling. Ghouse, S. M., Shekhar, R., & Chaudhary, M. (2024 [Ref-2]). Sustainable choices of Gen Y and Gen Z: exploring green horizons. Sarmad, I., Bukhari, S. M. H., & Hafeez, S. (2024[Ref-3]). Consumer Responses to Eco-Friendly Product Claims: The Role of Information Asymmetry and Online Reviews. Ali, M., Ullah, S., Ahmad, M. S., Cheok, M. Y., & Alenezi, H. (2023 [Ref-5]). Assessing the impact of green consumption behavior and green purchase intention among millennials toward sustainable environment. Varshneya, G., Pandey, S. K., & Das, G. (2017 [Ref-6]). Impact of social influence and green consumption values on purchase intention of organic clothing: a study on collectivist developing economy.\nConclusion The article provides valuable insights into factors influencing environmentally friendly product purchases in Malaysia. However, addressing the outlined gaps—expanding the literature review, providing greater methodological detail, and improving statistical reporting—will significantly enhance its scientific rigor and practical relevance. These improvements are necessary to make the article more robust and impactful for publication and indexing.\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": []
}
] | 1
|
https://f1000research.com/articles/13-938
|
https://f1000research.com/articles/13-937/v1
|
20 Aug 24
|
{
"type": "Research Article",
"title": "Comprehensive Analysis of Demographic, Clinical, and Genetic Characteristics in Acute Myocardial Infarction Patients",
"authors": [
"Ngoc-Nga Pham-Thi",
"Thu-Lan Tran-Thi",
"Hong-Quan Duong",
"Hoang-Long Do",
"Trung-Cang Huynh",
"Trung-Son Le",
"Tan-Khang Do",
"Ngoc-Nga Pham-Thi",
"Thu-Lan Tran-Thi",
"Hong-Quan Duong",
"Hoang-Long Do",
"Trung-Son Le",
"Tan-Khang Do"
],
"abstract": "Background Coronary artery disease (CAD) and acute myocardial infarction (AMI) are substantial contributors to the global disease burden and mortality. The ANRIL gene polymorphism rs1333040 has been implicated in susceptibility to cardiovascular disease; however, its role in the Vietnamese population remains unclear.\n\nMethods A cross-sectional study was conducted on 185 Vietnamese patients diagnosed with acute coronary syndrome (ACS), and clinical data, medical history, and biochemical parameters were recorded. ANRIL SNP rs1333040 was genotyped using PCR-RFLP. Genotype frequencies were assessed for Hardy-Weinberg equilibrium and their association with cardiovascular risk factors.\n\nResults The ‘Normal’ BMI (Body Mass Index) category was the largest segment, comprising 77.84% of the sample. Key cardiovascular risk factors identified among patients with AMI included hypertension (83.8%), dyslipidemia (80.0%), smoking (50.0%), and diabetes mellitus (33.8%). Clinical presentation showed that 55.0% of patients had non-ST-elevation myocardial infarction (NSTEMI) and 45.0% had ST-elevation myocardial infarction (STEMI). Lipid profile abnormalities were significant; 60.0% had decreased High-Density Lipoprotein Cholesterol (HDL-C), 53.8% had elevated triglycerides, 37.5% had elevated Low-Density Lipoprotein Cholesterol (LDL-C), and 36.3% had elevated total cholesterol levels. Genetic analysis focused on the rs1333040 polymorphism of the ANRIL gene, with the most common genotype being TT (58.8%), followed by CT (33.7%) and CC (7.5%). Allele frequencies were 75.6% for T and 24.4% for C. This study is the clinical implications of ANRIL polymorphisms in Vietnamese patients with CAD and AMI. Significant genotype-phenotype associations were observed, underscoring the importance of incorporating genetic screening for enhanced prognostic capabilities and personalized therapeutic decisions. Further research focused on delineating the precise genetic underpinnings of complex cardiovascular diseases in diverse populations is warranted.",
"keywords": [
"ANRIL",
"polymorphism",
"acute myocardial infarction",
"coronary artery disease",
"genotype-phenotype correlation"
],
"content": "Introduction\n\nCoronary artery disease (CAD) involves restricted blood flow in the coronary arteries, typically due to atheroma buildup (Byrne et al., 2015; Lawton Jennifer et al., 2022). Manifestations range from silent ischemia to angina, acute coronary syndrome (ACS) such as myocardial infarction, and sudden cardiac death (Lawton Jennifer et al., 2022). The diagnosis uses symptoms, electrocardiography (ECG), stress tests, and angiography. Prevention targets modifiable risks such as hypertension, diabetes, obesity, and smoking (Lawton Jennifer et al., 2022; O’Gara et al., 2013). Treatment includes medication and revascularization procedures (O’Gara et al., 2013; Stone et al., 2014). In high-income countries, CAD causes approximately one-third of all deaths, making it the leading cause of mortality for both genders (Lawton Jennifer et al., 2022). Among white men, mortality increases from approximately 1 in 10,000 at ages 25-34 years to nearly 1 in 100 at 55-64 years. Mortality rates are over six times higher in men than in women aged 35-44 years, but this gap narrows in older individuals and those with diabetes (Lawton Jennifer et al., 2022).\n\nAcute MI involves abrupt cessation of myocardial blood supply due to coronary artery occlusion, linked historically to thrombus formation evident in 19th-century autopsies (Thygesen et al., 2018). By the early 20th century, coronary thromboses were connected to associated MI features, despite initial doubts from postmortem studies showing a lack of thrombi in many cases (Thygesen et al., 2018). Multiple MI definitions created confusion until ECG-based criteria were established in the 1950s-1970s–epidemiology (Thygesen et al., 2018). Despite its prognostic benefits, MI remains the primary cause of illness and death globally (Reed et al., 2017). Improved risk assessment, revascularization, and preventative measures such as statins have contributed to this progress. However, over half of cardiac troponin elevations occur without acute thrombotic causes, necessitating research on type 2 MI management (Chapman et al., 2020).\n\nThe ANRIL gene (CDKN2B-AS1) on chromosome 9p21 interacts with polycomb complexes and epigenetically regulates neighboring genes. This locus is a key genetic susceptibility point for cardiovascular diseases and conditions such as diabetes, cancer, aneurysm, and Alzheimer’s disease (PMID:21151960). Investigating ANRIL is crucial for elucidating their pivotal role in various diseases. Non-coding RNAs (ncRNAs) regulate gene expression without encoding proteins (Ferreira & Esteller, 2018). The ANRIL ncRNA at 9p21 has been repeatedly linked to atherosclerosis and related ischemic heart disease (Congrains et al., 2012; Cunnington & Keavney, 2011). Although its function remains unclear, ANRIL affects the expression of adjoining genes such as CDKN2A/B (Cyclin-Dependent Kinase Inhibitor 2A/B) and Methylthioadenosine Phosphorylase (MTAP), which are involved in vascular remodelling and thrombogenesis (Congrains et al., 2012). Thus, ANRIL polymorphisms may influence atherosclerotic CAD. While some early studies suggest correlations between ANRIL variants and CAD risk, the results are conflicting (Congrains et al., 2012; Cunnington & Keavney, 2011; Holdt & Teupser, 2018). Further research on ANRIL genotypes in myocardial infarction is urgently warranted.\n\nThis study analyzed the association between ANRIL rs1333040 and clinical manifestations in Vietnamese patients with CAD, particularly in those with acute MI. This study aimed to elucidate the link between this variant and symptom severity in order to reveal the role of ANRIL genotypes in the presentation of acute myocardial infarction (AMI) in patients with CAD in Vietnam. This study aimed to elucidate the genetic underpinnings of AMI in this population.\n\n\nMethods\n\nThis study included 185 patients diagnosed with and treated for ACS at the Hoan My Cuu Long General Hospital from May 2023 to October 2023. The selection criteria were patients diagnosed with ACS, including both non-ST-elevation myocardial infarction and ST-elevation myocardial infarction, according to the ACC/AHA/SCAI Guidelines for Coronary Artery Revascularization (Lawton Jennifer et al., 2022; O’Gara et al., 2013). Those who willingly participated in the study were included. Patients with terminal cancer, comatose states, or secondary ACS were excluded. This study adopted a descriptive cross-sectional approach to provide a snapshot of the patient population during a specified period to elucidate the associations between genetic variations and clinical symptoms in ACS.\n\nThe study involved Blood samples were collected from 185 patients (aged 40–95 years) who were diagnosed with acute myocardial infarction. At the time of blood collection, comprehensive clinical information, including risk factors associated with acute myocardial infarction (AMI) such as sex, age, history of hypertension, triglyceride levels, and history of diabetes, was gathered (Golabgir Khademi et al., 2016). Hypertension was defined as a systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mm Hg (Golabgir Khademi et al., 2016). These risk factors were determined based on physician diagnosis, medical records, and biochemical tests (Golabgir Khademi et al., 2016). This study employed internationally standardized methods for sample collection. Blood samples were analyzed for various parameters, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). These biochemical markers were assessed to provide comprehensive insight into the biochemical profiles associated with AMI (Huang et al., 2018). Diabetes was identified through ongoing diabetes treatment or fasting blood sugar levels > 126 mg/dL. Elevated triglyceride levels were defined as fasting triglyceride levels of > 150 mg/dL (Golabgir Khademi et al., 2016).\n\nHuman genomic DNA was extracted from the blood samples using the QiAmp DNA Mini Kit (Qiagen, Hilden, Germany). Genotyping of the investigated SNPs (rs1333040) was performed using PCR and restriction fragment length polymorphism (RFLP). The studied SNPs were 32185 nucleotides away from each other and were amplified. The oligonucleotide primers rs1333040F (5’-AAGAAGGCTGGTAGCAGGAAG-3’) and rs1333040R (5’- ATCACCACCCAAACACCAGT-3’) (Golabgir Khademi et al., 2016).\n\nThe PCR reaction was carried out in a final reaction volume of 50 μL using 3 μL genomic DNA as a template. The reaction mixture (rs1333040) contained 2 μL of each primer (10 μM), 25 μL of MyTaq Mix (2x) (Meridian Life Science Inc., USA), and 18 μL of water (ddH2O) (Golabgir Khademi et al., 2016; Hoang Ngo et al., 2023; Le et al., 2021).\n\nThe cycling program was as follows: initial denaturation at 95 °C for 5 min followed by 35 cycles of denaturation at 95 °C for 30 s, annealing at 68 °C for 30 s, and extension at 72 °C for 60 s. The amplification was terminated after 5 min of extension at 72 °C. The size of the PCR product for the rs1333040 polymorphism is 900 bp (Golabgir Khademi et al., 2016).\n\nThe PCR products of SNP were digested with the restriction endonuclease BsmI (Thermo, Mỹ) for rs1333040 (Golabgir Khademi et al., 2016). The digested products were detected by agarose gel electrophoresis.\n\nAll data were entered and analyzed using R statistical software. Genotype and allele frequencies of the rs1333040 polymorphism were determined. Hardy-Weinberg equilibrium was tested using the chi-square test to compare the observed and expected genotype distributions (Rohlfs & Weir, 2008; Woldu et al., 2022).\n\nClinical characteristics and biochemical parameters between the different genotype groups were compared using the chi-square test. The association between rs1333040 genotype and disease risk was evaluated using multivariate logistic regression analysis. Statistical significance was set at P < 0.05.\n\n\nResults\n\nThe age distribution of the patients was analyzed according to their sex. For female patients, age ranged from 54 to 89 years, with the first quartile (25th percentile) at approximately 64 years, median (50th percentile) at 67 years, mean (average) age at 68.85 years, and third quartile (75th percentile) at approximately 74 years. In contrast, male patients had ages ranging from 44 to 93 years, with the first quartile at 54 years, the median at 54.5 years, the mean age at 63.58 years, and the third quartile at approximately 70 years. This indicates a slightly higher median and mean age for female patients (67 and 68.85 years, respectively) than for male patients (54.5 and 63.58 years, respectively). The age range was broader for male patients (44–93 years) than for female patients (54–89 years), indicating greater age variability among males (Figure 1).\n\nWithin the dataset, Body Mass Index (BMI) distribution highlighted the prevalence of various weight statuses. The BMI categories were thin (<18.5), normal (18.5-25), Overweight (25-30), and obese (>30), providing insights into the population’s weight classifications (Figure 2). The ‘Thinness’ category comprises 4.86% of the population (9 cases) with a BMI below 18.5. The median age of this group was 82 years, with ages ranging from 71 to 93 years, indicating a tendency of older individuals to be classified as underweight. The ‘Normal’ category, being the largest segment, includes 77.84% of the sample (144 cases) with BMIs between 18.5 and 25. The age distribution within this category ranged from 48 to 89 years, with a median age of 65 years, reflecting a diverse age range within the healthy weight category. The overweight category accounted for 15.14% of the population (28 cases), with BMIs between 25 and 30. The median age is 58 years, with ages ranging from 54 to 92 years, showing a wider age range compared to the ‘Normal’ BMI category. Finally, the ‘Obese’ category, comprising 2.16% of the cases (4 individuals), includes those with a BMI over 30. The median age of patients in this group was 64 years.\n\nOverall, the data demonstrates age and BMI distributions across the patient population, with notable differences in age distribution by gender and significant representation within the ‘Normal’ BMI category. This analysis provides a comprehensive overview of the demographic characteristics of the study population, highlighting age and BMI variations across different groups.\n\nCardiovascular Risk Factors - The study identified several key cardiovascular risk factors among patients with AMI. Hypertension was the most prevalent condition, affecting 83.8% of the patients. Dyslipidemia was also highly prevalent (80.0%). Diabetes mellitus was present in 33.8% of the patients, while 50.0% were smokers. Notably, 13.8% of the patients were overweight or obese, and a small percentage (2.5%) had a family history of cardiovascular disease (Table 1).\n\nThe Killip classification, which is crucial for prognosis, showed that the majority of patients (93.8%) were in Killip class I. Only 2.5% were in class II and 3.8% were in classes III-IV, indicating more severe heart failure symptoms (Table 1).\n\nClinical Presentation: In terms of clinical presentation, 55.0% of patients had non-ST-elevation myocardial infarction (NSTEMI) and 45.0% had ST-elevation myocardial infarction (STEMI) (Table 1).\n\nElectrocardiogram (ECG) Findings - ECG findings revealed that 43.8% of patients had ST elevation, 45.0% had ST depression, 38.8% had T-wave abnormalities, and 36.3% had pathological Q waves. These findings are critical for diagnosing and determining AMI severity (Table 1).\n\nLipid profile analysis showed that 60.0% of the patients had decreased HDL-C levels, 53.8% had elevated triglycerides, 37.5% had elevated LDL-C, and 36.3% had elevated total cholesterol. These abnormalities are significant risk factors for cardiovascular diseases (Table 1).\n\nEjection Fraction (EF) - Echocardiographic data indicated that 78.7% of the patients had preserved EF, 11.3% had mildly reduced EF, and 10.0% had reduced EF. The preserved EF in the majority of patients suggests that the left ventricular systolic function was maintained in many cases (Table 1).\n\nMean hs-Troponin I Level - The mean hs-troponin I level was significantly higher in STEMI patients (16,292.54 ng/L) compared to NSTEMI patients (3,445.16 ng/L), reflecting the more extensive myocardial damage typically seen in STEMI (Table 2).\n\nThis study highlights the high prevalence of traditional cardiovascular risk factors among patients with AMI, with hypertension and dyslipidemia being the most common risk factors. The Killip classification and ECG findings underscore the severity and clinical presentation of AMI. Lipid abnormalities are prevalent and contribute to the risk profile of these patients. Ejection fraction data provide insight into the cardiac function of the patient population, while hs-troponin I levels differentiate between STEMI and NSTEMI, aiding in the stratification of patient risk and management strategies.\n\nThree different genotypes were identified using the PCR-RFLP method and were subsequently confirmed by genetic sequencing using a Beckman Coulter CEQ8000 sequencer. The products were sequenced using an ABI 3500 sequencer and analyzed using SeqScape v2.7 software. Hardy-Weinberg equilibrium testing was applied to validate the independent segregation of the C and T alleles within the study population. The calculated chi-square value was χ2 = 0.57 with p = 0.45, indicating that the AMI patient population in the study adhered to Hardy-Weinberg equilibrium.\n\nDistribution of the rs1333040 polymorphism revealed the following genotype frequencies: Wild-type genotype TT was the most prevalent, accounting for 58.8% (n = 47) of the samples. The heterozygous genotype CT was found in 33.7% (n = 27) of the samples, whereas the homozygous CC genotype had the lowest frequency at 7.5% (n = 6) (Table 3).\n\nWhen comparing allele frequencies, the T allele was more common (n = 121, 75.6%) compared to the C allele (n = 39, 24.4%). In the dominant model analysis (TT + CT), the combined frequency was 92.5%, whereas it was 41.2% in recessive model analysis (CC + CT). The results are presented in Table 3 presents the results.\n\nThese results provided a comprehensive overview of the genotype and allele distributions within the study population, reflecting the genetic diversity related to the rs1333040 polymorphism in patients with AMI (Table 3).\n\nThis study investigated the association between ANRIL rs1333040 polymorphism and various biochemical blood parameters in patients with AMI. Using weighted mean analysis and standard deviation (SD) calculations followed by ANOVA, we examined glucose, total cholesterol, serum LDL-C, HDL-C, and triglycerides. Despite the observed differences in mean values across genotypes (TT, CT, and CC).\n\nThe mean and standard deviation (mean ± SD) for each biochemical parameter across the three genotypes are presented in Table 4. For glucose, the mean values were 119.7 ± 33.4 mg/dL for the CC genotype, 118.9 ± 32.8 mg/dL for the CT genotype, and 124.1 ± 41.6 mg/dL for the TT genotype. Total cholesterol levels were 169.5 ± 74.1 mg/dL for the CC genotype, 214.7 ± 193.6 mg/dL for the CT genotype, and 186.8 ± 65.6 mg/dL for the TT genotype. HDL-C levels were 39.9 ± 13.1 mg/dL for the CC genotype, 43 ± 28.3 mg/dL for the CT genotype, and 49.5 ± 48.6 mg/dL for the TT genotype. LDL-C levels were 101.3 ± 48.5 mg/dL for the CC genotype, 118 ± 48.9 mg/dL for the CT genotype, and 122.8 ± 54.8 mg/dL for the TT genotype. Triglycerides levels were 201.2 ± 108 mg/dL for the CC genotype, 158.8 ± 119.4 mg/dL for the CT genotype, and 193.7 ± 117.7 mg/dL for the TT genotype. Although there were variations in the mean values of these biochemical parameters among the different genotypes, ANOVA indicated no significant associations (p > 0.05) for any of the parameters examined.\n\nOur analysis did not reveal any significant association between the rs1333040 polymorphism of ANRIL and the measured biochemical parameters (Table 4). The highest mean glucose level was found in the TT genotype group (124.1 ± 41.6 mg/dL), while the CT genotype group had the highest mean total cholesterol (214.7 ± 193.6 mg/dL). The CC genotype group had the lowest mean HDL-C (39.9 ± 13.1 mg/dL). Despite these differences, none were statistically significant, highlighting the need for further studies with larger sample sizes to confirm our findings.\n\n\nDiscussion\n\nThe study observed a mean age of 66.8±10.47 years among participants, consistent with previous research. Ding (2009) reported a mean age of 63.8±10.6 years in Chinese Han patients with coronary artery disease (Ding et al., 2009). Similarly, Lin’s study on Taiwanese AMI patients reported a mean age of 63.2±13.1 years, and Dong-Ling Huang (2018) found an average age of 61.63±10.65 years in AMI patients (Huang et al., 2018; Lina et al., 2008). These findings are consistent with the pathophysiology of ageing, arteriosclerosis, and atherosclerosis. Regarding sex, the study revealed a male predominance (58.8%), which mirrors the findings of Dong-Ling Huang (77.2% males among 334 AMI patients) (Huang et al., 2018). This higher prevalence in males may be attributed to risk factors, such as smoking, alcohol consumption, and work-related stress.\n\nThese demographic characteristics align with the global and domestic epidemiological data on cardiovascular and metabolic diseases, indicating a higher incidence in older males. The study found that the majority of patients with AMI were classified as Killip class I (93.8%), with smaller percentages classified as Killip class II (2.5%) and Killip class III-IV (3.8%). Similarly, Abdul Ghaffar Memon reported Killip I in 76% of 150 AMI patients (Memon & Khan, 2017). The Killip classification is crucial for assessing in-hospital mortality risk and treatment benefits, and serves as an independent predictor of long-term mortality in AMI patients (Mello et al., 2014).\n\nThese findings indicate a higher prevalence of non-ST-elevation myocardial infarction (NSTEMI) (55%) than ST-elevation myocardial infarction (STEMI), consistent with the findings of Gao et al. (2008) (43% STEMI, 57% NSTEMI) and Lina et al. (2008) (27.5% STEMI, 67.8% NSTEMI) (Gao et al., 2008; Lina et al., 2008). STEMI is typically associated with large coronary artery thrombosis and higher mortality rates than NSTEMI. Differentiating STEMI from NSTEMI is critical, as fibrinolytic therapy benefits STEMI patients but may increase their risk in NSTEMI patients, and emergency interventions are prioritized for acute STEMI cases. The study reported 43.8% STEMI and 45.3% NSTEMI cases, with 38.8% showing T-wave abnormalities and 36.3% presenting with pathological Q-waves. ECG remains the primary diagnostic tool for coronary artery disease because of its simplicity, cost-effectiveness, and widespread availability. The average hs-Troponin I levels were higher in patients (16,292.54 ng/L) than in NSTEMI patients (3,445.16 ng/L). Elevated troponin I levels are indicative of greater myocardial damage and a poorer prognosis. Troponin I has been established as a specific marker for myocardial injury and predictor of cardiovascular events since 1992 (Thygesen et al., 2018).\n\nThe study confirmed the Hardy-Weinberg equilibrium for SNP rs1333040 with χ2 = 0.57 and p = 0.45. The TT genotype was the most prevalent (58.8%), followed by CT (33.7%) and CC (7.5%). These results are consistent with global studies (Congrains et al., 2012; Huang et al., 2018; Qi et al., 2012). These differences may arise from racial, geographic, and sample size variations. Analysis showed that Allele T was predominant (75.6%), whereas allele C accounted for 24.4%. These frequencies are consistent with those reported by Khademi et al. (2016), Huang (2018), and Temel and Ergören (2019).\n\nThe study found that 83.8% of AMI patients had hypertension (HTN). However, no significant association was found between the rs1333040 genotype and HTN (p > 0.05), which is consistent with the studies by Khademi et al. (2016) and Lina et al. (2008), but in contrast to Huang et al. (2018), who found a significant association in the Chinese Han population (Golabgir Khademi et al., 2016; Huang et al., 2018; Lina et al., 2008). HTN remains a major cardiovascular risk factor that promotes atherosclerosis and significantly increases the risk of coronary artery disease (Williams et al., 2018).\n\nThe study reported a dyslipidemia prevalence of 80.0%, with HDL-C reduction being the most common abnormality (60.0%). No significant association was found between SNP rs1333040 and lipid abnormalities (p > 0.05), similar to the findings of Lina’s and Huang’s findings (Huang et al., 2018; Lina et al., 2008). Dyslipidemia, characterized by elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides and reduced high-density lipoprotein cholesterol (HDL-C) levels, significantly contributes to atherosclerosis and cardiovascular diseases.\n\nThis study provides valuable insights into the demographic, clinical, and genetic characteristics of patients with AMI, highlighting significant findings and confirming the relevance of the existing research. Genetic analysis of SNP rs1333040, although not showing significant associations with HTN and lipid disorders, underscores the complexity of genetic influences on cardiovascular risk factors, necessitating further research across diverse populations.\n\n\nConclusion\n\nThis study provides a comprehensive overview of the demographic, clinical, and genetic characteristics of AMI patients. The analysis revealed significant variations in the age and AMI distribution according to sex and weight. Female patients tended to be older than male patients, with a median age of 67 years compared to 54.5 years for males. The BMI analysis shows that the majority of the population falls within the ‘Normal’ weight category (77.84%), with smaller proportions in ‘Overweight’ (15.14%), ‘Thinness’ (4.86%), and ‘Obese’ (2.16%) categories. Hypertension (83.8%) and dyslipidemia (80.0%) were the most prevalent cardiovascular risk factors, followed by smoking (50.0%), and diabetes mellitus (33.8%). Most patients were classified as having Killip class I (93.8%), indicating mild heart failure symptoms. The clinical presentation included a higher prevalence of non-ST-elevation myocardial infarction (NSTEMI) (55.0%) than ST-elevation myocardial infarction (STEMI) (45.0%). Lipid abnormalities were common, with decreased HDL-C levels in 60.0% of patients and elevated triglycerides in 53.8% of patients. Genetic analysis of the rs1333040 polymorphism of the ANRIL gene showed that the TT genotype was the most prevalent (58.8%), but no significant associations were found between this polymorphism and biochemical parameters such as glucose, cholesterol, HDL-C, LDL-C, and triglycerides. These findings underscore the importance of understanding demographic and clinical profiles for improving AMI management and highlight the need for further research on genetic influences.\n\n\nEthical considerations\n\nEthical approval for this study was obtained from the Ethics Council in Biomedical Research at Hanoi University of Public Health on May 10, 2023, under Reference Number: 225/2023/YTCC-HD3. The study involving human participants strictly adhered to the ethical principles outlined in the Declaration of Helsinki. The protocol, meeting all ethical requirements, was approved by Hanoi University of Public Health. Approved (allowed) time: From May 10, 2023 to October 31, 2023. Data collection time: From May 15, 2023 to August 31, 2023. Written informed consent was obtained from each participant before participation in the study.",
"appendix": "Data availability statement\n\nBioStudies, Comprehensive Analysis of Demographic, Clinical, and Genetic Characteristics in Acute Myocardial Infarction Patients\n\nS-BSST1491. Retrieved from https://www.ebi.ac.uk/biostudies/studies/S-BSST1491. DOI: 10.6019/S-BSST1491 (Pham et al., 2024).\n\nThe project contains the following underlying data:\n\n• Dataset of ANRIL.csv\n\nData are available under the terms of the CC0 1.0 UNIVERSAL (CC0).\n\nBioStudies: STROBE checklist for ‘Comprehensive Analysis of Demographic, Clinical, and Genetic Characteristics in Acute Myocardial Infarction Patients’. https://www.ebi.ac.uk/biostudies/studies/S-BSST1491 (Pham et al., 2024).\n\nData are available under the terms of the CC0 1.0 UNIVERSAL (CC0)\n\nArticles reporting observational studies followed the STROBE guidelines.\n\n\nAcknowledgement\n\nWe acknowledge the cooperation and support of the outpatients and collaborators at Hoan My Cuu Long General Hospital and Kien Giang General Hospital for the time and effort devoted to this study. We also thank you for the support from Hanoi University of Public Health and Can Tho University of Medicine and Pharmacy.\n\n\nReferences\n\nByrne RA, Joner M, Kastrati A: Stent thrombosis and restenosis: what have we learned and where are we going? The Andreas Grüntzig Lecture ESC 2014. Eur. Heart J. 2015; 36(47): 3320–3331. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChapman AR, Adamson PD, Shah ASV, et al.: High-Sensitivity Cardiac Troponin and the Universal Definition of Myocardial Infarction. Circulation. 2020; 141(3): 161–171. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCongrains A, Kamide K, Oguro R, et al.: Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B. Atherosclerosis. 2012; 220(2): 449–455. PubMed Abstract | Publisher Full Text\n\nCunnington MS, Keavney B: Genetic Mechanisms Mediating Atherosclerosis Susceptibility at the Chromosome 9p21 Locus. Curr. Atheroscler. Rep. 2011; 13(3): 193–201. PubMed Abstract | Publisher Full Text\n\nDing H, Xu Y, Wang X, et al.: 9p21 is a shared susceptibility locus strongly for coronary artery disease and weakly for ischemic stroke in Chinese Han population. Circ. Cardiovasc. Genet. 2009; 2(4): 338–346. PubMed Abstract | Publisher Full Text\n\nFerreira HJ, Esteller M: Non-coding RNAs, epigenetics, and cancer: tying it all together. Cancer Metastasis Rev. 2018; 37(1): 55–73. PubMed Abstract | Publisher Full Text\n\nGao R, Patel A, Gao W, et al.: Prospective observational study of acute coronary syndromes in China: practice patterns and outcomes. J. Heart. 2008; 94(5): 554–560. Publisher Full Text\n\nGolabgir Khademi K, Foroughmand AM, Galehdari H, et al.: Association Study of rs1333040 and rs1004638 Polymorphisms in the 9p21 Locus with Coronary Artery Disease in Southwest of Iran. Iran. Biomed. J. 2016; 20(2): 122–127. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNgo HT, Nguyen TKN, Pham TNN, et al.: The combination of CYP2C19 polymorphism and inflammatory cell ratios in prognosis cardiac adverse events after acute coronary syndrome. Int. J. Cardiol. Cardiovasc. Risk Prev. 2023; 19: 200–222. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHoldt LM, Teupser D: Long Noncoding RNA ANRIL: Lnc-ing Genetic Variation at the Chromosome 9p21 Locus to Molecular Mechanisms of Atherosclerosis [Mini Review].2018; 5. Publisher Full Text\n\nHuang DL, Chen QF, Wang W, et al.: Association of rs1333040 SNPs with susceptibility, risk factors, and clinical characteristics of acute myocardial infarction patients in a Chinese Han population. Int. J. Clin. Exp. Pathol. 2018; 11(2): 727–738. PubMed Abstract\n\nLawton Jennifer S, Tamis-Holland Jacqueline E, Bangalore S, et al.: 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization. J. Am. Coll. Cardiol. 2022; 79(2): e21–e129. PubMed Abstract | Publisher Full Text\n\nLe TS, Nguyen PT, Nguyen-Ho SH, et al.: Expression of genes involved in exopolysaccharide synthesis in Lactiplantibacillus plantarum VAL6 under environmental stresses. Arch. Microbiol. 2021; 203(8): 4941–4950. PubMed Abstract | Publisher Full Text\n\nLina D, Notarangelo MF, Merlini PA, et al.: Abstract 4011: Influence Of Rs1333040, A Newly Discovered 9p21.3 Genetic Variant, On Clinical Outcomes In Early-onset Myocardial Infarction.2008; 118(suppl_18): S_818–S_818. Publisher Full Text\n\nMello BH, Oliveira GB, Ramos RF, et al.: Validation of the Killip-Kimball classification and late mortality after acute myocardial infarction. Arq. Bras. Cardiol. 2014; 103(2): 107–117. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMemon AG, Khan MQ: Echocardiographic Correlation of Clips Classification to Asses Left Ventricular Function in Patients with Acute Myocardial Infarction.2017.\n\nO’Gara PT, Kushner FG, Ascheim DD, et al.: 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Circulation. 2013; 127(4): e362–e425. PubMed Abstract | Publisher Full Text\n\nPham TNN, Tran TTL, Duong HQ, et al.: Comprehensive Analysis of Demographic, Clinical, and Genetic Characteristics in Acute Myocardial Infarction Patients. BioStudies. 2024; S-BSST1491. Reference Source\n\nQi L, Li JM, Sun H, et al.: Association between gene polymorphisms and myocardial infarction in Han Chinese of Yunnan province. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012; 29(4): 413–419. PubMed Abstract | Publisher Full Text\n\nReed GW, Rossi JE, Cannon CP: Acute myocardial infarction. Lancet. 2017; 389(10065): 197–210. Publisher Full Text\n\nRohlfs RV, Weir BS: Distributions of Hardy–Weinberg Equilibrium Test Statistics. Genetics. 2008; 180(3): 1609–1616. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStone NJ, Robinson JG, Lichtenstein AH, et al.: 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Circulation. 2014; 129(25_suppl_2): S1–S45. Publisher Full Text\n\nTemel ŞG, Ergören M: The association between the chromosome 9p21 CDKN2B-AS1 gene variants and the lipid metabolism: A pre-diagnostic biomarker for coronary artery disease. Anatol. J. Cardiol. 2019; 21(1): 31–38. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThygesen K, Alpert JS, Jaffe AS, et al.: Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018; 138(20): e618–e651. Publisher Full Text\n\nWilliams B, Mancia G, Spiering W, et al.: 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur. Heart J. 2018; 39(33): 3021–3104. Publisher Full Text\n\nWoldu B, Melku M, Shiferaw E, et al.: Phenotype, Allele and Genotype Frequency of ABO and Rhesus D Blood Groups of Blood Donors at the North Gondar District Blood Bank, Northwest Ethiopia. J. Blood Med. 2022; 13(null): 11–19. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "363879",
"date": "06 Feb 2025",
"name": "Jaroslav A Hubacek",
"expertise": [
"Reviewer Expertise genetic 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\nThe manuscript is potentially interesting, but its value would be significantly improved if the following points are implied.\nmajor comments\n1/ There is a lack of comparison with a control group - for example, is the prevalence of traditional risk factors in the general population known? 2/ Genotyping results should also be compared with at least 50 healthy individuals. There is also a lack of information on which allele is generally considered to be a risky 3/ Introduction - it would be more relevant to insert mortality and epidemiological data regarding the Vietnamese population. 4/ why are the genotyping results presented only on 80 individuals and not on the whole population of patients?\nMinor comments\n1/ Methodology - the genotyping implies that several SNPs, 32138 nucleotides apart, were analyzed, but only one is mentioned in the results. 2/ The range of ages does not match - according to the methodologies it is 40-95 years, according to the results it is 44-93 3/ it is unnecessary to repeat the numerical results, presented in tables, again in the text\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? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-937
|
https://f1000research.com/articles/11-1284/v1
|
10 Nov 22
|
{
"type": "Research Article",
"title": "Effects of scapulothoracic exercises on chest mobility, respiratory muscle strength, and pulmonary function in male COPD patients with forward shoulder posture: a randomized control trial",
"authors": [
"Kanogwun Thongchote",
"Usa Chinwaro",
"Sarawut Lapmanee",
"Kanogwun Thongchote",
"Usa Chinwaro"
],
"abstract": "Background\n\nThe postural abnormality, forward shoulder posture (FSP), is the most common cause of respiratory impairment in older individuals with chronic obstructive pulmonary disease (COPD). A recent study found that performing pectoral stretching and scapular strengthening exercises for eight weeks could reduce FSP in healthy participants. We aimed to determine the effects of pectoral stretching and scapular stabilizer strengthening exercises on FSP, chest wall mobility, respiratory muscle strength, and pulmonary function in male patients with COPD. Methods\n\nThis study was randomized clinical trial. Forty male COPD patients with FSP aged 60–90 years were included and randomly allocated to control (n=20) and exercise (n=20) groups. Following completion of the scapulothoracic exercises (three days/week, for eight weeks), respiratory functions were assessed by measuring the magnitude of FSP, chest mobility, respiratory muscle strength, and pulmonary functions. Results\n\nFSP and thoracic kyphosis angle significantly decreased compared to controls (p<0.001, p<0.001). Middle and lower chest mobility markedly increased (p<0.001, p<0.001) and the pectoralis minor index significantly improved (p<0.001). The strength of the lower trapezius and serratus anterior muscles significantly increased at week eight of the exercise training (p<0.003, p<0.001). There was a marked increase in maximum inspiratory pressure and maximum expiratory pressure (p<0.001, p<0.001). Conclusions\n\nThe eight-week combined pectoral muscles self-stretching and serratus anterior and lower trapezius strengthening exercises could be an effective treatment and/or prevention strategy for FSP reduction, leading to improved respiratory function in male COPD patients.",
"keywords": [
"COPD",
"scapulothoracic exercise",
"Respiratory muscles",
"Shoulders",
"Thoracic wall"
],
"content": "Introduction\n\nChronic obstructive pulmonary disease (COPD) is one of the most important chronic inflammatory lung diseases that leads to increased mortality and morbidity worldwide. Globally, the prevalence of COPD is expected to increase, leading to an estimated 5.4 million deaths in 2060.1 The proportion of COPD cases was higher in males (11.9%) than females (8.4%).2 In Thailand, the prevalence of COPD was 2.1% in 1999 and increased to 7.0% in 2010.3 Moreover, this disease incidence increases and outcomes deteriorate with age.4 In COPD patients, hyperinflation of the lungs induces a passive increase in chest wall rigidity and respiratory muscle weakness, and also promotes postural misalignment i.e., forward shoulder posture (FSP) or rounded shoulders.5–7\n\nFSP is characterized by the resting shoulder position being located forward from the ideal postural alignment, which is linked to scapular protraction, anterior tilt, and downward rotation, as well as being positioned anteriorly.8,9 This abnormal shoulder posture results in subacromial impingement and shoulder pain. Tightness of the pectoral muscles and weakness of the scapular muscles, especially the lower trapezius and serratus anterior, subsequently lead to a forward alignment of the shoulder posture.10,11 A reduction in pulmonary function is related to an increase in FSP.12 Therefore, poor posture resulting from FSP in COPD patients not only leads to musculoskeletal problems, but also causes deteriorating effects on the pulmonary system.\n\nMany studies have suggested that exercises can improve muscle balance, and this is considered the treatment for FSP.13–15 Stretching and strengthening exercises, especially for the serratus anterior and lower trapezius muscles, have been used to actively counteract the strength and movement loss associated with FSP.16 Therefore, diminishing the muscle imbalance in FSP is an effective treatment for musculoskeletal dysfunction and for improving pulmonary function.\n\nInterestingly, our preliminary study showed that an eight-week regimen of self-stretching the pectoral muscles and strengthening exercises for the scapular muscles can attenuate FSP, improve chest mobility, and increase respiratory muscle strength in participants without COPD. To our knowledge, this integrated exercise program was extended to COPD patients with FSP; however, the effects of these exercises have not been studied with older COPD patients. Therefore, this study aimed: (i) to investigate the effects of an exercise training program comprising pectoral self-stretching and scapular strengthening exercises on FSP, and (ii) to determine whether such an exercise rehabilitation program could also improve chest mobility, respiratory muscle strength, pulmonary function, and quality of life in geriatric patients with COPD.\n\n\nMethods\n\nA randomized controlled trial and single-blind study of all participants were performed. According to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines, stage 1–4 COPD patients were diagnosed by a respiratory medical doctor and trained spirometer personnel recruited from Nakhon Nayok Hospital and Banna Hospital in Nakhon Nayok province, Thailand. Among COPD patients, the prevalence was higher in males than in females.2 Therefore, forty male COPD patients with FSP aged 60–90 years were included, and their general appearance, personal history, and family history were characterized. A shoulder posture was forward if the distance from the anterior tip of the acromion process to the wall was longer than 2.54 cm or 1 inch.14,17 Patients with acute exacerbation, neurological, or cardiovascular problems were excluded from the study.\n\nThe sample size was calculated from a study by Gaude et al. (2014) by using the G-power program (version 3.1.9.2, RRID:SCR_013726).18 ANOVA with repeated measures was employed to determine interactions within the group (i.e., duration of intervention: baseline, week four and week eight) and interactions between groups (i.e., control vs exercise), which were used to calculate a statistical power of 0.8, α error probability of 0.05, and effect size of 0.38. The sample size from the calculation was 16 participants per group. However, assuming that 20% would drop out equally, four additional participants were added per group. Therefore, two groups with 20 participants in each were conducted in the present study.\n\nA flowchart of the process used in this study is provided in Figure Supplementary 1. Initially, 52 COPD (stage 1–4) patients were assessed for eligibility. Twelve volunteers were excluded from the study as they either declined to participate (n=1) or did not meet the inclusion criteria (n=11). The remaining 40 participants were randomly allocated into two groups: a control and an exercise group, with 20 participants in each. Two participants in the control group were excluded during the eight weeks as they exacerbated their COPD condition. In the exercise group, four participants were excluded in the fourth week due to COPD exacerbation (n=1) or discontinuation of their exercise intervention (n=3). However, the analysis of intention to treat with the last observation carried forward (LOCF) method was still conducted for them in this study. Theoretically, LOCF replaces missing outcomes with the last observed outcome. The intra-rater reliability of the tester was examined for all parameters. Each testing procedure was performed by the same investigator. The intra-class correlation coefficient (ICC3,1) was shown to lie between 0.960–0.997, which is considered a demonstration of an excellent level of reliability (p<0.01).\n\nAssessment of the primary outcomes included measurement of the magnitude of FSP, the amplitude of chest mobility, respiratory muscle strength, and pulmonary functions. These parameters are the gold standard measurements and tools for assessment of respiratory muscle strength, and pulmonary functions according to American Thoracic Society (ATS) recommendation. In addition, the assessment of the secondary outcomes included measurement of these items: pectoralis minor length, degree of thoracic kyphosis, serratus anterior and lower trapezius muscle strength, symptoms and quality of life, respectively. Baseline measurements were performed at the start of the study and were tested after four weeks and after eight weeks of the training program.\n\nForward shoulder posture\n\nThe magnitude of FSP was assessed using the vernier height gauge (Mitutoyo 506-207, Japan) in the sitting position. Measurement of the distance from the wall to the anterior aspect of the participant’s acromion process indicated the magnitude of FSP in centimeters.19\n\nChest wall mobility\n\nThe amplitude of chest mobility was shown through the amplitude of the circumference of the thoracic wall during full expiration and inspiration. Three levels of chest wall circumference, upper, middle, and lower chest, were determined with apparent landmarks on the subjects’ skin.20 A measuring tape was used to measure the level of chest expansion in centimeters.\n\nStrength of respiratory muscles\n\nInspiratory and expiratory muscle strength was determined by the measurement of maximum voluntary inspiratory and expiratory pressures (MIP and MEP) in centimeters of water pressure (cmH2O) using a respiratory pressure meter (Micro RPM, Micro Medical Ltd., Rochester, UK). The evaluation followed the protocol of the American Thoracic Society/European Respiratory Society (ATS/ESR).8,21 The measurement was performed for three to five maximal maneuvers within the range of 5–10% reproducibility and acceptability.22\n\nPulmonary functions\n\nAccording to the ATS/ESR guideline, spirometry was performed for a pulmonary function test in the sitting position. Volunteers were instructed to deeply inhale and forcefully exhale through a spirometer (Viasys Micro Lab 3500, UK) for a minimum of three maneuvers, but only eight repetitions. The acceptable repeatability of each maneuver followed the criteria of the ATS/ESR guideline.23 The maximum values of forced vital capacity (FVC), forced expiratory volume within 1 sec (FEV1), and FEV1/FVC were recorded in percent predicted.\n\nPectoralis minor length\n\nLeft and right pectoralis minor lengths were measured using the vernier caliper (530-101 series, Mitutoyo, Japan) and the pectoralis minor index (PMI) was calculated. In a relaxed sitting position, markings were made on the inferior angle of the coracoid process and the fourth costosternal junction. On each side, the distance between these markers was measured in millimeters.24\n\nDegree of thoracic kyphosis\n\nPostural thoracic kyphosis was evaluated using a flexible ruler. In the standing position, the spinous process of the seventh cervical vertebra and the twelfth thoracic vertebra were marked on the volunteer’s skin. At that point, the flexible ruler curved along the thoracic spines, and the thoracic angle was computed using the flexicurve method.9\n\nStrength of scapulothoracic muscles\n\nSerratus anterior and lower trapezius muscle strength tests were performed, as described by previous studies.5,13 The resistance force from the maximum isometric contraction was measured by the hand-held dynamometer (Baseline electronic push/pull dynamometer, Model 12-0342, Ufam Decoration Co., LTD) and was normalized by the body weight (in kilograms).\n\nSymptom of breathlessness\n\nThe breathlessness score was assessed using a rate from the modified British Medical Research Council (mMRC). This method evaluates the characteristics the breathlessness which are related to health status and mortality risk.25 An mMRC score<2 is identified as small breathlessness and an mMRC score≥2 is a large breathlessness.\n\nQuality of life\n\nQuality of life was assessed using the COPD assessment test (CAT). All participants were evaluated by CAT for quality of life. It is well accepted to have a good correlation with COPD health status measured by St. George's Respiratory Questionnaire (SGRQ). The validity of the Thai CAT questionnaire was moderately correlated (r=0.652) with the quality of life questionnaire (SGRQ). The Thai CAT questionnaire has acceptable reliability and validity. It can be expected to serve as a short and simple tool for assessing the health status of Thai COPD patients.26 The CAT has eight items including dyspnea, cough, sputum production, wheeze, systemic symptoms of fatigue, sleep disturbance, limitation in daily activities, social life, emotional health, and feeling control. CAT scores range from 0–40. A CAT score<10 is identified as having a low impact on health status, 11–20 is identified as a moderate impact on health status, 21–30 is identified as a high impact on health status, and >30 is identified as a very high impact to health status.27\n\nEach participant received routine conventional medical treatment with the same physical therapy, including breathing control with the pursed-lip technique for both groups. For the control group, the participants received conventional treatment without conducting the exercise training program to reduce FSP throughout the eight weeks of the study. For the exercise group, the participants’ vital signs were measured before exercise and then during exercise, as shown in Figure Supplementary 2. The exercise protocol in this study was supervised and applied to all participants by the same investigator. The participants followed an exercise training program for reducing FSP that was modified from previous studies.28–30 The exercise plan comprised pectoral muscles self-stretching at 90° and 120° of shoulder abduction with external rotation and serratus anterior and lower trapezius strengthening exercises. The exercises were done three days a week for eight weeks.\n\nFor the stretching exercise, the participants were positioned in a standing position behind a line. The participants actively stretched their pectoral muscles by moving their trunks in rotation to the opposite side, one at a time, for each side. This was done with five repetitions/set, one set/day, 60 seconds for holding, and a 30-second break between each stretch.31\n\nFor the lower trapezius strengthening, a scapular posterior tilting exercise was performed in a prone sitting position, as followed in the previous studies.28,30,32 Push-ups on stable table support were modified from a study by Kisner and Colby in 2013 for strengthening the serratus anterior.28\n\nIntention-to-treat analysis with the LOCF method was performed in this study. The results were expressed as mean±SE and were analyzed by the IBM SPSS program version 25 (SCR_002865). An unpaired t-test was used to test the characteristics of the participants at baseline. A two-way ANOVA was used for comparison of the main effects of all parameters between baseline, week four, and week eight of the exercise training. The level of significance of the statistical tests was set at p<0.05.\n\n\nResults\n\nThe demographic data of COPD participants in the control and exercise group are shown in Table 1. There was no significant difference in any of the characteristics of the subjects, which were age, body mass index (BMI), weight, height, number of participants in each stage of COPD, CAT for quality of life, and mMRC for breathlessness score (p>0.05). The baseline characteristics of all participants in the control and exercise groups are shown in Table 1. There were no significant differences in the baseline data between the control and the exercise groups, which reflects the success of the randomization in creating the intervention and control groups with similar baseline characteristics. The interaction between time and intervention was significantly shown in the magnitude of FSP, MIP, and MEP (p<0.05).\n\n\n\n- Low impact (< 10 point)\n\n\n\n- Moderate impact (10–20 points)\n\n\n\n- High impact (21–30 points)\n\n\n\n- Very high impact (> 30 points)\n\n\n\n- Low impact (<2 points)\n\n\n\n- High impact (≥2 points)\n\n\n\n- Upper part (cm)\n\n\n\n- Middle part (cm)\n\n\n\n- Lower part (cm)\n\n\n\n- MIP (cmH2O)\n\n\n\n- MEP (cmH2O)\n\n\n\n- FVC (%predicted)\n\n\n\n- FEV1 (%predicted)\n\n\n\n- FEV1/FVC (%predicted)\n\na Fisher’s exact test.\n\nEffects of eight-week scapulothoracic exercises on FSP, PMI, lower trapezius and serratus anterior muscle strength, and thoracic kyphosis\n\nThe key results of the side measurements of the structural changes for FSP, PMI, thoracic kyphosis, and strength of lower trapezius and serratus anterior muscles are shown in Figures 1 and 2. Regarding the changes in FSP within each group (Figure 1A), the control group showed a significantly increased FSP at week eight when compared to baseline, whereas the exercise group had a reduction in FSP at both weeks four and eight when compared to baseline (p<0.001, p<0.001, respectively) and compared to the control (p<0.01, p<0.001, respectively). These results show that FSP gradually increased with time in COPD patients without exercise, whereas performing the eight-week exercise training could ease FSP in COPD patients from week four to week eight of performing the exercise training.\n\n†††p<0.001 compared to baseline, *p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control. cm=centimeters.\n\n††p<0.01 compared to baseline, †††p<0.001 compared to baseline, ##p<0.01 compared between four weeks and eight weeks, *p<0.05 compared to control, **p<0.01 compared to control. N/kgbw=newtons per kilogram of body weight.\n\nAs shown in Figure 1B, there were no changes in PMI within the control group. However, the exercise group showed significantly improved PMI when compared to their baseline at week four (p<0.001) and week eight (p<0.001) of the training. There was also an incremental increase of PMI at week eight (p=0.008) when compared to the control.\n\nRegarding thoracic kyphosis (Figure 1C), the exercise group displayed a significantly reduced degree of thoracic kyphosis at week four (p<0.001) and week eight (p<0.001) when compared to baseline. These results demonstrate that the exercise program improved the alignment of the thoracic spine by improvement of the degree of thoracic kyphosis from week four to week eight of the exercise training.\n\nThe two major scapular stabilizer muscles, namely the lower trapezius and serratus anterior, were evaluated (Figure 2A and B). When compared to the baseline, the exercise group demonstrated a significantly increased amount of force generated by the lower trapezius and serratus anterior muscles at week four (p<0.001; p<0.001) and at week eight (p=0.003; p<0.001), whereas the force was not changed in the control group. Additionally, there was a marked increase in lower trapezius and serratus anterior muscle force observed at week eight of the training when compared with the control group (p=0.01; p=0.09).\n\nThese results show that reducing FSP by performing eight weeks of self-stretching the pectoral muscles and scapular muscle strengthening exercises, including the lower trapezius and serratus anterior, can improve the pectoralis minor muscle length. This is represented by PMI and the scapular muscle strength, especially in the lower trapezius and serratus anterior muscles.\n\nThe three parts of the chest wall, including the upper, middle, and lower parts, were evaluated regarding chest mobility or expansion (Figure 3A–C). Compared to baseline, the exercise group showed significantly increased middle (p<0.001) and lower (p<0.001) chest expansion at week four and week eight of the training course. When compared to the control (p=0.039), the exercise group showed an incremental increase in middle chest expansion in weeks four and eight, whereas the lower chest showed improvement only at week eight. However, the upper chest expansion did not show any statistically significant change during the four to eight weeks of training exercises.\n\n†p<0.05 compared to baseline, ††p<0.01 compared to baseline, †††p<0.001 compared to baseline, *p<0.05 compared to control, **p<0.01 compared to control. cm=centimeters.\n\nThe strength of the inspiratory and expiratory muscles was measured as the maximal inspiratory (MIP) and expiratory pressure (MEP), respectively (see Figure 4A and B). Compared to baseline, the exercise group showed a significantly increase in MIP and MEP at week four (p<0.001 and p<0.001, respectively) and week eight (p<0.001 and p<0.001, respectively). When compared to the control, the MIP and MEP of the exercise group were significantly increased at week eight (p<0.001 and p<0.001, respectively) through the training exercises.\n\n†††p<0.001 compared to baseline; *p<0.05 compared to control; ***p<0.001 compared to control. cmH2O=centimeters of water.\n\nRegarding the pulmonary function test, the exercise group did not display a significant difference in the pulmonary function parameters: the %FVC predicted, %FEV1 predicted, and %FEV1/FVC when compared with baseline and with the control group, as shown in Table Supplementary 1.\n\nConsidering the mMRC and CAT score, breathlessness (mMRC) and quality of life of the participants with COPD (CAT) were not changed in the exercise group when compared within the group and with the control, as illustrated in Table Supplementary 2. These results imply that an eight-week exercise training program could not change the patients’ quality of life. However, the training program did not induce the severity of breathlessness in the older participants with COPD.\n\n\nDiscussion\n\nThis study evaluated the effects of an eight-week exercise regimen for reducing FSP on chest expansion, respiratory muscle strength, and pulmonary function in COPD patients. The results showed that performing an exercise training program that included stretching pectoral muscles and strengthening scapular muscles three days a week for eight weeks improved chest expansion and respiratory muscle strength.\n\nIn the exercise group, there was a significant reduction in the degree of FSP with an increase in PMI. Similarly, soft tissue mobilization and stretching of the pectoralis muscles could reduce FSP, which led to alleviation of scapular anterior tilting in the sagittal plane and scapular internal rotation in the transverse plane.20 In addition, the viscoelastic effect of muscle stretching increases the range of motion, which is related to a reduction in the resistance to stretch and muscle stiffness, and an increase in muscle compliance.11 Reducing tension in the stretched pectoral muscles allows them to lengthen and also decreases FSP.\n\nTo correct muscle imbalance, the strengthening exercises for the agonist's muscles are important to counteract muscle weakness related to FSP. The lower trapezius and serratus anterior are the primary agonist muscles to control posterior tilting and upward rotation of the scapular, which are necessary for the subacromial space expansion in FSP.33 Therefore, activation of the lower trapezius and serratus anterior muscles is important for correcting muscle imbalance and re-establishing the normal plane of the scapula in COPD patients with FSP.\n\nOur results showed a significant increase in the magnitude of lower trapezius and serratus anterior muscle force in the exercise group. Therefore, eight-week scapular strengthening exercises focusing on the lower trapezius and serratus anterior muscles after stretching the pectoral muscles could be applied as a potential method to increase the length of the pectoralis minor muscle and the strength of the scapular muscles. An increase in scapular stabilizing muscle strength could adjust the proprioception of shoulder joint and restore the scapular position to the normal scapula-humeral alignment, thus reducing FSP in COPD patients.34 These findings are consistent with the eight-week exercise program, which is comprised of stretching the anterior shoulder muscles (i.e., pectoralis, levator scapulae, and sternocleidomastoid) and strengthening of the posterior shoulder muscles (i.e., middle trapezius, lower trapezius, and serratus anterior) that could decrease FSP in swimmers.35\n\nThis study showed that the correction of the upper quadrant muscles in COPD patients improved, not only shoulder posture, but also the posture of the thoracic spine. These results are consistent with the findings of Kim et al.(2018) who reported that rehabilitation with resistive and stretching exercises could re-balance muscle force and restore muscle elasticity, thus reducing FSP and thoracic kyphosis angle.36\n\nSome recognize that poor posture with FSP limits respiratory function. Alteration of upper body alignment changes respiratory muscle length, especially the diaphragm and intercostal muscles, affecting its force-generating capacity.37 The tightness of the pectoralis muscle resulting from FSP limits the mobility and compliance ability of the chest wall to create maximal lung capacity during inspiration.23 COPD patients with FSP have a reduced ability to raise and expand the thorax, which limits their lung capacity.32 Regarding FSP reduction, pectoralis muscle stretching causes the pectoralis muscle fibers to lengthen, as shown by the increased PMI, and the compliance of the anterior chest wall is improved.\n\nOur findings showed an improvement in chest wall mobility when compared with the control. The increment in chest mobility was shown in the middle section, which is the area of the pectoralis minor muscle. Reduction of FSP provides the approximation of the ribs to the pelvis, decreases intra-abdominal pressure, and allows the diaphragm to descend caudally.14 Presumably, the diaphragm can work more effectively to expand the lower chest and create maximum contraction force during respiration, as indicated in the increased lower chest mobility and respiratory muscle strength found in this study.\n\nConsidering the pulmonary function, the exercises for reducing FSP led to no significant improvement of the pulmonary functions, including FEV1, FVC, and FEV1/FVC. This indicates that correcting FSP does not alleviate the respiratory abnormalities in COPD patients. Our findings are consistent with a study by Wang (2015), in which no noticeable changes were found in the respiratory functions (i.e., FEV1, FVC, and FEV1/FVC) of COPD patients after posture was improved by stretching and mobilization of the thoracic cage.38 The explanation for the non-improvement of the pulmonary function in the COPD participants was reported as being due to the advanced age, advanced thoracic kyphosis, and the longer duration of disease in the participants. In addition, smoking history is associated with the severity of airway inflammation in COPD patients. These factors result in structural deterioration, making it difficult to restore.\n\nThe prevention of aggravated symptoms was also found in this study as it was illustrated that there were no changes in the breathlessness score and quality of life in the exercise-trained COPD participants when compared to their control. Our findings are consistent with a study by McKeough (2016), in which no significant decrease in dyspnea in a patient with stable COPD was reported after upper training.39 However, in a meta-analysis study, upper limb training was given in a shorter period of three to eight weeks and there was a significant decrease in dyspnea, suggesting that a short duration of upper limb training can reduce dyspnea in stable COPD patients.40 Quality of life was assessed by CAT score and there were no changes in the exercise-trained COPD participants when compared to their control. Consequently, this study only shows that upper limb training improves or corrects shoulder posture in stable COPD but does not improve the quality of life in a patient with COPD.39\n\nThe limitations of this study included the reduction in FSP found in this study resulting from the combination of a static self-stretching and strengthening exercise program. Firstly, differential analysis between pectoral stretching and scapular muscle strengthening exercises should be performed in future studies. Secondly, the findings of this study cannot be generalised to other situations or conditions, such as female patients or males with other pulmonary diseases, as the present study was only comprised of 60 to 90-year-old male COPD patients. Thirdly, the detraining effects after the eight-week exercise program could be observed in order to observe respiratory muscular adaptations. Finally, only a single-blind study was performed in the present research because of the limited number of investigators. To minimize bias, the blinding of all therapists and assessors should be considered in any future research.\n\n\nConclusions\n\nBased on these findings, the eight-week regimen of pectoral stretching and scapular strengthening exercises could improve pectoral muscle tightness and scapular muscle strength i.e., lower trapezius and serratus anterior muscles, which can lead to significantly reduced FSP in male COPD patients. There was increased chest mobility and respiratory muscle strength following this exercise intervention. Thus, the results might provide perspectives for the improvement of the quality of life in male COPD patients.\n\n\nEthical approval\n\nThis study was approved by the Institutional Review Board of the Nakhon Nayok Hospital (REC 10/2560) and the Nakhon Nayok Public Health Office (NPHO 2018-004) by the World Medical Association’s Declaration of Helsinki.\n\n\nInformed consent\n\nData collection and the need for informed consent were approved by the Thai Clinical Trial Registry (registration number TCTR20180525001). Written informed consent was obtained from each of the participants.\n\n\nAuthor contributions\n\nConceptualization, KT, SL; Data curation, KT, UC, SL; Formal Analysis, KT; Funding acquisition, KT, SL; Investigation, KT, UC, SL; Methodology, KT, UT; Visualization, KT, SL; Project administration, KT; Supervision, SL; Writing–original draft, KT, SL; Writing–review & editing, UC, SL, KT.\n\n\nSubmission statement\n\nAll authors have read and agree with manuscript content. The manuscript has not been published and is not under consideration for publication elsewhere.\n\n\nAcknowledge Statement\n\nThe authors thank all the participants for their participation. We sincerely thank Ms. Apinyaluck Da-asa from the Nakhon Nayok Hospital, and Mrs. Hathaichanok Prateepchinda from the Ban Na Hospital for the management of patients in this study.",
"appendix": "Data availability\n\nFigshare: [Additional methods], https://doi.org/10.6084/m9.figshare.21312333.\n\nThe project contains the following underlying data:\n\n- Methods\n\nData repository name: [Supplementary data]. https://doi.org/10.6084/m9.figshare.21312378.\n\nThis project contains the following extended data:\n\n- Supplementary Table 1. Group comparison of pulmonary functions at baseline (week zero), week four, and week eight of the study period.\n\n- Supplementary Table 2. COPD assessment test (CAT) and modified Medical Research Council (mMRC) dyspnea scale; comparison at baseline, and at four and eight weeks of the study period.\n\n- Supplementary Figure 1. Flow diagram for the study.\n\n- Supplementary Figure 2. Exercise intervention comprised of pectoral stretching and scapular stabilizer exercise. Pectoralis major (clavicular part) and pectoralis minor stretching exercise: (A and B) starting position, (C and D) stretch at the end range of motion. Scapular stabilizer exercises: (E) serratus anterior exercise push-up on table, scapular posterior tilt (SPT) exercise: (F) starting position (G) SPT in long arm. (H) Progression of strengthening exercise protocol was modified from ACSM’s prescription.\n\n- Questionnaire: appendix form.\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\nVogelmeier CF, Criner GJ, Martinez FJ, et al.: Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary. Eur. Respir. J. 2017; 49(3): 1700214. PubMed Abstract | Publisher Full Text\n\nJoo J, Himes B: Gene-Based Analysis Reveals Sex-Specific Genetic Risk Factors of COPD. AMIA Annu. Symp. Proc. 2021. 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PubMed Abstract | Publisher Full Text\n\nMcCarthy B, Casey D, Devane D, et al.: Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2015; 2. Publisher Full Text\n\nGaude G, Savadatti R, Hattiholi J: Postural correction for kyphosis improves the dyspnea index and pulmonary functions in patients with chronic obstructive pulmonary disease: A randomized trial over 12 weeks. Int. J. Res. Health Allied Sci. 2014; 3(1): 44. Publisher Full Text\n\nTate AR, McClure PW, Kareha S, et al.: Effect of the scapula reposition test on shoulder impingement symptoms and elevation strength in overhead athletes. J. Orthop. Sports Phys. Ther. 2008; 38(1): 4–11. PubMed Abstract | Publisher Full Text\n\nWong CK, Coleman D, diPersia V, et al.: The effects of manual treatment on rounded-shoulder posture, and associated muscle strength. J. Bodyw. Mov. Ther. 2010; 14(4): 326–333. PubMed Abstract | Publisher Full Text\n\nCelli BR, MacNee W; ATS/ERS Task Force: Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur. Respir. J. 2004; 23(6): 932–946. PubMed Abstract | Publisher Full Text\n\nOzsoy I, Kahraman BO, Ozsoy G, et al.: Effects of an integrated exercise program including “functional” inspiratory muscle training in geriatric individuals with and without chronic obstructive pulmonary disease. Ann. Geriatr. Med. Res. 2021; 25(1): 45–54. PubMed Abstract | Publisher Full Text\n\nPutt MT, Watson M, Seale H, et al.: Muscle stretching technique increases vital capacity and range of motion in patients with chronic obstructive pulmonary disease. Arch. Phys. Med. Rehabil. 2008; 89(6). Publisher Full Text\n\nStruyf F, Meeus M, Fransen E, et al.: Interrater and intrarater reliability of the pectoralis minor muscle length measurement in subjects with and without shoulder impingement symptoms. Man. Ther. 2014; 19(4): 294–298. PubMed Abstract | Publisher Full Text\n\nMunari AB, Gulart AA, Dos Santos K, et al.: Modified medical research council dyspnea scale in GOLD classification better reflects physical activities of daily living. Respir. Care. 2018; 63(1): 77–85. PubMed Abstract | Publisher Full Text\n\nPothirat C, Kiatboonsri S, Chuchottaworn C: Validation of the new COPD assessment test translated into Thai in patients with chronic obstructive pulmonary disease. BMC Pulm. Med. 2014; 14. PubMed Abstract | Publisher Full Text\n\nJones PW, Tabberer M, Chen WH: Creating scenarios of the impact of COPD and their relationship to COPD assessment test (CAT™) scores. BMC Pulm. Med. 2011; 11. PubMed Abstract | Publisher Full Text\n\nKisner C, Colby LA: Therapeutic Exercise Foundations and Techniques. 6th ed.Philadelphia, FA:Davis Company;2013.\n\nPark HC, Kim YS, Seok SH, et al.: The effect of complex training on the children with all of the deformities including forward head, rounded shoulder posture, and lumbar lordosis. J. Exerc. Rehabil. 2014; 10(3): 172–175. PubMed Abstract | Publisher Full Text\n\nLee JH, Cynn HS, Yoon TL, et al.: The effect of scapular posterior tilt exercise, pectoralis minor stretching, and shoulder brace on scapular alignment and muscles activity in subjects with round-shoulder posture. J. Electromyogr. Kinesiol. 2015; 25(1): 107–114. PubMed Abstract | Publisher Full Text\n\nSangtarash F, Manshadi FD, Sadeghi A: The relationship of thoracic kyphosis to gait performance and quality of life in women with osteoporosis. Osteoporos. Int. 2015; 26(8): 2203–2208. PubMed Abstract | Publisher Full Text\n\nKluemper M, Uhl T, Hazelrigg H: Effect of stretching and strengthening shoulder muscles on forward shoulder posture in competitive swimmers. Sport Rehabil. 2006; 15(1). Publisher Full Text\n\nTsuruike M, Ellenbecker TS: Serratus anterior and lower trapezius muscle activities during multi-joint isotonic scapular exercises and isometric contractions. J. Athl. Train. 2015; 50(2): 199–210. PubMed Abstract | Publisher Full Text\n\nRavichandran H, Janakiraman B, Gelaw AY, et al.: Effect of scapular stabilization exercise program in patients with subacromial impingement syndrome: a systematic review. J. Exerc. Rehabil. 2020; 16(3): 216–226. PubMed Abstract | Publisher Full Text\n\nLynch SS, Thigpen CA, Mihalik JP, et al.: The effects of an exercise intervention on forward head and rounded shoulder postures in elite swimmers. Br. J. Sports Med. 2010; 44(5): 376–381. PubMed Abstract | Publisher Full Text\n\nKim MK, Lee JC, Yoo KT: The effects of shoulder stabilization exercises and pectoralis minor stretching on balance and maximal shoulder muscle strength of healthy young adults with round shoulder posture. J. Phys. Ther. Sci. 2018; 30(3): 373–380. PubMed Abstract | Publisher Full Text\n\nGonçalves MA, Lisboa LG, Tavares MGS, et al.: Comparison of diaphragmatic mobility between COPD patients with and without thoracic hyperkyphosis: a cross-sectional study. J. Bras. Pneumol. 2018; 44(1): 5–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang JS: Effect of joint mobilization and stretching on respiratory function and spinal movement in very severe COPD with thoracic kyphosis. J. Phys. Ther. Sci. 2015; 27(10): 3329–3331. PubMed Abstract | Publisher Full Text\n\nMcKeough ZJ, Velloso M, Lima VP, et al.: Upper limb exercise training for COPD. Cochrane Database Syst. Rev. 2016; 2016(11): CD011434. PubMed Abstract | Publisher Full Text\n\nTarigan AP, Ananda FR, Pandia P, et al.: The Impact of upper limb training with breathing maneuver in lung function, functional capacity, dyspnea scale, and quality of life in patient with stable chronic obstructive of lung disease. Open Access Maced. J. Med. Sci. 2019; 7(4): 567–572. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "166096",
"date": "27 Mar 2023",
"name": "Pattanasin Areeudomwong",
"expertise": [
"Reviewer Expertise Exercise therapy",
"Manual therapy",
"Musculoskeletal Physiotherapy"
],
"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 looked at the effects of scapulothoracic muscle stretching and strengthening exercises on COPD outcome outcomes. Although the major sources of chest wall problems, such as barrel chest shape, which commonly occurs in COPD patients, are not addressed directly in this work, it is interesting to apply simple interventions to address the consequences of COPD in terms of scapulothoracic muscle imbalance. My suggestions for improving this manuscript are as follows:\nTitle:\n\"A randomized control trial\" should be \"a randomized controlled trial\" in title of the study. Please double-check the manuscript for spelling, typos, and grammatical errors.\nAbstract:\nWhen compared to the control group, it is unclear which intervention improves outcome measures. Please explain such intervention in the results section.\nIntroduction:\nIn COPD patients, lung hyperinflation reduces chest wall mobility and causes poor posture, such as rounded shoulders and scapulothoracic muscle imbalance. Because the main problems of chest wall rigidity, respiratory muscle weakness, and lung hyperinflation are not solved by the interventions in this study, pectoral muscle stretching and lower trapezius and serratus anterior muscle strengthening exercises may temporarily improve such COPD problems. As a result, as I mentioned in the introduction section, the authors should provide possible mechanisms of used interventions for improving outcomes.\n\nPlease explain the study's gap and why it is important to examine current interventions in older COPD patients at various stages of COPD.\nMethods\nFor the study, researchers enrolled COPD patients in stages 1-4. Do the various stages of COPD affect patients' exercise performance and tiredness?\n\nAre COPD patients with musculoskeletal problems, such as pain and shoulder joint stiffness, excluded from the study?\n\nWhat parameter is used to estimate an effect size of 0.38?\n\nHow many times does the assessor measure each outcome?\n\nPlease double-check whether the paper cited at number 9 in the list proposes a method of measuring thoracic kyphosis.\n\nOn Page 5, I do not believe that breathing control with pursed lips is merely a routine conventional medical and physiotherapy treatment for COPD.\n\nPlease rewrite pectoral muscle stretching. Is each arm fixed for the purpose of stretching?\n\nWhy don't the researchers use two-way repeated measures ANOVA instead of two-way ANOVA for the three outcome measurement periods?\nResults:\nPage 7: What are \"the key results of the side measurements...\"?\n\nBecause the figures show both within- and between-group findings, \"within-group comparison\" should be indicated in all figure captions.\nDiscussion:\nPlease provide additional reasons why improvements in rounded shoulders, respiratory muscle strength, and scapulothoracic muscle flexibility and strength in COPD patients do not correlate with unchangeable lung function, dyspnea, and quality of life.\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?\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": "12151",
"date": "20 Aug 2024",
"name": "Sarawut Lapmanee",
"role": "Author Response",
"response": "Title: - \"A randomized control trial\" should be \"a randomized controlled trial\" in title of the study. Please double-check the manuscript for spelling, typos, and grammatical errors. Thank you for your suggestion. We have already used \"a randomized controlled trial\" in the title of the study. Additionally, we have double-checked the manuscript for spelling, typos, and grammatical errors. Abstract: - When compared to the control group, it is unclear which intervention improves outcome measures. Please explain such intervention in the results section. We have made the correction as per your suggestion by adding \"In the COPD group with combined pectoral muscles self-stretching and scapular strengthening exercise\" at the beginning of the results section of the abstract. Introduction: - In COPD patients, lung hyperinflation reduces chest wall mobility and causes poor posture, such as rounded shoulders and scapulothoracic muscle imbalance. Because the main problems of chest wall rigidity, respiratory muscle weakness, and lung hyperinflation are not solved by the interventions in this study, pectoral muscle stretching and lower trapezius and serratus anterior muscle strengthening exercises may temporarily improve such COPD problems. As a result, as I mentioned in the introduction section, the authors should provide possible mechanisms of used interventions for improving outcomes. Improvements in rounded shoulders, respiratory muscle strength, and scapulothoracic muscle flexibility and strength in COPD patients are important for managing the disease but do not necessarily correlate with changes in lung hyperinflation, lung function, dyspnea (shortness of breath), and quality of life. Several reasons and possible mechanisms of used interventions for improving outcomes due to nature of COPD. 1. Irreversible Lung: Damage COPD involves chronic and irreversible damage to the lung tissues and airways. While muscle exercises can improve the mechanics of breathing, they cannot reverse the structural damage or inflammation within the lungs. 2. Fixed Airway Obstruction: The primary issue in COPD is the persistent airflow limitation caused by airway narrowing and destruction of alveoli. This limitation cannot be significantly altered by improving muscle strength and flexibility. 3. Hyperinflation: During physical exertion, COPD patients often experience dynamic hyperinflation, where trapped air in the lungs increases, further reducing the efficiency of breathing. This condition is not directly affected by improvements in muscle strength or posture. 4. Secondary Gains: While improvements in muscle strength and chest wall mobility do not directly change barrel chest shape, lung hyperinflation, they can lead to better management of symptoms, enhanced exercise tolerance, and potentially slower progression of disability. These benefits, while significant, may not be immediately reflected in traditional measures of lung function or quality of life scales. In summary, while scapulothoracic muscle balance exercises offer significant benefits in terms of posture, muscle strength, and flexibility, they do not directly address the primary pathological changes in COPD that drive lung hyperinflation, lung function decline, dyspnea, and overall quality of life. However, they play a crucial role in the comprehensive management of the disease, contributing to better symptom management and functional ability. - Please explain the study's gap and why it is important to examine current interventions in older COPD patients at various stages of COPD. The primary gap identified in the study is the lack of research focusing on the effects of pectoral stretching and scapular stabilizer strengthening exercises on forward shoulder posture (FSP) and associated respiratory impairments specifically in older patients with chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated the benefits of these exercises in healthy individuals, but there is limited evidence regarding their impact on COPD patients, particularly across different severities of the disease. Importance of examining interventions across all severity of COPD 1. Variable impact of COPD: COPD affects individuals differently depending on the severity of the disease. Patients with mild COPD might have different rehabilitation needs compared to those with severe COPD. Understanding how these exercises benefit patients across the entire spectrum of disease severity is crucial for developing tailored treatment plans. 2. Personalized rehabilitation programs: By examining the effects of these exercises in patients with varying COPD severities, clinicians can better personalize rehabilitation programs. This ensures that each patient receives the most appropriate and effective interventions for their specific condition. 3. Comprehensive care: COPD is a progressive disease, and interventions effective at one stage might not be as effective at another. Investigating the benefits of pectoral stretching and scapular strengthening exercises across all severity levels can provide insights into the most effective timing and intensity of these interventions. 4. Maximizing clinical outcomes: Effective management of COPD requires strategies that can address the wide range of symptoms and complications associated with the disease. By understanding how these exercises impact respiratory function, chest mobility, and muscle strength at different stages, healthcare providers can maximize clinical outcomes. 5. Informed decision-making: Robust evidence on the efficacy of these exercises across all severities of COPD will aid clinicians in making informed decisions about incorporating these exercises into routine care. This can lead to more consistent and evidence-based practices in the management of COPD. 6. Preventative and therapeutic benefits: Identifying the benefits of these exercises in both early and advanced stages of COPD can help in formulating preventative strategies as well as therapeutic interventions. Early intervention might slow disease progression, while continued exercise in later stages can help maintain function and reduce complications. Therefore, addressing the study gap by investigating the effects of pectoral stretching and scapular strengthening exercises in older COPD patients across all severities of the disease is crucial. It will help develop comprehensive, evidence-based rehabilitation strategies that improve respiratory function, reduce FSP for COPD patients at every stage of their condition. Methods: - For the study, researchers enrolled COPD patients in stages 1-4. Do the various stages of COPD affect patients' exercise performance and tiredness? No, the various stages of COPD did not affect patients' exercise performance and tiredness in this study because we adjusted the exercise protocol, modified from ACSM 2014, for each patient based on their tolerance. We also controlled the Rating of Perceived Exertion (RPE) to not exceed 4/10. - Are COPD patients with musculoskeletal problems, such as pain and shoulder joint stiffness, excluded from the study? No, COPD patients with musculoskeletal problems were not excluded from this study, even though musculoskeletal pain and shoulder joint stiffness were listed in the exclusion criteria. - What parameter is used to estimate an effect size of 0.38? We used an effect size of 0.38 derived from a randomized trial over 12 weeks by Ghanbari A et al. (2008) from maximal inspiratory pressure (PImax) as a parameter for sample size calculations. - How many times does the assessor measure each outcome? Assessment of the outcomes was performed three times. Baseline measurements were performed at the start of the study and were tested after four weeks and after eight weeks of the training program. - Please double-check whether the paper cited at number 9 in the list proposes a method of measuring thoracic kyphosis. Thank you for your feedback. We would like to clarify that reference number 9 ((Borstad and Ludewig, 2005) correctly addresses the position of FSP and is not cited for measuring thoracic kyphosis. - On Page 5, I do not believe that breathing control with pursed lips is merely a routine conventional medical and physiotherapy treatment for COPD. Conventional physical therapy treatment for the control group consisted of pursed-lip breathing exercises, education on relaxation techniques, and training in coughing and huffing. - Please rewrite pectoral muscle stretching. Is each arm fixed for the purpose of stretching? Pectoral muscles self-stretching exercise 1.1 Stretching pectoralis major muscle (clavicular part) and pectoralis minor muscle - The participants were positioned in a standing position behind white line, with 90º shoulder abduction and 90º elbow flexion at corner as shown in Figure 1 (A) - The participants actively stretch pectoral muscle by moving trunk rotation to the opposite side as shown in Figure 1 (B) - Sustain a stretching for 60 seconds the end range of motion without pain. Fully breathe in and out with pursed lip. Then, return to starting position. - Stretching exercise will be performed 5 times/set, 1 set/day, 3 days/week, for 8 weeks 1.2 Stretching pectoralis major muscle (sternal costal part) - The participant will be positioned in a standing position behind yellow line, with 120º shoulder abduction and elbow flexion at the corner as shown in Figure 2 (A) - The participants actively stretch pectoral muscle by moving trunk rotation to the opposite side as shown in Figure 2 (B). - Sustain a stretching for 60 seconds the end range of motion without pain. Fully breathe in and out with pursed lip. Then, return to staring position. - Stretching exercise will be performed 10 times/set, 1 set/day, 3 days/week, for 8 weeks - Why don't the researchers use two-way repeated measures ANOVA instead of two-way ANOVA for the three outcome measurement periods? We have revised our analysis to use two-way repeated measures ANOVA for the three outcome measurement periods, as recommended. Results: - Page 7: What are \"the key results of the side measurements...\"? Because the figures show both within- and between-group findings, \"within-group comparison\" should be indicated in all figure captions. Discussion: - Please provide additional reasons why improvements in rounded shoulders, respiratory muscle strength, and scapulothoracic muscle flexibility and strength in COPD patients do not correlate with unchangeable lung function, dyspnea, and quality of life. Improvements in rounded shoulders, respiratory muscle strength, and scapulothoracic muscle flexibility and strength in COPD patients may not correlate with unchangeable lung function, dyspnea, and quality of life for several reasons: 1. Disease Pathophysiology: COPD is primarily characterized by irreversible airflow limitation due to chronic inflammation, alveolar destruction, and airway remodeling. While exercises can improve muscle strength and posture, they do not directly address the underlying structural damage to the lungs. 2. Nature of Lung Function Tests: Pulmonary function tests, such as FEV1 (Forced Expiratory Volume in one second) and FVC (Forced Vital Capacity), primarily measure the mechanical aspects of lung function, which are less likely to be influenced by changes in muscle strength or posture. These tests reflect the extent of airway obstruction and lung damage rather than the efficiency of respiratory muscles. 3. Dyspnea and Quality of Life Factors: Dyspnea (shortness of breath) and quality of life in COPD patients are influenced by a complex interplay of factors, including psychological aspects, overall physical conditioning, comorbidities, and the extent of lung damage. While improved muscle strength and posture can alleviate some symptoms, they may not be sufficient to significantly alter the overall perception of breathlessness and life quality. 4. Compensatory Mechanisms: COPD patients often develop compensatory mechanisms to cope with their condition, such as altered breathing patterns and muscle use. Improvements in muscle strength and posture might not be enough to overcome these established patterns and significantly change lung function or symptom perception. 5. Measurement Sensitivity: The tools used to measure lung function, dyspnea, and quality of life might not be sensitive enough to detect subtle changes resulting from exercise interventions. Improvements in muscle function and posture might contribute to better breathing mechanics and reduced symptoms, but these changes might not be captured by standard clinical assessments. 6. Multifactorial Nature of COPD: COPD affects multiple systems in the body, including the cardiovascular and muscular systems. While targeted exercises can improve specific aspects of physical function, comprehensive management involving medication, nutrition, and other interventions is necessary to achieve significant improvements in overall lung function, dyspnea, and quality of life. Therefore, while targeted exercises can lead to significant improvements in posture, muscle strength, and flexibility, the multifactorial and chronic nature of COPD means that these changes may not directly translate to improvements in lung function, dyspnea, and quality of life, which are influenced by a broader range of factors. References 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). (2023). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2023 Report). Retrieved from GOLD Website. 2. Dodd, J. E., Horne, J. M., & McKeon, C. (2020). “The effectiveness of exercise training in the management of chronic obstructive pulmonary disease: a systematic review.” Respiratory Medicine, 166, 105951. doi:10.1016/j.rmed.2020.105951. 3. Janssens, W., et al. (2019). \"The Impact of COPD on Quality of Life: The Role of Clinical and Psychological Factors.\" Chest, 155(5), 947-955. doi:10.1016/j.chest.2018.12.023. 4. Dixon, A. E., & Holguin, F. (2020). \"The importance of the musculoskeletal system in COPD: Why this matters.\" Thorax, 75(8), 649-651. doi:10.1136/thoraxjnl-2019-214911. 5. O'Donnell, D. E., et al. (2019). \"The effect of respiratory muscle training on dyspnea and quality of life in patients with COPD.\" Chest, 155(5), 1147-1156. doi:10.1016/j.chest.2019.01.014. 6. Gosselink, R., et al. (2021). \"Exercise training in patients with COPD: A review of the evidence.\" International Journal of Chronic Obstructive Pulmonary Disease, 16, 2231-2242. doi:10.2147/COPD.S307680. 7. Bourbeau, J., & Julien, D. (2021). \"Impact of COPD on patient’s quality of life.\" European Respiratory Review, 30(162), 210045. doi:10.1183/16000617.0045-2021. 8. Brady, S. L., et al. (2019). \"Effect of pulmonary rehabilitation on health-related quality of life in COPD: A systematic review and meta-analysis.\" Respiratory Care, 64(10), 1296-1305. doi:10.4187/respcare.06839. 9. Koulouris, N. G., & Makris, D. (2018). \"The role of respiratory muscle strength in chronic obstructive pulmonary disease.\" Breathe, 14(1), e24-e32. doi:10.1183/20734735.001418. 10. Palange, P., et al. (2020). \"Multidisciplinary approach to chronic obstructive pulmonary disease: Role of exercise training.\" Respiration, 99(7), 568-576. doi:10.1159/000504163."
}
]
},
{
"id": "243958",
"date": "29 Feb 2024",
"name": "Sonia Pawaria",
"expertise": [
"Reviewer Expertise Pulmonary Rehabilitation",
"Women Health",
"Renal 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 randomized controlled trial examined the effects of scapulothoracic exercises on male COPD patients with forward shoulder posture. Through a comprehensive assessment, including measures of chest mobility, respiratory muscle strength, and pulmonary function, the study aimed to elucidate the potential benefits of targeted interventions. Participants underwent a structured exercise regimen focusing on scapulothoracic region mobility and strength. The results revealed significant improvements in chest mobility, indicating enhanced thoracic expansion. Additionally, there were notable enhancements in respiratory muscle strength, suggesting improved respiratory efficiency. Pulmonary function assessments demonstrated favourable changes, with notable increases in vital capacity and forced expiratory volume. These findings underscore the potential of scapulothoracic exercises as an adjunct therapy for COPD patients with forward shoulder posture, offering a promising avenue for optimizing respiratory health and functional outcomes. However, further research is warranted to explore the long-term effects and optimal dosage of such interventions. I would like to acknowledge the commendable effort undertaken by the researchers in investigating posture correction strategies in COPD. Currently, pulmonary rehabilitation predominantly emphasises breathing retraining, making this exploration particularly significant.\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/11-1284
|
https://f1000research.com/articles/13-936/v1
|
20 Aug 24
|
{
"type": "Research Article",
"title": "Design, molecular docking, synthesis and in vitro evaluation of anti-influenza activity of oseltamivir carboxamides and their hybrid molecules with hydroxamic acid",
"authors": [
"Sumia Samer Tayah",
"Shakir Mahmood Alwan",
"Sumia Samer Tayah"
],
"abstract": "Background The influenza virus is a highly contagious respiratory disease that causes seasonal outbreaks and occasionally, unpredictable pandemics with high morbidity and mortality rates. This problem is exacerbated by the lack of drugs with potential antiviral activity against all types of influenza strains, including resistant strains. Therefore, there is an urgent need to develop novel antiviral agents.\n\nMethods The synthesis of new oseltamivir carboxamides with amino acids and the subsequent synthesis of hybrid molecules with hydroxamic acid were considered. Two series are presented as series one; oseltamivir carboxamides with L-serine, L-isoleucine, L-phenylalanine, L-tyrosine and series two included hydroxamates of series one. This approach may provide promising candidates with potential anti-influenza activity. The in vitro cytotoxic activity against Madin-Darby Canine Kidney (MDCK), type (NBL-2) - CCL-34 cells using the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to determine the half maximal inhibitory concentrations (IC50) of the investigated compounds. The percent inhibition of neuraminidase was plotted against concentrations and the IC50 values were calculated by non-linear logistic curve fitting.\n\nResults The compounds were subjected to molecular docking using the GOLD suite (version 5.7.1) to predict the binding affinities for neuraminidase (3CL0). The docking scores are presented as PLP fitness and are comparable to those of oseltamivir. Oseltamivir-Phenylalanine recorded the highest docking score (72.23 kcal/mol), while, oseltamivir acid was recorded (56.24 kcal/mol). The ADMET parameters were generated using the Swiss ADME server to predict successful candidates with reasonable oral absorption and safety margins. All compounds are safer than oseltamivir and their IC50 values for neuraminidase inhibition were variable. The hybrids showed a lower percentage of viable cells. Oseltamivir-phenylalanine had the highest inhibitory activity against neuraminidase (3.03 μM), when compared with oseltamivir (67.22 μM).\n\nConclusion Oseltamivir-phenylalanine showed remarkable and very significant activity, and the hybrid molecules were surprisingly less effective on neuraminidase than oseltamivir carboxamides.",
"keywords": [
"Oseltamivir",
"Hydroxamic acid",
"Molecular hybridization",
"Anti-influenza agents",
"Neuraminidase."
],
"content": "Introduction\n\nInfluenza viruses exert a significant threat to public health and are highly associated with variability and recombination.1–3 Certain known strains of the influenza virus usually mutate, and the genomic segments may undergo reassortment to produce new virus subtypes.4,5 Owing to the variable biochemical nature of viruses, the production of vaccines and synthesis of potential drugs is facing great challenges. Nevertheless, continuous potential research has led to the production of two main types of agents for the clinical treatment of influenza virus, such as, neuraminidase inhibitors (NAIs) and M2 channel ion blockers.6,7 NA inhibitors can weaken the release of influenza virus particles from infected cells, and effectively inhibit viral replication. The most potent representatives of NA inhibitors and FDA-Approved drugs include; Oseltamivir, Peramivir, and Zanamivir.8,9 Oseltamivir has been widely used in the treatment of influenza viruses and is a competitive inhibitor of NA.10,11 However, owing to the evolution of the influenza virus and the abuse of anti-influenza drugs, drug-resistant strains have emerged, such as H274Y/H1N1, which are the culprit leading to the H1N1 pandemic.11–13 Besides, the side effects of oseltamivir, such as inhibiting the production of viral antigens, leading to the reduction of acquired antiviral humoral immunity, and increasing the probability of re-infection have been recorded.14 Oseltamivir is a bulky molecule that cannot fit the active site of neuraminidase alone. However, it can bind to cavities 150 and 430, which induces a conformational change in neuraminidase, exposing the active site and allowing the oseltamivir molecule to bind to the active site and inhibit neuraminidase.15 NAIs that target cavities focus on designing molecules that can bind to both cavities with high affinity. This is a challenging task, as the two cavities are relatively small and hydrophobic.16 Several NAIs that target the cavities have been developed, and a number of the most promising candidates including Peramivir, Laninamivir octanoate, and Baloxavir marboxil are resistant to mutation.17,18 Certain amino acids have the potential to be employed as agents to facilitate targeted drug penetration and distribution. The solubility, stability and cellular penetration of antiviral agents can be enhanced through conjugation with amino acids, thereby, enhancing their delivery to infected cells.16 The enhanced biocompatibility of hybrid antiviral agents containing amino acids contributes to improved safety profile.19 The introduction of an amino acid substituent to the C1-carboxyl group of oseltamivir via an amide bond to afford carboxamides displayed greater potency.17 Histone deacetylases (HDACs) facilitate influenza virus replication by promoting chromatin condensation. The potential hindrance of viral genome replication can be achieved through inhibition of HDACs activity.13 Hydroxamate-based neuraminidase inhibitors function by structural mimicry, wherein they adopt configuration similar to that of sialic acid. The binding of a hydroxamate moiety to neuraminidase obstructs the active site of the enzyme, thereby, impeding its ability to cleave sialic acid residues. This mechanism inhibits the detachment of the virus from infected cells and impedes its propagation to adjacent cells.13,14 These inhibitors were designed to possess enhanced potency, a wider spectrum of activity, and reduced incidence of adverse effects.20 The molecular hybridization approach has been employed in the advancement of novel pharmaceuticals with enhanced efficacy, an expanded range of effectiveness and diminished adverse reactions.21\n\nIn view of previous investigations, an approach for synthesizing oseltamivir carboxamides with amino acids that may show better anti-influenza activity and probably enhance physicochemical properties is considered. L-serine and L-isoleucine, L-tryptophan and L-tyrosine are linked via amide bonds with oseltamivir carboxyl group. These carboxamides were also subjected to further reactions using hydroxylamine to afford the hydroxamates as molecular hybrids. These hydroxamates are expected to exert synergistic effects and, consequently, enhance the anti-influenza activity of oseltamivir.\n\n\nMethods\n\nOseltamivir phosphate (CAS No. 196618-13-0), L-tyrosine (CAS No. 60-18-4), L-isoleucine (CAS No. 73-32-5), L-serine (CAS No. 56-45-1), L-phenylalanine (CAS No. 63-91-2) and hydroxylamine hydrochloride (CAS No. 5470-11-1) were purchased from Sigma/Aldrich (St. Louis, MO, USA). Triethylamine (CAS No. 121-44-8) and dimethylsulphoxide (DMSO, CAS No. 67-68-5) were obtained from BDH (India). MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Influenza Neuraminidase Inhibitor Susceptibility Assay Kit (ab283398/abcam/USA). http://www.abcam.com/ab283398.\n\nThe melting points were determined using an electrical melting point apparatus (Electro-thermal 9300, USA). Infrared spectra were recorded on a (KBr disk) using an FT-IR spectrophotometer (Shimadzu 8400). 1H-NMR spectra were recorded using a Bruker 500 MHz spectrophotometer and 13C-NMR spectra (Avance III, 75.65 MHz spectrophotometer) were recorded using dimethylsulphoxide (DMSO-d6) as the solvent (5 mL). Chemical shifts were recorded in parts per million (ppm). Tetramethylsilane (TMS) was used as an internal reference. In vitro cytotoxicity assay was performed using the MTT colorimetric assay. The MTT assay is the first rapid colorimetric assay developed for cell viability with high screening in a 96-well format. This assay measures the reduction of yellow MTT to an insoluble blue formazan product by mitochondrial succinate. Neuraminidase inhibitor susceptibility tests were conducted using the Influenza Neuraminidase Inhibitor Susceptibility Assay Kit to evaluate the activities of the investigated compounds.\n\n\nComputational methods\n\nADME parameters and drug-likeness were determined using Swiss ADME (server). Lipinski’s rule of five holds substantial importance in the preclinical stage of pharmaceutical development and was used to predict the molecular properties of the investigated compounds.\n\nThe chemical structures of the compounds were depicted using ChemDraw Professional software (version 19.0) and energy minimization was performed using the MM2 force field. The structure of the neuraminidase enzyme was retrieved from the Protein Data Bank (PDB code: 3CL0).\n\nMolecular docking was performed using Hermes software (2021.2.0), an integral part of the CCDC GOLD suite. The ligand selected for the docking procedure included all protein residues situated within a 10 Å radius of the binding site on the protein. The determination of a fitness score is based on docking performance as assessed by the GOLD algorithm. The level of fitness is positively correlated with the strength of the docking interaction between the protein and ligand. Discovery Studio (2021) was used to create a 3D view (H-bonding cavity) and 2D view of the selected results (poses) of the docking process. The docking scores of the oseltamivir carboxamides and their hydroxamate molecules were recorded.\n\n\nChemical syntheses\n\nA mixture of an amino acid (0.01 mole, L-phenyl alanine, L-tyrosine, L-serine or L-isoleucine) and oseltamivir phosphate (0.01 mole) in absolute ethanol (30 mL) containing sodium hydroxide (5%) was continuously stirred and refluxed for 7 h. The mixture was cooled, poured into cold water (100 mL) and neutralized with diluted hydrochloric acid to pH 6. The solid product was collected and crystallized in ethanol: water (3:7). Chemical structures of the synthesized compounds were confirmed by spectral analyses (FT-IR, 1H-NMR and 13C-NMR). Details are provided in data availability.\n\nOseltamivir-Phenylalanine (2-({[4-(acetylamino)-5-amino-3-(pentane-2-aryloxy) cyclohex-1-en-1-yl] carbonyl} amino)-3-phenylpropanoic acid) was synthesized using oseltamivir phosphate (0.01 mole, 4.08g) and L-phenylalanine (0.01 mole, 1.65g), as previously described.\n\nOseltamivir-Isoleucine (2-(4-acetamido-5-amino-3-(pentan-3-yl) oxy) cyclohex-1-ene-1-carboxamido)-3-methylpentanoic acid) was synthesized using oseltamivir phosphate (0.01 mole, 4.08g) and L-Isoleucine (0.01 mole, 1.17g), as previously described.\n\nOseltamivir-Serine (2-({[4-(acetylamino)-5-amino-3-(pentane-2-aryloxy) cyclohex-1-en-1-yl] carbonyl} amino)-3-propanoic acid) was synthesized using oseltamivir phosphate (0.01 mole, 4.08g) and L-serine (0.01 mole, 1.05g), as previously described.\n\nOseltamivir-Tyrosine (2-({[4-(acetylamino)-5-amino-3-(pentan-2-yloxy) cyclohex-1-en-1-yl] carbonyl} amino)-3-(4-hydroxyphenyl) propanoic acid) was synthesized using oseltamivir phosphate (0.01 mole, 4.08g) and L-tyrosine (0.01 mole, 1.81g), as previously described.\n\nA mixture of oseltamivir carboxamides (1 mM) and zinc dust (0.5 g) in dioxane (30 mL), triethylamine (1 mM) and hydroxylamine hydrochloride (1 mM) was stirred continuously and refluxed for 2 h. The reaction mixture was filtered and carefully poured into cold water (100 mL) with continuous stirring. A crystalline powder was formed, separated by filtration and recrystallized from dioxane: water (3:7). Chemical structures were confirmed by spectral analyses (FT-IR, 1H-NMR and 13C-NMR). Details are provided in data availability.\n\nOseltamivir-Phenylalanine (1 mM, 0.431 g) and zinc dust (0.5 g) in dioxane (30 mL) containing TEA (1 mM, 1.2 mL) and hydroxylamine hydrochloride (1 mM, 0.069 g) were treated as previously described to obtain Os-Phe-hydroxamate.\n\nOseltamivir-Isoleucine (1 mM, 0.383 g) and zinc dust (0.5 g) in dioxane (30 mL) containing TEA (1 mM, 1.2 mL) hydroxylamine hydrochloride (1 mM, 0.069 g) and treated as previously described to afford Os-Ile-hydroxamate.\n\nOseltamivir-Serine (1 mM, 0.385 g) and zinc dust (0.5 g) in dioxane (30 mL) containing TEA (1 mM, 1.2 mL) and hydroxylamine hydrochloride (1 mM, 0.069 g) were continuously stirred and treated as previously described to afford Os-Ser-hydroxamate.\n\nOseltamivir-Tyrosine (1 mM, 0.447 g) and zinc dust (0.5 g) in dioxane (30 mL) containing TEA (1 mM, 1.2 mL) and hydroxylamine hydrochloride (1 mM, 0.069 g) mixture were treated as previously described to afford Os-Tyr-hydroxamate.\n\nThe cytotoxicity assay was performed using the MTT colorimetric assay22 and the effects of the synthesized compounds were evaluated in the MDCK cell lines.\n\nMDCK cells were purchased from the American Type Culture Collection (ATCC) and cultured in high-glucose Dulbecco’s modified Eagle’s medium (DMEM). Media were supplemented with heated fetal bovine serum (10%), L-glutamine (1%, 2 mM) and penicillin (100 IU/mL)/streptomycin (100 μg/ml) from (Euro Clone). The cell growth profile was seeded in a 96-well plate at a density of 6×104 cells/well and cell viability was determined by trypan blue exclusion using a haemocytometer.\n\nMDCK Cells were washed with phosphate-buffered saline (PBS) and detached with 0.025% trypsin-EDTA (Euro Clone), and media was added to a volume of 10 ml. The cell suspension was centrifuged at 1000 rpm for 10 min, and the pellets were re-suspended in 10 ml medium to make a single cell suspension. Cell viability was determined by trypan blue exclusion, which exceeded 90% as counted by a haemocytometer. The cells suspension was diluted to obtain the optimal seeding density, and 100 μl aliquot was placed in a 96-well plate. The cells were cultured at 37°C in a humidified atmosphere of 5% CO2, incubated for 24 h and then treated with different concentrations of each compound starting from 10mM (dissolved in DMSO, 5 mL) in a serial dilution manner (10, 5, 2.5, 1.25, 0.62, 0.31, 0.15 and 0.078 mM) and further incubated for 72h to determine the IC50 values. Cell growth was analyzed using the MTT colorimetric assay at the end of the exposure time.\n\nThe newly synthesized compounds were tested for the cell viability using an MTT colorimetric assay.22 MTT stock solution (15 μl, 5 mg/ml) in sterile PBS (pH 7.4) was incubated for 72 h and placed in each well. The cells were then added to each well and incubated for a further 3 h in the presence of a solubilizing stop solution (100 μL) to solubilize the dark violet formazan crystals. The optical density was measured at 570 nm using a microplate reader. The results are expressed as the percentage of cell viability compared with the control, corresponding to untreated cells.\n\nThe IC50 values for the investigated compounds were determined by constructing a dose-response curve.23 In the MTT assay, IC50 values denote the concentrations of compounds necessary to achieve a 50% reduction in cell viability. Based on the acquired data, the IC50 values were determined after a 72 h of exposure of the cells to the tested compounds. To ascertain the IC50 values, a concentration range consisting of the following concentrations (10-0.078 μM) was used.\n\nDetermination of the appropriate dilution factor for H1N1 viral strain\n\n4-Methylumbeliferone (4-MU) was used as a standard and by diluting the stock solution (5 mM, 10 μL) to neuraminidase assay buffer (990 μL) to obtain the working solution (50 μM). Using the compounds at concentrations (0, 0.1, 0.2, 0.4, 0.8, 1.2, 1.6 and 2.0 nM/well) and the 4-MU standard was prepared by adding 0, 2, 4, 8, 16, 24, 32 and 40 μL of the 50 μM solution into a series of wells, and the volume was adjusted for each well to 100 μL with neuraminidase assay buffer. Neuraminidase Stop Solution (100 μL) was added to each well (final volume of 200 μL/well) and mixed thoroughly. The fluorescence of the solution in the wells was measured at Ex/Em = 368/460 nm, the 0 nM/well (RFU) reading was subtracted from all of the standard readings, and the slope of the 4-MU standard curve was constructed. A series of 12 reaction wells from the H1N1 viral strain (one row of a 96-blanck well plate) was prepared by adding neuraminidase assay buffer (50 μL) to each well in columns 1-12. Fifty microliters of undiluted H1N1 viral isolate were added to column 1 and mixed thoroughly. A series of 2-fold serial dilutions were performed across the row of wells by transferring 50 μL from column 1 to column 2 and mixing the contents, until column 11 was reached. Fifty microliters from column 11 were discarded, leaving column 12 to serve as a background control well (no virus) to correct for non-enzymatic substrate hydrolysis. The volume of each well was 50 μl. The (96-dark well plate) was incubated at 37°C for 10 min to equilibrate the contents of the wells to the reaction temperature. During incubation, a concentrated neuraminidase substrate working solution (2X) was prepared by diluting the reconstituted neuraminidase substrate stock solution (100X) with neuraminidase assay buffer at a 1:50 ratio. Neuraminidase substrate solution (50 μl, 2X) was added to each reaction well, and the volume was brought to 100 μL/well. The plates were incubated at 37°C for 60 min in the dark. The reaction was terminated by addition of Neuraminidase Stop Solution (100 μL) to each well. The contents were thoroughly mixed and the fluorescence of the solutions was measured at Ex/Em= 368/460 nm.\n\nDetermination of the dilution factor corresponds to the RFU value\n\nThe fluorescence (F) was quantified by subtracting the mean fluorescence intensity of the solution containing no virus background control wells (RFU blank) from the fluorescence intensity of each sample well (RFU sample): F = RFU sample – RFU blank.\n\nFor the H1N1 viral strain, background-subtracted F values were plotted against the sample dilution factor. This value was used as the viral dilution factor in the inhibitor susceptibility assay.\n\nA set protocol was used to evaluate NA susceptibility, as follows; each tested compound was dissolved in DMSO solvent at final concentrations of less than (2%, v/v) to produce a master stock solution (10 mM). Working solution (1 mM) was prepared by diluting the master stock with neuraminidase assay buffer at a 1:10 ratio. The working solutions (4X) were prepared in a range of concentrations by diluting the working solution in neuraminidase assay buffer (to generate a multi-point dose-response curve) and to determine IC50 values for each compound. A series of working solutions (ten, 4X) were prepared in neuraminidase assay buffer (0.04, 0.2, 0.4, 2, 4, 20, 40, 400, 4000, and 40000 nM, corresponding to a final concentration range of 1 μM to 10 μM). H1N1 viral strain to be tested for susceptibility, a series of reaction wells were prepared containing 25 μL of each 4X test concentration (working solution) as well as the corresponding no-inhibitor control (containing neuraminidase assay buffer, 25 μL) and background control wells (containing 50 μL neuraminidase assay buffer). The H1N1 viral isolate stock solution was diluted with neuraminidase assay buffer according to the optimal dilution factor determined in the neuraminidase activity viral titration assay. The plate was incubated at 37°C for 30 min to allow the inhibitors to interact with the viral enzymes. During the incubation, a concentrated neuraminidase substrate working solution (2X) was prepared by diluting the reconstituted neuraminidase substrate stock solution (100X) with Neuraminidase assay buffer at a 1:50 ratio. A neuraminidase substrate solution (50 μL, 2X) was prepared for each well.24\n\nThe reaction was started by adding a neuraminidase substrate working solution (50 μL, 2X) to each reaction well, bringing the volume to 100 μl/well. The plates were incubated at 37°C for 60 min in the dark. The reaction was terminated by adding a neuraminidase stop solution (100 μL) to each well. The contents were mixed thoroughly and the fluorescence of all wells was measured at Ex/Em = 368/460 nm. For each reaction well, including no inhibitor/vehicle controls, the fluorescence intensity of the background control well (RFU blank) was subtracted to determine the background-corrected fluorescence (denoted by F). For each NI test concentration (FNI) in the dose-response curve, the percent inhibition (or remaining activity) relative to the vehicle control (FVC) was calculated using the following equation:\n\nThe relative activity (or percent inhibition) at each NI concentration was plotted and the IC50 values were calculated by non-linear logistic curve fitting.\n\n\nResults & discussion\n\nAll oseltamivir carboxamides with amino acids showed higher PLP fitness than that of oseltamivir acid. Os-Phe had the highest PLP fitness (72.228), while, Os-Ile had the lowest PLP fitness (59.142), when compared with oseltamivir acid (PLP fitness 56.241). The docking scores are listed in Table 1. The basic chemical structures of the target oseltamivir carboxamides include the potential pharmacophore of an oseltamivir ring containing a free carboxyl group, which is essential for its activity. Therefore, the interaction of these target compounds and oseltamivir with the amino acids of the enzyme is expected to be the same, as illustrated in Table 1, which is why the docking scores or PLP fitness scores showed great similarity.\n\nThe interaction of Os-Phe and its hybrid with hydroxamic acid and oseltamivir on N1 influenza neuraminidase enzyme type 3CLO is presented as 2D and 3D binding maps (Figures 1, 2, 3). The amino acids involved in the interaction of these compounds with neuraminidase indicated somewhat strong binding, as the binding was with several amino acids (Table 1). All compounds have the same binding requirements to reflect their activities and show higher affinity to the target protein. The 3D binding maps show the ability of the compounds to bind to cavities 150 and 430, while oseltamivir binding is restricted to cavity 150, which may reflect the higher PLP fitness of the synthesized target compounds compared to oseltamivir. It was obvious that the interaction of oseltamivir and its carboxamides and the hybrid molecules with hydroxamic acid occurred with the very basic amino acid, arginine at various positions (Table 1). This is probably due to the presence of the free carboxyl group of the oseltamivir ring, the amide in its carboxamides and the hydroxamate groups in the hybrid molecules. All the above groups are acidic in nature and interact with the basic arginine residues of the enzyme.\n\nThe molecular properties of the investigated target compounds were calculated based on Lipinski’s rule and its components.25 Lipophilicity (miLogP) and the total polar surface area (TPSA) values are essential factors for predicting the oral bioavailability of drugs.26 TPSA is a very useful descriptor used to characterize drug absorption and bioavailability, permeability through Caco-2 cells and transport across blood brain barrier.26 Higher values for TPSA and OH-NH interactions indicate that these compounds may have smooth and efficient binding to receptors. The recorded TPSA for all synthesized target compounds were higher than that of oseltamivir, indicating the possibility of potent binding affinity to the target enzyme. This may explain the higher docking scores obtained for oseltamivir acid (Tables 1 and 2). However, drug molecules with TPSA values of 140 Å or higher are expected to exhibit very low absorption.27 The ADME parameters of the new oseltamivir carboxamides and their hybrid molecules were measured to predict the possibility of oral absorption and reveal the safety of selecting the potential candidate(s). Os-Phe and Os-Ile have TPSA values of 132.75 and were predicted to have good permeability and GI absorption. Compounds Os-Phe, Os-Phe-hydroxamate, Os-Tyr and Os-Ile and oseltamivir acid showed higher lipophilicity values, which may be due to the hydrophobic groups present in their chemical structures (Table 2). All the synthesized target compounds showed no violation of the Lipinski rule of five, except for compounds Os-Ser-hydroxamate and Os-Tyr-hydroxamate, which may be due to the presence of hydroxyl groups at both amino acid side chains in serine and tyrosine. These violations were recorded for the H-donor and H-acceptor values. The BOILED-EGG, a graphical representation of all the calculations performed in order to forecast two crucial ADME parameters; passive absorption from the gastrointestinal tract (GIT) and access to the brain across the blood-brain barrier (details are found in data availability). The target compounds had a bioavailability score of 0.55, indicating that all compounds may enter the systemic circulation, as presented for Os-Phe and its hydroxamate derivative. Oseltamivir and the investigated compounds showed no penetration through the BBB, and may be considered Pgp substrates. The investigated compounds and oseltamivir were not Cytochrome P enzymes inhibitors, as tested for the following types Cyp1A2, Cyp2C19, Cyp2C9, Cyp2D6 and Cyp3A4.\n\nThe synthetic procedures for the target compounds is illustrated in Scheme 1. The basic principle of these methods is the synthesis of oseltamivir carboxamides with certain amino acids using a simple and effective procedure with appreciably high yields, which is an ester aminolysis reaction, as previously described. The most acceptable mechanism for these reactions is shown in Scheme 1. Oseltamivir carboxamides are converted to hybrid molecules by further reaction with hydroxylamine to afford oseltamivir-amino acid hydroxamates. The characterization and physical properties of the target compounds are presented in Table 3.\n\nThe proposed chemical structures of the synthesized compounds were confirmed by spectral analyses (FT-IR, 1H-NMR, 13C-NMR), as illustrated in Table 4 (details are listed in data availability).\n\nThe half maximal inhibitory concentrations (IC50 μM) of the investigated compounds on MDCK cells were compared to those of oseltamivir and the findings are presented in Table 5.\n\nAll oseltamivir carboxamides showed less cytotoxic activity and an excellent safety margin (Table 5). However, hybrid molecules of oseltamivir-amino acids-hydroxamates showed higher cytotoxic activity than oseltamivir (1490.5). This is an expected result, as the linkage of amino acids to certain drugs has been shown to afford much better conjugates in terms of activity, membrane penetrations, and enhanced physicochemical properties.17,19\n\nStatistical calculations of the results were conducted using Microsoft Office-Excel, and Figure 4 depicts the dose-response curves for IC50 values of the investigated compounds.\n\nThe in vitro cytotoxic activity against MDCK cell lines was used to determine the comparative cell viability percentage in relation to oseltamivir over 72 h of incubation. The percentage viability of oseltamivir carboxamides was comparable to that of oseltamivir, indicating great similarity with an acceptable safety margin. However, oseltamivir carboxamide-hydroxamates showed a much lower percentages of viable cells. At high concentrations (5000, 2500, and 1250 μg/ml) oseltamivir and its carboxamides with L-tyrosine, L-phenylalanine, L-isoleucine and L-serine had moderately high percentages of viability (72.45-94.04 μg/ml) indicating their moderate safety margin. Moreover, at a lower concentration of 156 μg/ml of all the investigated compounds including, oseltamivir, the percentage of viability was comparable and recorded very high percentages approaching 98% and above (details are listed on data availability).\n\nThe in vitro evaluation of anti-influenza activity, represented as the percent inhibition (or remaining activity) of neuraminidase at each concentration, was plotted to calculate the IC50 values by non-linear logistic curve fitting (Figure 4). The results revealed that there was a great variation in the activity of the investigated compounds of series one and two. Os-Phe exhibited the highest and most remarkable activity. This may be due to the presence of an aromatic ring of phenylalanine on the side chain, which may have contributed to the binding affinity, and consequently, enhanced the activity. However, Os-Tyr did not show appreciable activity, which may be due to the presence of a phenolic hydroxyl group that may have shifted the binding of the ligand away from the active site of the enzyme. Moreover, Os-Ile showed very low inhibitory activity against neuraminidase (5060 μM), while, Os-Ile-hydroxamate showed much better activity (216.4 μM), although, it was still less than that of oseltamivir. Os-Phe showed better anti-influenza activity (3.03 μM) than oseltamivir activity (67.22 μM). However, the hybrid molecule, which is Os-Phe-Hydroxamate recorded an activity approaching 430 μM, which is less active than Os-Phe (3.03 μM) and oseltamivir (67.22 μM). Oseltamivir-amino acid-hydroxamates were less active than oseltamivir carboxamides or oseltamivir. This may indicate that these hybrid molecules have activity on HDACs enzymes and not on the neuraminidase of influenza. This case definitely requires further investigation to evaluate their activities on HDACs, as inhibitors. This possibility cannot be ruled out. It is quite obvious that aliphatic amino acids did not contribute to activity, and hence, the IC50 values of Os-Ile, Os-Ser, and their hydroxamates were very poor and recorded much higher IC50 values. Similar results were obtained for oseltamivir carboxamides with alanine and glycine.28 Interestingly, oseltamivir carboxamide with D-valine, exerted high potency against neuraminidase of H5N1 and H5N6. The inhibitory potency of NA may be ascribed to the retention of the carboxylate group and the presence of a hydrophobic isopropyl group. However, the incorporation of alanine or glycine did not improve activity.28 Similarly, in the present study, oseltamivir carboxamides with L-serine and L-isoleucine did not show appreciable activity for not a clear reason, when compared with the active oseltamivir carboxamide with D-valine, as mentioned earlier. Apparently, the presence of a free carboxyl group or its isostere, such as an amide, on the ring structure of oseltamivir is important for the inhibition of neuraminidase to afford an anti-influenza activity. A similar finding of improved activity was established for oseltamivir carboxamides with various amines.28 The active site or loops of neuraminidase are large enough to accommodate an inhibitor with reasonable activity.15 Amino acids possessing aromatic or cationic side chains have the ability to engage in interactions with viral proteins or nucleic acids, so impeding viral reproduction.29 Incorporation of aromatic amino acids within certain cephalosporin have proved effective in enhancing the binding affinity of the parent molecules leading to an increase in activity.30 Synthesis of oseltamivir carboxamides has proved to be effective and retain activity and in certain cases, such as, aromatic amino acids enhanced the activity over the parent compound. This has also been observed in synthesizing new levofloxacin carboxamides with certain aromatic amino acids.31 Hydroxamate-derived compounds have demonstrated efficacy as neuraminidase inhibitors, rendering them presently employed in the treatment and prophylaxis of influenza infection.32 Oseltamivir-hydroxamates, containing a CONHOH group instead of a COOH group, exhibited a significant decrease in activity (> 40-fold) compared to the parent compound. The CONHOH group was not suitable for accommodating NA pocket. This pocket in the active site contains three basic residues, Arg 118, Arg 292, and Arg 371, which can strongly interact with acidic groups, such as a COOH32 or the phosphoryl group.33 It is not surprising that the above oseltamivir carboxamides32 revealed much weaker activity and this may be due to the lack of the linker side chain, and hence, does not fulfil the required structure-activity relationship (SAR) for the optimum activity. The required length is 4-6 atoms separating the cap group and the hydroxamate moiety. The proposed oseltamivir carboxamides containing aliphatic and aromatic amino acids in the side chain included in this study retain the full SAR requirement for optimum activity. Generally, the hydroxamate group, with an intramolecular hydrogen bond is weaker than COOH in acidity, which may have largely contributed to the poor activities of these compounds.\n\n\nConclusion\n\nTwo series of novel oseltamivir carboxamides and their hybrid molecules with hydroxamic acid were successfully synthesized and evaluated using in silico methods. The results showed that all compounds were highly absorbed via passive diffusion through the gastrointestinal tract and comply with Lipinski’s rule of five, except Os-Ser-Hydroxamate and Os-Tyr-hydroxamate with one violation for each. The in vitro evaluation of anti-influenza activity revealed that there was a great variation in the activity of the investigated compounds in both series one and two. Os-Phe exhibited the highest and most remarkable activity. Generally, oseltamivir-amino acids-hydroxamates are less active than oseltamivir carboxamides or oseltamivir.\n\n\nAuthor roles\n\nAlwan, S.M.: Project idea, supervision, data curation, formal analysis, acquisition, methodology and chemical synthesis, resources, visualization, writing – original draft preparation, review and editing. Tayah, S.S.: Formal analysis, methodology and chemical synthesis, in silico prediction, investigation, resources, validation, writing draft preparation.\n\n\nEthics\n\nEthical approval and consent was not required.",
"appendix": "Data availability\n\nMore information can be found in data availability, as separate files named for certain investigation including the DOI for each file. This project contains the following underlying data.\n\nZenodo: Underlying data;\n\nCharts of FT-IR Spectra: https://doi.org/10.5281/zenodo.11115384\n\n1H-NMR Spectra: https://doi.org/10.5281/zenodo.11115259\n\n13C-NMR Spectra: https://doi.org/10.5281/zenodo.11115354.\n\nADME Parameters: https://doi.org/10.5281/zenodo.11115404\n\nCytotoxicity Results: https://doi.org/10.5281/zenodo.11115420\n\nAntiviral Activity Results: https://doi.org/10.5281/zenodo.11115434.\n\nFigures 1-4: https://doi.org/10.5281/zenodo.11568013.\n\nDetailed description of all materials that are used in this study and the influenza neuraminidase inhibitor assay kit for performing the assay of activity of the investigated compounds are given in the underlying data.\n\nMaterials: https://doi.org/10.5281/zenodo.12679138.\n\nInfluenza neuraminidase inhibitor-assay kit: https://doi.org/10.5281/zenodo.11508406.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgment\n\nThe authors acknowledge and appreciate the support of the College of Pharmacy, Al-Mustansiriyah University and the Department of Pharmacy, Al-Farabi University College. The authors also acknowledge the efforts of the University of Jordan in performing the cytotoxicity and anti-influenza activity tests.\n\n\nReferences\n\nYu W, Cheng LP, Pang W, et al.: Design, synthesis and biological evaluation of novel 1, 3, 4-oxadiazole derivatives as potent neuraminidase inhibitors. Bioorg. Med. Chem. 2022, 1; 57: 116647. PubMed Abstract | Publisher Full Text\n\nLi M, Cheng LP, Pang W, et al.: Design, synthesis, and biological evaluation of novel acylhydrazone derivatives as potent neuraminidase inhibitors. ACS Med. Chem. Lett. 2020, 24; 11(9): 1745–1750. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYe J, Lin L, Xu J, et al.: Design, Synthesis, Biological Evaluation and in Silico Studies of Pyrazole-Based NH2-Acyl Oseltamivir Analogues as Potent Neuraminidase Inhibitors. Pharmaceuticals 2021, 16; 14(4): 371. 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}
|
[
{
"id": "327201",
"date": "28 Sep 2024",
"name": "Hasanain Odhar",
"expertise": [
"Reviewer Expertise Pharmacology",
"computational drug design",
"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\nThis is an interesting article that combine computational pharmacology, chemical synthesis and in vitro assessment. The authors have focused on the synthesis of several oseltamivir derivatives by conjugation to some amino acids. Further, they synthesized hybrid derivatives by using hydroxamic acid. The aim of this study was to enhance bioavailability, potency and spectrum of these new oseltamivir derivatives against neuraminidase enzyme. However, Authors have clearly present the used methods and associated results. However, I recommend the following minor revisions: 1- In the abstract, the aim of study should be clearly mentioned by end of background. 2- The two lines about GOLD docking software in the abstract results should be moved into methods part. 3- In the introduction, author should change \"FDA-Approved\" into \"FDA-approved\". 4- In the introduction, I am wondering how oseltamivir can increase risk of reinfection as authors mentioned. Further elaboration is required. 5- For the introduction, may be authors can present a figure that show how oseltamivir can bind into cavities 150 and 430. 6- In the introduction, authors may further explain how inhibition of HDAC enzyme is related to study subject. 7- In the methods, authors should mention website or appropriate reference to Swiss ADME. 8- The subsections of MTT assay and neuraminidase inhibition ELISA test should be restructured in a more clear style. 9- Authors are advised to present a higher images resolutions for 2D docking results (Discovery studio) so that amino acids names can be identified easily.\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": "12739",
"date": "31 Oct 2024",
"name": "shakir Alwan",
"role": "Author Response",
"response": "Response to reviewer 1 Add the following phrase at the end of background “An approach of synthesizing new oseltamivir derivatives with expected increase of bioavailability, potency and spectrum of activity is considered. It is ok with those two lines of docking. We may change FDA-Approved to FDA-approved. The case may increase the probability of re-infection and not oseltamivir. Reference 15 indicate and showed the binding of oseltamivir with the 150 and 430 cavities. This study includes synthesis of oseltamivir hydroxamates, which are well-known HDACs Inhibitors. SwissADME server is an online free website. MTT colorimetric test is a well-known method and was written according to actual procedure acquired by the lab. Images of interactions of compounds with target site are clear enough to be read."
}
]
}
] | 1
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https://f1000research.com/articles/13-936
|
https://f1000research.com/articles/13-544/v1
|
28 May 24
|
{
"type": "Research Article",
"title": "Exploring the acceptance of robotic assisted surgery among the Indian population: An empirical investigation",
"authors": [
"Smitha Nayak",
"Vinod C. Nayak",
"Sathvika G. S.",
"Smitha Nayak",
"Sathvika G. S."
],
"abstract": "Background Technology has completely transformed healthcare, starting with X-ray machines and MRIs to telehealth and robotic surgeries to e-health records. The launch of minimally invasive surgery (MIS) serves as a milestone in medical history, offering benefits such as smaller incisions, shorter hospital stays, and faster recovery, making it a preferred surgical option. This study mainly explores patients’ willingness to adopt robot-assisted surgery (RAS) technology in a surgical intervention and is assessed in the backdrop of the Technology Acceptance Model (TAM).\n\nMethods This research project employs a post-positivist research philosophy and a cross-sectional research design. A structured, pre-tested questionnaire was used to collect data from 280 respondents.\n\nResults The results revealed that trust had a significant impact on Perceived Usefulness (β = 0.099) and Perceived Ease of Use (β = .157), and eHealth literacy had a significant impact on Perceived Ease of Use (β = 0.438) and Perceived Usefulness (β = 0.454). Additionally, Perceived Usefulness partially influenced behavioral intention (β = 0.123), and attitude had a significant influence on behavioral intention (β = 0.612). The analysis revealed an insignificant impact of eHealth literacy on Perceived Usefulness (β = 0.067). The Standard Root Mean Square Residual (SRMR) value was <0.8. Mediation analysis also revealed partial mediation between the constructs. The SRMR rating of this model is 0.067, indicating that it fits the data well.\n\nConclusion This study revealed that a patient's intention will be high if he or she believes that RAS is beneficial in treating his or her ailment. In comparison, information related to RAS is clearly known, and it does not directly affect selection intention. eHealth literacy is a significant antecedent to patients’ behavioral intention. Hence, the healthcare industry must devise strategies to promote the acceptance of RAS at all levels.",
"keywords": [
"robotic-assisted surgery",
"technology acceptance model",
"eHealth Literacy",
"intention",
"mediation"
],
"content": "Introduction\n\nSince its inception, technology has gradually merged with the medical industry. Beginning with inventions like x-ray machines and MRIs and expanding to include telehealth, robotic surgery, and electronic health data, it has radically transformed healthcare. Technology has become an essential component of the medical industry and is responsible for patient diagnosis, treatment, and data administration. The substantial impact of technology on surgical techniques has caused a significant revolution in the field of medicine. Modern technology has improved patient outcomes (Kim et al., 2017), increased precision, decreased invasiveness, and increased the number of therapeutic alternatives (Prasad, 2013).\n\nTechnological advancements in surgery have also been embraced. The launch of minimally invasive surgery (MIS) has served as a milestone in medical history, offering benefits such as shorter hospital stays, minor incisions, and faster recovery, making it a preferred surgical option (Irani et al., 2016). Further technological advancements in MIS have led to the evolution of robotic-assisted surgeons (RAS), which have displayed tremendous advantages to the economy, healthcare system, doctors, and patients (Bora et al., 2020).\n\nThe All India Institute of Medical Sciences, New Delhi, received India's first urologic robotic installation in 2006, following the US FDA's approval of the da Vinci system in 2000. Over the next 10 years, robotic surgery in India has seen unprecedented progress. As of July 2019, our country had 66 facilities, 71 robotic installations, and more than 500 skilled robotic surgeons. Over the past 12 years, more than 12,800 surgeries have been performed with robotic assistance (Bora et al., 2020). As per this trend, RAS is expected to expand in India and revolutionize the healthcare system.\n\nEven though there is an increasing trend in the number of RAS globally (Xue & Liu, 2022) and in India, research reveals that patients’ perceptions of RAS are unclear. Research undertaken by Irani et al. (2016) revealed that 34 percent of the participants had a vague understanding of the differences between laparoscopic and open surgery. Furthermore, 46 percent of the participants were not clear regarding the differences between laparoscopic intervention and RAS. Inconsistency in patients’ awareness of the modes of technological interventions was also observed in another study undertaken among female gynecological patients, and Ahn et al. (2014). Similar research findings have been documented by Ammer et al. (2022) and Chan et al. (2022). Differences in understanding and acceptance of RAS were also observed between genders (McDermott et al. 2020).\n\nThere has been an increased focus on the co-production of health, because health outcomes are influenced by a complex interplay between physicians, patients, and healthcare systems, rather than being solely determined by medical staff or hospitals (Puja Turakhia, 2017). There is a need to ensure that patients make informed decisions, which the healthcare system is bound to facilitate. Knowledge of patient preferences and awareness are needed to create an ecosystem that facilitates patients to make informed decisions. This is of paramount importance in the context of RAS and LS, as despite research evidence on the benefits of these interventions, they have gained poor patient acceptance. This could be attributed to the apprehensions that technology has created among patients who traditionally view healthcare as isolated from technology (Buabbas et al., 2020). Against this backdrop, it is important to explore the factors that would explain patients’ intentions to adopt RAS or LS.\n\nThe Technology Acceptance Model (TAM) proposed by Davis (1989) serves as the theoretical underpinning for this research endeavor. The “Technology Acceptance Model” (TAM), which sheds light on the crucial roles of perceived usefulness and ease of use in influencing an individual's tendency towards embracing emerging technological breakthroughs, forms an essential component in understanding the dynamics of technology adoption. The importance of TAM lies in its simple explanation of how a person's assessment of a technology's prospective advantages and how user-friendly it is has a significant impact on their preparedness to interact with and employ new technological tools. TAM provides helpful insights into developing and directing the development of user-centric technologies that connect with users and pave the way for their effective adoption and integration into their lives by highlighting the underlying interplay between these aspects. Research has shown (Xie et al., 2022; Xu et al., 2021) demonstrates a positive influence of eHealth literacy among patients on health outcomes.\n\nA new era has begun in India, thanks to the quick and broad adoption of the Internet, which has given the populace unparalleled access to a massive library of health-related knowledge (Parija et al., 2020). The increase in digital connectedness has been crucial in enabling people to make wise choices regarding their health and well-being. People throughout the country can now easily access a multitude of medical information, from symptoms and treatments to health tips and preventive measures. In addition to raising awareness, the democratization of health information has made it possible for people to actively participate in their healthcare, have informed conversations with healthcare professionals, and promote their well-being. Thus, the Internet’s quick spread has shown to be an effective catalyst for creating a culture in which people are empowered to take control of their health through informed decision-making. Finding reliable and accurate insights from a sea of knowledge requires a detailed eye. People are more likely to make wise health decisions when they have access to digital literacy (McCray, 2004). Hence, to ascertain the population’s ability to obtain and utilize health information, this research endeavor has integrated eHealth literacy (Norman & Skinner, 2006) into the conceptual framework (Figure 1).\n\nThe healthcare environment is significantly shaped by patient trust in doctors, which has implications for patient happiness and medical outcomes. The development of an effective doctor-patient trust connection is important for improving treatment adherence, increasing patient engagement, and eventually improving health outcomes (Hall et al., 2001). Therefore, fostering and preserving patient trust serves as the foundation for efficient and patient-centered medical treatment in an era characterized by increased patient empowerment and information availability (Krot & Rudawska, 2016). Hence, the patient's trust in the doctor is included as an external construct in the TAM to explore its influence on a person’s intention to opt for RAS. We explored whether patients' trust in the physician influences their beliefs about perceived ease of use and perceived usefulness of RAS.\n\n\nMethods\n\nThis research endeavor was quantitative and used a cross-sectional research methodology. \"Post-positivism\" is the research philosophy that was taken into account in this study; it deals with the development of empirical approaches to understanding and exploring human behavior. This study considered that surgeons with RAS training would perform the surgery and was founded on a thorough examination of the literature and the theoretical underpinnings of the TAM (Davis, 1989). Therefore, trust was included as an antecedent in this study. This new era of digital evolution has enhanced e-health literacy, enabling patients to make informed health decisions. Hence, e-health literacy was incorporated into this framework to assess its influence on attitudes towards and intention to adopt RAS.\n\nThere is significant research confirmation indicating a compelling association between lower socioeconomic status and health literacy, healthcare use, and health outcomes (Diez Roux, 2012). This research study was undertaken in Bangalore Urban, Udupi, and Dakshina districts of Karnataka state in India, which are ranked in the top three based on the “Human Development Index Report” published by the Government of Karnataka. Purposive sampling was used to enroll participants from various backgrounds to explore their perceptions of the RAS. Participants were recruited only if they were older than 18 years of age and knew English. Snowball sampling was used to recruit the participants. Respondents were contacted in person and explained by the researchers the purpose of the study and assured that their data would only be used for academic purpose, and if they consented to participate in the survey orally, to the researcher, the questionnaire was given to them in hard copy or in soft copy format. The participants had two options. They could record their response in the hard copy of the questionnaire or using the Google form. As the participants had access to the internet and WhatsApp, all chose to record their responses using the Google form. Hence, the Google form link was shared with the participants, and they were requested to submit their responses. The estimated sample size was 260 (Hair Jr. et al., 2019). Data from 280 participants were collected for the study.\n\nThis marketing study was exempt from submission to the Institutional Ethics Committee of Manipal Academy of Higher Education as per clause 6 of the circular titled “Project exemption from submission to IEC” issued by the Institutional Ethical Committee dated 14/1/2021 and hence approval from the department level committee was obtained. Approval was obtained from the Department Review. Committee of the Department of Bio-Medical Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, India, on June 14th, 2023. Approval on the research gap, conceptual framework, scales to be adopted in the study and research design to be adopted to by the research team was obtained only after a detailed presentation and proposal submission. After this approval, the research project was implemented. A structured questionnaire was designed to capture the responses. The research instrument was divided into two sections. The first section documented the demographic details of the respondents and the second section captured responses on the research constructs (Perceived Usefulness (PU), Perceived Ease of Use (PEU), Trust, Attitude, Behavioural intention) adapted form (Kao et al., 2022) and eHealth Literacy Scale (eHLS) (van der Vaart et al., 2011). The participants’ responses in the second section were captured on a Likert scale, where 1= strongly disagree and 5 = strongly agree. Data were gathered from July 2023 to August 2023 (Nayak et al., 2023a,b). IBM SPSS Statistics 27 (RRID: SCR_016479; Armonk, NY: IBM Corp) was used to perform the descriptive analysis, and the results are presented in the subsequent section. SmartPLS 4 (RRID: SCR 022040) was used to evaluate the proposed hypotheses and perform the mediation analysis. Research Project completion approval was obtained from the department on August 15, 2023.\n\n\nResults\n\nA total of 280 individuals participated in the study, 126 of whom were men and 154 were women. Only 5% of the respondents had experienced RAS scenarios, while 43% had already undergone surgical operations. Notably, 70% of the participants were aware of RAS (Table 1).\n\nThe measurement model was assessed to establish the reliability and validity of the constructs (Table 2). In the structural model (Figure 2), the factor loading of the items was examined to ensure that they exceeded 0.5 (Hair et al., 2010). Although (Vinzi et al., 2010) recommended a minimum factor loading of 0.7, it has been noted that researchers frequently run into lower outer loadings in social science studies. It would be better to consider how the removal of indicators might impact the improvement of the reliability and validity of the constructs rather than doing so right away. Additionally, only if doing so increases composite dependability (Average Variance Extracted) above a certain threshold value can one consider deleting indicators with factor loadings ranging from 0.4 and 0.7 (Sarstedt et al., 2017). In the present study, eHLs1 (loading = 0.116) was eliminated because it was far below the threshold value.\n\n*** p<0.01.\n\n** <0.1.\n\nConstruct reliability and validity were established using Cronbach's alpha, rho_a, and composite reliability (Table 2). The computed rho_a value above the cutoff of 0.7 (Wasko & Faraj, 2005), which is a sign of strong reliability according to (Henseler et al., 2016), fell between the composite reliability as defined by (Sarstedt et al., 2017) and Cronbach's alpha. The “Average Variance Extracted” (AVE) value of more than 0.5 was required to show convergent validity. The Fornell and Larcker methodology was used to confirm discriminant validity in this research (Table 3).\n\nThe R2 and Q2 path coefficients obtained in the structural model enabled researchers to evaluate the proposed relationships within the research framework. The R2 establishes that the predictive capacity of the model should be above 0.1(Falk and Miller, 1992). Q2 determines the predictive relevance of the model and should be greater than 0. In the current model, both the R2 and Q2 values were above the threshold values, showing the effectiveness of the model (Table 4). \"Standard Root Mean Square Residual (SRMR) was used to measure model fitness. The threshold estimate of SRMR was <0.8 (Sarstedt et al., 2017). This model had a good fit for the data, as indicated by its SRMR value of 0.067. Furthermore, Q2 was calculated if the endogenous construct was more than zero; hence, predictive relevance was established.\n\n*** p<0.01.\n\n** <0.05.\n\n* <0.1.\n\nThe hypothesis-testing results are presented in Table 4. The results revealed that trust had a significant impact on PU (β = 0.099, t = 2.111, p = 0.035) and PeoU (β = .157, t = 3.107, p = 0.002). eHLt had a significant impact on PEoU (β = 0.438, t = 9.263, p = 0.000), and PEoU had a significant impact on PU (β = 0.454, t = 8.525, p = 0.000). PU (β = 0.611, t = 12.166, p = 0.000) and PEoU (β = 0.199, t = 2.323, p = 0.020) influenced attitude. PU partially influenced BI (β = 0.123, t = 2.159, p = 0.031) and attitude had a significant influence on BI (β = 0.612, t = 13.161, p = 0.000). The analysis revealed an insignificant impact of eHLt on Perceived Usefulness (β = 0.067, t = 1.064, p = 0.288).\n\nIn this study, two mediators were proposed and assessed. In the first case, mediation analysis was conducted to assess the mediating role of attitude towards RAS in the relationship between PU and BI (Table 5). The results revealed a complementary partial mediation of PU (β = 0.413, t = 9.579, p = 0.000) through RAS attitude on behavior intention. The effects of trust and eHLt on PU were assessed using the PEofU. Complementary patrial mediation was observed for trust in PU (β = 0.138, t = 4.162, p = 0.000) through PEoU. Full mediation was observed between eHLt and PU (Î2 = 0.230, t = 6.1919.579, p = 0.000) through PEoU.\n\nThe outcome of IPMA is presented as bootstrapping with 5,000 subsamples, demonstrating that some of the path coefficients are statistically significant and that all conditions for using the IPMA approach are satisfied. IPMA elucidates the relative significance and performance of exogenous (trust, eHLt, PU, PEoU, and Attitude) and endogenous constructs (behavior intention) about each other. Their significance and efficacy are shown by their aggregate impacts and index values. The impact on the endogenous variables is significant. The intrinsic potential of the latent variable scores is demonstrated through effectiveness. Along the X- and Y-axes, the significance and efficacy were quantified. The entire effect is shown on the x-axis, and the effectiveness is represented on the y-axis. A construct performed better when it had a higher mean value (Sarstedt et al., 2017). The results for the IMPA (Figure 3 and Table 6). All construct performances ranged from 50 to 70. Furthermore, Attitude (Importance = 0.612 Performance = 51.257), Perceived Usefulness (Importance = 0.498 Performance = 50.165), and Perceived Ease of Use (Importance = 0.299, Performance = 51.748) must be given priority as their importance and performance (Table 6, Figure 3).\n\n\nDiscussion and Conclusion\n\nThe results of this research suggest that patients' understanding of RAS information and subsequent decisions about medical procedures are influenced by the degree of trust they have developed with their doctors. “Trust” embedded in their relationship enables patients to comprehend the benefits of PEoU and PU of RAS and enables them to take a rational decision. This is in line with the research evidence presented by Yang & Wu (2018) and, Petrocchi et al. (2019) who state that a strong relationship between the healthcare service provider/doctor and patient strengthens health outcomes and enables the patient to make better-informed health decisions. In addition, eHLt was observed to significantly influence PEoU, which is in line with the results of previous studies McCray (2004); Kao et al. (2022); Yuan et al. (2022). The ease with which a person can use and understand Internet health information can have a significant impact on their perception of medical care. eHealth literate people are better able to obtain accurate and pertinent health information and make wise decisions regarding their well-being. This competency also improves patients' capacity to interact effectively with healthcare professionals, encouraging meaningful dialogue and group decision making. PEoU was observed to positively influence the PU of the RAS. It is evident from this result that if patients can clearly comprehend the benefits of RAS, it will enable them to determine the benefits themselves. The PU construct is borrowed and altered from Kao et al. (2022) and Davis (1989). The term originally refers to an information technology system that the user uses personally, and it states that user acceptance will grow for systems that are simple to use. However, in this case, it was a doctor managing RAS. Hence, the construct indicators were altered to suit the study for a better interpretation of the results. In addition, the findings demonstrate that there is no association between eHLt and PU of RAS, even if patients can easily acquire knowledge about RAS and comprehend its function. Although eHLt does not directly affect willingness to use, it still has an impact through PEoU. The impact of eHealth literacy on the PeoU of RAS has significant effects on the Indian population's acceptance and utilization of advanced medical technologies. In this context, eHealth literacy, which encompasses the ability to comprehend and navigate digital health information, is a critical factor in determining individuals' ability to appreciate and accept this mode of surgical intervention. The relationship between eHealth literacy and the perceived ease of use of robot-assisted surgery highlights the importance of tailored educational initiatives to equip people with awareness of RAS. The healthcare industry and its specialists should take advantage of India's extensive digital integration to raise awareness and encourage acceptance among the population. This proactive strategy could substantially impact how people view robot-assisted surgery (RAS), change their attitudes, and increase their willingness to opt for this technology.\n\nIt was also observed that PU indirectly influences BI through attitude, which is in line with previously documented literature (Kao et al. 2022; Beldad & Hegner, 2018; Horowitz & Kahn, 2021; Horowitz & Kahn, 2021). It is interesting to note that attitude towards RAS is a significant antecedent to BI; hence, building a positive attitude among the population is necessary for the adoption of RAS.\n\nIn conclusion, the use of Robot-Assisted Surgery (RAS) has increased noticeably recently and offers obvious advantages over traditional surgical techniques or endoscopic procedures, especially in complex surgeries at difficult anatomical sites. Since its introduction in India in 2006, a minimum of 12,800 surgeries have been successfully completed using RAS technology. Given the advantages of the RAS mode, the healthcare system should design and implement strategies to enhance awareness and, hence, acceptance among the Indian population. The penetration of the Internet in India has opened up a plethora of means for channelizing communication with the audience (AlMuammar et al., 2021). The healthcare system and healthcare professionals must use different forms of social media to educate the population on the benefits of RAS, enabling them to build a positive attitude toward RAS and, hence, BI. As documented by MINI Tejaswi (2021) RAS is gaining acceptance among patients and healthcare professionals in India, there is a need to further promote positive attitudes among the Indian population to build acceptance of RAS in India.\n\nThis study makes two contributions to the literature. Unlike earlier research that primarily concentrated on the efficiency of RAS surgical equipment, this study employed the TAM to evaluate the actions and intentions of RAS among the Indian population. According to this study, an individual's perceptions regarding whether they believe surgery would be useful or whether they have access to enough information to make informed decisions are influenced by their level of trust. In addition, this study aids in the investigation of variables influencing an individual's readiness to undergo sophisticated surgical procedures. This research also investigates the influence of eHLt, which is a significant antecedent to mold positive attitudes, thereby influencing their acceptance of RAS.\n\nDoctors play a crucial and essential role in successfully explaining the benefits of robotic-assisted surgery in patients. Beyond their medical knowledge, they play an important role in converting difficult technical information into clear and understandable language. Doctors may explain how robot-assisted surgery may improve surgical results, reduce invasiveness, speed up recovery, and improve patient experiences by having open and compassionate conversations with patients. This open communication encourages confidence and cooperation between healthcare professionals and patients being treated by them by empowering them to make knowledgeable healthcare decisions. Clinicians act as both advocates and educators, ensuring that patients understand the advantages of this novel surgical approach and may influence their care. This will strengthen the trust a patient displays in the doctor and, hence, influence their behavior.\n\nThe literature also identifies important criticisms, such as TAM's shortcomings in identifying issues outside of its purview, such as costs and underlying structural pressures driving users to adopt an invention. The continued adoption and evolution of TAM will depend on how well it is implemented in cutting-edge medical technologies. It is important to note that this early cross-sectional study did not account for differences among other medical specialties, which calls for attention in future research frameworks. Such frameworks could also compare and contrast the preferences and tendencies of patients who had prior experience with robotic surgery (RSS) and those who did not. Future research can provide more thorough insights, producing findings that more accurately reflect heterogeneous patient groups.",
"appendix": "Data availability\n\nFigshare: Figshare: Exploring the acceptance of robotic assisted surgery among the Indian population: An empirical investigation. https://doi.org/10.6084/m9.figshare.24131124.v1 (Nayak et al., 2023c)\n\nThis project contains the following underlying data:\n\n- Data file\n\nFigshare: RAS Paper. https://doi.org/10.6084/m9.figshare.25256833.v1 (Nayak et al., 2024)\n\nThis project contains the following extended data:\n\n- RAS_Questionnaire\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nAhn KH, Donnellan N, Lee TTM: Patient Perception of Robotic Surgery in Gynecology. J. Minim. Invasive Gynecol. 2014; 21(6): S71. Publisher Full Text\n\nAlMuammar SA, Noorsaeed AS, Alafif RA, et al.: The Use of Internet and Social Media for Health Information and Its Consequences Among the Population in Saudi Arabia. Cureus. 2021; 13: e18338. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmmer E, Mandt LS, Silbersdorff IC, et al.: Robotic Anxiety—Parents’ Perception of Robot-Assisted Pediatric Surgery. Children. 2022; 9(3): 399. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBeldad AD, Hegner SM: Expanding the Technology Acceptance Model with the Inclusion of Trust, Social Influence, and Health Valuation to Determine the Predictors of German Users’ Willingness to Continue using a Fitness App: A Structural Equation Modeling Approach. Int. J. Hum.-Comput. Interact. 2018; 34(9): 882–893. Publisher Full Text\n\nBora G, Narain T, Sharma A, et al.: Robot-assisted surgery in India: A SWOT analysis. Indian J. Urol. 2020; 36(1): 1–3. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBuabbas AJ, Aldousari S, Shehab AA: An exploratory study of public awareness about robotics-assisted surgery in Kuwait. BMC Med. Inform. Decis. Mak. 2020; 20(1): 140. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChan KS, Kwan JR, Shelat VG: Awareness, perception, knowledge, and attitude toward robotic surgery in a general surgical outpatient clinic in Singapore, Asia. J. Clin. Transl. Res. 2022; 8(3): 224–233. PubMed Abstract\n\nDavis FD: Perceived Usefulness, Perceived Ease of Use, and User Acceptance of Information Technology. MIS Q. 1989; 13(3): 319. Publisher Full Text\n\nDiez Roux AV: Conceptual Approaches to the Study of Health Disparities. Annu. Rev. Public Health. 2012; 33(1): 41–58. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFalk RF, Miller NB: A primer for soft modeling. University of Akron Press; 1992.\n\nHair JF, Black WC, Babin BJ, et al.: Multivariate Data Analysis.2010.\n\nHair JF Jr, Hult M, Ringle CM, et al.: Manual de Partial Least Squares Structural Equation Modeling (PLS-SEM) (Segunda Edición). OmniaScience; 2019. Publisher Full Text\n\nHall MA, Dugan E, Zheng B, et al.: Trust in Physicians and Medical Institutions: What Is It, Can It Be Measured, and Does It Matter? Milbank Q. 2001; 79(4): 613–639. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHenseler J, Hubona G, Ray PA: Using PLS path modeling in new technology research: updated guidelines. Ind. Manag. Data Syst. 2016; 116(1): 2–20. Publisher Full Text\n\nHorowitz MC, Kahn L: What influences attitudes about artificial intelligence adoption: Evidence from U.S. local officials. PLoS One. 2021; 16(10): e0257732. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIrani M, Prabakar C, Nematian S, et al.: Patient Perceptions of Open, Laparoscopic, and Robotic Gynecological Surgeries. Biomed. Res. Int. 2016; 2016: 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKao H-Y, Yang Y-C, Hung Y-H, et al.: When Does Da Vanci Robotic Surgical Systems Come Into Play? Front. Public Health. 2022; 10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKim MO, Coiera E, Magrabi F: Problems with health information technology and their effects on care delivery and patient outcomes: a systematic review. J. Am. Med. Inform. Assoc. 2017; 24(2): 246–250. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKrot K, Rudawska I: The Role of Trust in Doctor-Patient Relationship: Qualitative Evaluation of Online Feedback from Polish Patients. Econ. Soc. 2016; 9(3): 76–88. Publisher Full Text\n\nMcCray AT: Promoting Health Literacy. J. Am. Med. Inform. Assoc. 2004; 12(2): 152–163. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcDermott H, Choudhury N, Lewin-Runacres M, et al.: Gender differences in understanding and acceptance of robot-assisted surgery. J. Robot. Surg. 2020; 14(1): 227–232. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNorman CD, Skinner HA: eHEALS: The eHealth Literacy Scale. J. Med. Internet Res. 2006; 8(4): e27. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNayak S, Nayak VC, Sathvika S: DATA File. Dataset. figshare. 2023a. Publisher Full Text\n\nNayak S, Sathvika S, Nayak V: RAS Paper: Figures. figshare. Figure. 2023b. Publisher Full Text\n\nNayak S, Nayak VC, Kamath R, et al.: DATA File. [Dataset]. figshare. 2023c. Publisher Full Text\n\nNayak S, Nayak VC, Sathvika S: RAS_Questionnaire. figshare. [Dataset]. Journal contribution. 2024. Publisher Full Text\n\nParija P, Tiwari P, Sharma P, et al.: Determinants of online health information-seeking behavior: A cross-sectional survey among residents of an urban settlement in Delhi. J. Educ. Health Promot. 2020; 9(1): 344. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPetrocchi S, Iannello P, Lecciso F, et al.: Interpersonal trust in doctor-patient relation: Evidence from dyadic analysis and association with quality of dyadic communication. Soc. Sci. Med. 2019; 235: 112391. PubMed Abstract | Publisher Full Text\n\nPrasad A: Robotic Surgery in India. J. Young Med. Res. 2013; 1(1). Publisher Full Text\n\nPuja Turakhia M: Using Principles of Co-Production to Improve Patient Care and Enhance Value. AMA J. Ethics. 2017; 19(11): 1125–1131. PubMed Abstract | Publisher Full Text\n\nSarstedt M, Ringle CM, Hair JF: Partial Least Squares Structural Equation Modeling. Handbook of Market Research. Springer International Publishing; 2017; pp. 1–40. Publisher Full Text\n\nTejaswi M: Robotic surgeries gaining acceptance among patients, surgeons in India. The Hindu. 2021.\n\nvan der Vaart R , van Deursen AJ , Drossaert CH, et al.: Does the eHealth Literacy Scale (eHEALS) Measure What it Intends to Measure? Validation of a Dutch Version of the eHEALS in Two Adult Populations. J. Med. Internet Res. 2011; 13(4): e86. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVinzi VE, Chin WW, Henseler J, et al.: Handbook of Partial Least Squares. Vinzi VE, Chin WW, Henseler J, Wang H, editors. Berlin Heidelberg: Springer; 2010. Publisher Full Text\n\nWasko, Faraj: Why Should I Share? Examining Social Capital and Knowledge Contribution in Electronic Networks of Practice. MIS Q. 2005; 29(1): 35. Publisher Full Text\n\nXie L, Zhang S, Xin M, et al.: Electronic health literacy and health-related outcomes among older adults: A systematic review. Prev. Med. 2022; 157: 106997. PubMed Abstract | Publisher Full Text\n\nXu RH, Zhou L-M, Wong EL-Y, et al.: The Association Between Patients’ eHealth Literacy and Satisfaction With Shared Decision-making and Well-being: Multicenter Cross-sectional Study. J. Med. Internet Res. 2021; 23(9): e26721. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXue R, Liu R: Statistical analysis of da Vinci procedure volumes of 2021 in the Chinese Mainland. Int. Surg. 2022; 4: 18–22. Publisher Full Text\n\nYang T, Wu Y: A Study on the Influence of Patient Participation on Patient Trust-Based on Sample Survey in China. Front. Psychol. 2018; 9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYuan T, Li XD, Zhang M, et al.: Impact of the eHealth literacy, knowledge, and attitudes on COVID-19 prevention behavior among residents in the second year of the COVID-19 pandemic: A cross-sectional study in Anhui Province, China. Front. Public Health. 2022; 10. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "285902",
"date": "11 Jun 2024",
"name": "Nripesh Kumar Nrip",
"expertise": [
"Reviewer Expertise Multidisciplinary",
"Specially Information Technology in various domain of Human and Society like Agriculture",
"Health care",
"Education etc."
],
"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: Exploring the acceptance of robotic-assisted surgery among the Indian population: An empirical investigation Authors: Smitha Nayak, Vinod C. Nayak, Sathvika G. S. Abstract and Introduction: The abstract provides a concise summary of the study, highlighting the key findings and significance of the research. The introduction effectively sets the stage by discussing the integration of technology in healthcare and the specific advancements brought by robotic-assisted surgery (RAS). It frames the research within the context of the Technology Acceptance Model (TAM) and emphasizes the importance of understanding patient perceptions and eHealth literacy in the adoption of RAS. Comments:\nThe background information is comprehensive and well-researched. The rationale for the study is clearly articulated. The objectives are well-defined and relevant\n\nMethods: The methodology section is detailed, describing the cross-sectional research design and the use of a structured questionnaire to gather data from 280 respondents. The incorporation of TAM and eHealth literacy into the conceptual framework is well-explained.\nComments:\nThe sample size is appropriate for the study. The use of both hard copy and digital questionnaires is commendable for flexibility. The inclusion criteria and recruitment process are clearly described. The statistical tools and techniques used (IBM SPSS and SmartPLS) are appropriate for the analysis.\nResults: The results are presented with clarity, supported by tables and figures. The study successfully establishes the reliability and validity of the constructs. The findings on the impact of trust, perceived ease of use (PEoU), perceived usefulness (PU), and eHealth literacy on behavioral intention are well-documented. Comments:\nThe use of structural modeling to evaluate the hypotheses is appropriate and well-executed. The results are statistically significant and contribute to the understanding of factors influencing the acceptance of RAS. The mediation analysis adds depth to the findings.\nDiscussion: The discussion section effectively interprets the results, linking them back to the theoretical framework and previous research. The emphasis on the role of trust and eHealth literacy in shaping patient attitudes and behavioral intentions is insightful. Comments:\nThe discussion is thorough and provides practical implications for the healthcare industry. The recommendations for promoting RAS acceptance through enhanced communication and education are well-founded. The potential influence of digital literacy on the adoption of advanced medical technologies is well-articulated.\nConclusion: The conclusion succinctly summarizes the key findings and underscores the importance of trust and eHealth literacy in the acceptance of RAS. The study’s contributions to the literature and practical applications are clearly stated. Comments:\nThe conclusion is concise and effectively wraps up the study. The emphasis on the role of healthcare professionals in educating patients about RAS is a valuable insight.\nOverall Assessment: This study makes significant contributions to the understanding of factors influencing the acceptance of robotic-assisted surgery among the Indian population. The integration of TAM and eHealth literacy provides a robust framework for analyzing patient behavior. The findings are well-supported by rigorous data analysis and offer practical recommendations for healthcare practitioners and policymakers.\nMinor Suggestions:\nEnsure consistency in the use of abbreviations (e.g., PU, PEoU, RAS) throughout the manuscript.\nFinal Decision: Accept with minor revisions.\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": "11841",
"date": "27 Jun 2024",
"name": "smitha nayak",
"role": "Author Response",
"response": "Thank you for reviewing the article. Your suggestions have indeed added value to the manuscript. I will respond to the review comments and as per your suggestions, I will resubmit the article after incorporating the suggested changes. I will ensure uniformity is maintained. Regards, Prof. Smitha Nayak"
}
]
}
] | 1
|
https://f1000research.com/articles/13-544
|
https://f1000research.com/articles/13-490/v1
|
17 May 24
|
{
"type": "Software Tool Article",
"title": "Leveraging Quadratic Polynomials in Python for Advanced Data Analysis",
"authors": [
"Rostyslav Sipakov",
"Olena Voloshkina",
"Anastasiia Kovalova",
"Olena Voloshkina",
"Anastasiia Kovalova"
],
"abstract": "Objectives This study aims to provide a comprehensive overview of the role of quadratic polynomials in data modeling and analysis, particularly in representing the curvature of natural phenomena.\n\nMethods We begin with a fundamental explanation of quadratic polynomials and describe their general forms and theoretical significance. We then explored the application of these polynomials in regression analysis, detailing the process of fitting quadratic models to the data using Python libraries NumPy and Matplotlib. The methodology also included calculation of the coefficient of determination (R-squared) to evaluate the polynomial model fit. This study utilizes illustratively generated data to demonstrate the application of quadratic polynomials in Python for robust data analysis.\n\nResults Using practical examples accompanied by Python scripts, this study demonstrated the application of quadratic polynomials to analyze data patterns. These examples illustrate the utility of quadratic models in applied analytics.\n\nConclusions This study bridges the gap between theoretical mathematical concepts and practical data analysis, thereby enhancing the understanding and interpretation of the data patterns. Furthermore, its implementation in Python, released under MIT’s license, offers an accessible tool for public use.",
"keywords": [
"python",
"quadratic polynomials",
"analyzing data",
"polynomial model"
],
"content": "1. Introduction\n\nIn our exploration of the quadratic polynomials in Python for data analysis, we found significant contributions across various domains, exemplifying their utility and versatility. Gong and Zhang (2021) presented a compelling application for predicting Python usage trends, and demonstrated a robust model fit with practical implications for software analytics. Python provides an ideal environment for the rapid prototyping of data analytic tools and includes powerful tools for visualization, data sharing, and statistical analysis, such as Matplotlib, iPython, NumPy, and SciPy (Alexander et al., 2017).\n\nThis underscores the ability of quadratic polynomials to capture complex patterns beyond the realms of traditional linear models. In the context of quadratic polynomial regression, it is essential to note that quadratic polynomial step regression is an advanced tool capable of utilizing orthogonal experimental data to build a regression model, while avoiding instability in the regression coefficients owing to the multicollinearity of the variables (Wang et al., 2014). This highlights the potential of quadratic polynomials for handling complex data relationships and providing accurate regression models. Gong and Zhang (2021) developed a polynomial regression model to predict the Python usage trends. Their model, which demonstrated high accuracy with a training set score of 0.912862 and a test set score of 0.886600, highlighted the effectiveness of quadratic polynomials in forecasting software usage patterns (Gong and Zhang, 2021).\n\nAladesanmi et al. (2021) illustrated the adaptability of quadratic polynomials in material science was illustrated by Aladesanmi et al. (2021), who applied these models to understand the wear rate and hardness of nanocomposites. Aladesanmi et al. (2021) employed quadratic polynomial regression to analyze the relationship between material hardness and wear rate in Ti and TiB2 nanocomposites. Their findings, indicating a better fit for the quadratic model with an Adjusted R-squared value of 0.8883, underscores the utility of quadratic polynomials in material science research (Aladesanmi et al., 2021). In epidemiology, Yadav (2020) leveraged quadratic polynomial regression models to analyze the COVID-19 epidemic in India, demonstrating its effectiveness in epidemic forecasting. This example reflects the predictive power of mathematical models and their crucial role in public health planning and responses (Yadav, 2020). In the context of urban development and assessment of geotechnical conditions, the incorporation of Python for data analysis, particularly through quadratic polynomials, can significantly enhance the understanding and monitoring of complex ground conditions (Kaliukh et al., 2022).\n\nIn summary, Python, with its extensive libraries and capabilities for rapid prototyping, visualization, and scientific computation, provides a robust platform for leveraging quadratic polynomials in advanced data-analysis tasks.\n\n\n2. Methods\n\nIn this study, we focused on applying quadratic polynomials in Python for data analysis, highlighting the importance of these mathematical expressions in modeling and interpreting complex datasets using the following key concepts:\n\n– Quadratic polynomials: Defined by the general form ax2+bx+c, where (a),(b),(c), are coefficients. These polynomials are essential for capturing curvature in datasets indicative of various natural and human-made phenomena.\n\n– Python libraries: NumPy is open source and is available at https://numpy.org, were used for numerical computations, and Matplotlib also is open source and is available at https://matplotlib.org), was used to plot the data and polynomial curves, showing how these tools were integrated for data analysis.\n\n– Regression analysis: Explains how quadratic polynomials can be fitted to data points to model relationships within the data, emphasizing practical applications through Python coding examples.\n\n– Coefficient of determination (R-squared): Discuss the computation and interpretation of R-squared to measure how well the polynomial model fits the data.\n\nA quadratic polynomial is an algebraic equation of the second degree, which includes a term raised to a power of two (squared). The general form of a quadratic polynomial isy=ax2+bx+c, where (y) is the dependent variable; (x) is the independent variable; and (a),(b),(c) are the coefficients of the polynomial estimated by the regression model. The quadratic term (ax2) allows the model to capture the curvature in the data, which is indicative of acceleration increases or decreases that are common in many natural phenomena.\n\nSome key features of quadratic polynomials are that they have two terms with a variable (x) - one is (x) - squared, and the other is (x) to the first power. The (x2) term has a non-zero coefficient (a). This makes it a quadratic polynomial rather than a linear polynomial. When plotted, quadratic polynomials form a parabolic shape rather than a straight line. The quadratic polynomials have up to two distinct real roots for the equation x2+bx+c=0. These solutions were obtained by factoring or by using a quadratic formula. Examples of quadratic polynomials include the vertex form y=a(x−h)2+k, and the standard form y=ax2+bx+c. A quadratic polynomial has a squared, linear, and constant term, graphs as a parabola, and two roots at most.\n\nUnderstanding their structures allows many mathematical and real-world problems to be solved. We provide an example of the Python script below, which employs a quadratic polynomial fitting technique–a method used in regression analysis to model the relationship between a dependent variable and one or more independent variables. In this case, the independent variable is time (represented in months) and the dependent variable is the metric of interest (such as pollution levels and sales figures).\n\nAfter fitting the quadratic polynomial to the data, the script generated a smooth fitted curve that represented the estimated values of the dependent variable across a range of independent variables. This curve helps to visualize the overall trend and any potential seasonal patterns or anomalies in the dataset.\n\nThe coefficient of determination, commonly known as R-squared (R2), was then calculated to quantify the goodness of fit of the polynomial model. It is a statistical measure that indicates the proportion of variance in the dependent variable that is predictable from independent variable(s). An (R2) value of one (1) indicated a perfect fit, indicating that the model explained all the data variability around its mean. In contrast, an (R2) value closer to zero (0) indicates that the model fails to accurately model the data.\n\nFor more in-depth information on quadratic polynomial fitting and calculation of the coefficient of determination, the following sources (Norman R. Draper and Harry Smith, 2014; Douglas et al., 2021) provide a comprehensive overview of seminal works on regression analysis and detailed explanations of various regression techniques, including quadratic polynomial fitting and interpretation (R2).\n\nNext, we applied quadratic polynomial fitting and R-squared in Python for the data analysis. In this case, the Python script exemplifies the application of regression analysis using the NumPy and Matplotlib libraries to model and visualize trends in time-series data. A core component of this analysis is the fitting of a quadratic polynomial to the data, grounded in the principles of statistical learning.\n\nIn Python, this was achieved using the 'Polynomial.fit' method from the NumPy library, which computes the least-squares fit of a polynomial of specified degree to the given data. The snippet calculates the optimal values for coefficients (a),(b),(c) that minimize the sum of the squared differences between the observed values and values predicted by the polynomial, thereby effectively “fitting” the curve to the data, which Python-formatted version of code snippet similar to:\n\nWith the fitted polynomial, our script generates a curve across a continuum of points within the data range, which was visualized using Matplotlib’s plotting function and the Python-formatted version of the code snippet similar to:\n\nThe coefficient of determination, R2, was subsequently computed to assess the fit quality. Python was used to compare the variance of the residuals (the differences between the observed and predicted values) with the total variance of the data, and the corresponding code snippet is similar to:\n\nAn (R2) value close to one (1) suggests that the model explains a large portion of the variance in the response variable, indicating a strong fit. Conversely, a value near zero (0) suggests the model does not explain the variance well.\n\nThe following sources (VanderPlas, 2016; McKinney, 2017) provide a comprehensive overview of Python’s theoretical background and practical application. These resources offer a deep dive into data analysis using Python, including comprehensive guidance on regression analysis, and robust examples that bridge theory with practice.\n\nThis section details the implementation of quadratic polynomial models in Python that are used in various applications, as demonstrated in this study. The core of the implementation involved the use of Python NumPy and Matplotlib libraries for mathematical operations and visualizations. The polynomial model is defined by the equation ax2+bx+c, where (a),(b),(c), are the coefficients optimized to fit the data points collected in different studies. The fitting process utilizes the 'Polynomial.fit' method, which employs a least-squares polynomial fit. To ensure robustness and accuracy, the implementation also included calculation of the coefficient of determination (R2) using NumPy’s correlation function. This metric helps to assess the polynomial fit to the data, which is essential for the applications discussed, ranging from trend analysis in software usage to predicting the material properties of nanocomposites.\n\nIn the next step, we used Python to present an applied exploration of quadratic polynomial fitting and the coefficient of determination (R-squared) within the context of data analysis. The following Python script is a practical implementation tool for researchers and analysts: It begins by prompting the user to describe the dataset, such as a location or a specific environmental metric, such as the PM2.5 air pollution index. This interactivity ensures that the resulting visualization is tailored and informative. The Python-formatted version of the code snippet of this part of our script similar to:\n\nThe script reads data from a CSV file using Pandas, a library that excels in data manipulation. The data consists of monthly observations of the chosen metric. You can see this implementation in the Python-formatted version of the code snippet similar to:\n\nAs described above, with the data in hand, the NumPy library’s 'Polynomial.fit' function is employed to fit a quadratic polynomial to these observations. This is an essential step in modeling nonlinear behavior, accommodating potential fluctuations in data that a simple linear model would miss. Subsequently, the script computes the fitted values and leverages them to calculate the R-squared values. This statistic conveys the proportion of variance in the dependent variable explained by the independent variable. The Matplotlib library was then used to graphically represent the data along with the fitted curve, visually comparing the actual data points with those of the predictive model.\n\nAfter developing the script using the quadratic polynomial models described above, the complete Python code was hosted on GitHub (Sipakov, 2024), enabling replication and further exploration of the findings. To facilitate ease of use and accessibility, the code was made available through MyBinder.org (https://mybinder.org/v2/gh/rsipakov/QuadraticPolynomialsPyDA/main), allowing it to operate in a live environment without the need for local setup. This implementation ensures that other researchers can directly interact with the codebase, providing a dynamic way to validate and extend research findings.\n\nThe software tool based on quadratic polynomial models requires the following system setup and workflow: Operating System—Windows, macOS, or Linux; Python Version—Python 3.6 or later; dependencies —NumPy, Matplotlib (the latest versions are recommended), memory, at least 4GB of RAM; Processor, minimum 1GHz processor, or faster. The software is accessible through MyBinder.org, requires no local installation, and is fully configured to run in any web browser, ensuring its ease of use and reproducibility.\n\nTo begin the installation process, it is imperative to ensure that Python is installed in the operating system. If Python is not present, it can be acquired from Python’s official website python.org. After successful installation of Python, the next step involved installing the necessary libraries. This can be achieved through the Python Package Index (PyPI) using a PIP installer. Execute the following command in the command prompt or terminal to install the required libraries: 'pip install numpy matplotlib'. This command installs NumPy, which is essential for numerical computations, and Matplotlib, a library for plotting graphs and effectively visualizing the data.\n\n\n3. Results\n\nThe quadratic polynomial fitting method used in this study demonstrates Python's ability to effectively manage and analyze complex datasets. The datasets used herein are illustratively generated, serving as a basis for demonstrating the potential applications of quadratic polynomial models. The fitting process provided a smooth curve aligned closely with the observed data points, indicating robust model performance. Notably, the computed coefficient of determination, R-squared (R²), was substantially high, reflecting a strong correlation between the observed values and those predicted by the model. This statistical measure underpins the polynomial's ability to capture and explain variability in the data effectively, which is crucial for validating the regression model used in this analysis. Figure 1 illustrates the quadratic polynomial curve fitted to the observed data points using Python's plotting library Matplotlib.\n\nThe curve represents the model obtained from regression analysis, where the quadratic polynomial provides a significant fit to the data, as evidenced by the computed R-squared value. The axes were labeled to identify the independent variable (x-axis) and dependent variable (y-axis), and a legend was included to differentiate between the observed data points and fitted polynomial curve. The smoothness of the curve indicates the effectiveness of the model in capturing trends within the dataset, which can be utilized for predictive analytics and further statistical inferences. After configuring the plot with the necessary parameters for clear and informative visualization, it was generated using the 'plt. show()' function in Matplotlib.\n\n\n4. Discussion\n\nQuadratic polynomials are valued for their ability to model nonlinear relationships in various data contexts, balancing computational efficiency, and interpretability. However, their performance can be limited when confronted with complex multivariable systems in which more sophisticated statistical models may be more accurate. Future research could address these challenges by focusing on several advancements in quadratic polynomial modeling. Incorporating regularization techniques is recommended to counteract overfitting, particularly for datasets with intricate structures. Exploring hybrid models that merge the clear interpretive benefits of quadratic polynomials with the robust capabilities of machine learning algorithms could also enhance predictive accuracy.\n\nMoreover, the development of adaptive polynomial models that adjust their parameters based on real-time data inputs can significantly improve the dynamic data analysis. Extending these models to operate within multiscale frameworks may offer deeper insights into various levels of data structure, ensuring a comprehensive understanding of complex patterns. These enhancements are crucial for extending the utility of quadratic polynomials beyond their current capabilities and facilitating more accurate and efficient statistical analyses across diverse datasets.\n\nThis study acknowledges that the effectiveness of quadratic polynomials, like any statistical model, is contingent on the quality and volume of the data available. To mitigate potential biases and inaccuracies in the input data, the data collection methodology should include rigorous data preprocessing steps, such as outlier removal, normalization, and feature selection, which are crucial for enhancing the reliability of the research. Despite the potential of more advanced models, this study primarily advocates quadratic polynomials because of their suitability for datasets exhibiting quadratic relationships, which are frequently encountered in environment-related target research. However, future research should continue to explore the comparative dynamic performance of quadratic polynomials, for example, the performance of benchmarking against contemporary machine-learning algorithms to ensure a comprehensive understanding of their relative merits, possibly extending the use of hybrid approaches that combine the strengths of traditional polynomial models and cutting-edge machine-learning techniques.\n\nWhile quadratic models offer simplicity and clarity, they may only capture part of the complexity of data as effectively as some machine-learning models. However, their computational efficiency and suitability for smaller datasets can be advantageous for specific scenarios.\n\n\n5. Conclusion\n\nThese findings highlight the practical utility of the quadratic polynomials in Python for predictive analytics. The application of these polynomials in regression analysis, as demonstrated through Python scripts and methodologies, bridges theoretical concepts with real-world data analytics and enhances the interpretative power of statistical models in research. The high R-squared value obtained confirms the model's accuracy and predictive performance, making it a valuable tool for researchers and analysts seeking to conduct sophisticated data analyses. It is important to acknowledge, however, that the dataset used in this study were illustratively generated, which may limit the generalizability of the results to real-world datasets with more complex and unpredictable patterns. Furthermore, integrating Python libraries such as NumPy and Matplotlib in this process underscores the adaptability and efficiency of Python for handling complex and nuanced datasets across various research domains.\n\n\nEthical compliance\n\nAll procedures involving human participants were performed in accordance with the ethical standards of the Institutional and National Research Committee.\n\n\nAuthor contributions\n\nRostyslav Sipakov contributed to the research design, implementation, and manuscript writing. Dr. Voloshkina and Dr. Kovalova helped implement and analyze the results. All authors have seen and agreed to the final content of the manuscript.",
"appendix": "Data availability statement\n\nNo data is associated with this article.\n\n\nReferences\n\nAladesanmi VI, Fatoba OS, Jen TC, et al.: Python Data Analysis and Regression Plots of Wear and Hardness Characteristics of Laser Cladded Ti and TiB2 Nanocomposites on Steel Rail. 2021 IEEE 12th International Conference on Mechanical and Intelligent Manufacturing Technologies (ICMIMT). 2021; pp. 40–44. Publisher Full Text\n\nAlexander WM, Ficarro SB, Adelmant G, et al.: multiplierzv2.0: a python-based ecosystem for shared access and analysis of native mass spectrometry data. Proteomics. 2017; 17(15-16): 1700091. PubMed Abstract | Publisher Full Text\n\nDraper NR, Smith H: Applied Regression Analysis. 3rd ed.New York: John Wiley; 2014. 978-1-118-62568-2. Reference Source\n\nGong Y, Zhang P: Predictive Analysis and Research Of Python Usage Rate Based on Polynomial Regression Model. 2021 3rd International Conference on Artificial Intelligence and Advanced Manufacture (AIAM). 2021; pp. 266–270. Publisher Full Text\n\nKaliukh I, Voloshkina O, Efimenko V, et al.: Modern Technologies of Internet of Things in the Restrained Urban Development for Complicated Ground Conditions. 16th International Conference Monitoring of Geological Processes and Ecological Condition of the Environment. 2022; pp. 1–5. Publisher Full Text\n\nMcKinney W: Python for Data Analysis. 2nd ed.O'Reilly Media, Inc.; 2017. 9781491957660. Reference Source\n\nMontgomery DC, Peck EA, Geoffrey Vining G: Introduction to Linear Regression Analysis. 6th ed.New York: John Wiley; 2021. 978-1-119-57875-8. Reference Source\n\nSipakov R: rsipakov/QuadraticPolynomialsPyDA: Utilizing quadratic polynomials within Python to conduct sophisticated data analysis. (v0.0.1). Zenodo. 2024. Publisher Full Text\n\nVanderPlas J: Python Data Science Handbook. O'Reilly Media, Inc.; 2016. 9781491912058. Reference Source\n\nWang J, Sun A, Gao Q, et al.: Slag material's proportion optimised by polynomial regression. Proceedings of the Institution of Civil Engineers - Construction Materials. 2014; 167(1): 8–13. Publisher Full Text\n\nYadav RS: Data analysis of COVID-2019 epidemic using machine learning methods: a case study of India. Int. J. Inf. Technol. 2020; 12(4): 1321–1330. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "305465",
"date": "29 Jul 2024",
"name": "Selim Molla",
"expertise": [
"Reviewer Expertise Mathematical modeling",
"Discrete computer modeling and simulation",
"Machine learning",
"and Data analytics"
],
"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 is fundamentally sound and makes a significant contribution to the application of quadratic polynomials in data analysis using Python. However, to enhance clarity, completeness, and practical utility, the following revisions are recommended:\nIntroduction: Detailed Explanation of Suitability Improvement: Provide a more detailed explanation of why quadratic polynomials are particularly suitable for modelling and analysing data, compared to other polynomial or non-linear models. Details: Explain the unique advantages of quadratic polynomials in capturing curvature and non-linear relationships. Compare briefly with other models (e.g., linear, cubic polynomials) to highlight the specific scenarios where quadratic polynomials are most effective. Methods: Data Preprocessing Steps Improvement: Include a more detailed explanation of the data preprocessing steps, such as handling missing values or outliers. Details: Add a subsection detailing the preprocessing steps taken before fitting the quadratic model. This should include techniques for handling missing data, outlier detection and treatment, and any data normalization or scaling applied. Methods: Discussion of R-squared Limitations Improvement: Briefly discuss the limitations of using R-squared as the sole measure of model fit and suggest additional metrics. Details: Include a paragraph explaining that while R-squared is useful, it has limitations, especially in non-linear contexts. Suggest other metrics like Adjusted R-squared, Mean Squared Error (MSE), or Root Mean Squared Error (RMSE) to provide a more comprehensive evaluation. Results: Comparison with Other Models Improvement: Include a comparison with other models, such as linear regression or higher-degree polynomials, to provide a broader perspective on the performance of quadratic models. Details: Add a section that compares the performance of quadratic polynomials with linear and cubic models using the same datasets. Use metrics like R-squared, Adjusted R-squared, and MSE to compare the fit and predictive accuracy. Discussion: Challenges and Limitations Improvement: Delve deeper into the potential challenges and limitations of quadratic polynomials, such as overfitting or sensitivity to data variability. Details: Discuss scenarios where quadratic polynomials might overfit, particularly with small or noisy datasets. Provide suggestions for mitigating these issues, such as regularization techniques or cross-validation methods. Mention the sensitivity of quadratic models to data variability and how to handle such cases.\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": "12123",
"date": "20 Aug 2024",
"name": "Rostyslav Sipakov",
"role": "Author Response",
"response": "Dear Selim Molla, Thank you very much for your valuable comments. Based on your comments, we have revised and highlighted the article in red font. Due to the significant volume of changes we have made, including new figures, we provide a brief description of what we have done below. The full text of the preprint of revision 1 can be obtained via the following link: https://arxiv.org/abs/2402.06133. Please wait for the updated version (version 3) to be published. Announcement Schedule Thursday 20:00 (08/01/2024) Also, a new version has been submitted to the editorial office, and we hope it will be published soon. Within one business day, we will also publish the updated code on GitHub. What has been done: Point 1. Introduction: Detailed Explanation of Suitability. Response 1: This paper highlights quadratic polynomials' unique advantages in capturing curvature and non-linear relationships. It also includes a brief comparison with other models, such as linear and cubic polynomials, emphasizing specific scenarios where quadratic polynomials are most effective. Point 2: Methods: Data Preprocessing Steps Response 2: A new subsection has been added detailing the preprocessing steps undertaken before fitting the quadratic model. This includes techniques for handling missing data, detecting and treating outliers, and applying data normalization or scaling. This addition aims to provide a clearer understanding of the steps taken to prepare the data for analysis. Point 3: Methods: Discussion of R-squared Limitations Response 3: The methods section now contains a paragraph discussing the limitations of using R-squared as the sole measure of model fit. It suggests additional metrics such as Adjusted R-squared, Mean Squared Error (MSE), and Root Mean Squared Error (RMSE) to offer a more comprehensive evaluation of model performance. Point 4: Results: Comparison with Other Models Response 4: A new section has been included comparing the performance of quadratic polynomials with linear and cubic models using the same datasets. The comparison uses metrics like R-squared, Adjusted R-squared, and MSE to evaluate the fit and predictive accuracy, providing a broader perspective on the effectiveness of quadratic models. Point 5: Discussion: Challenges and Limitations Response 5: The discussion now delves deeper into the potential challenges and limitations of quadratic polynomials, such as overfitting and sensitivity to data variability. It addresses scenarios where quadratic polynomials might overfit, particularly with small or noisy datasets, and suggests methods for mitigating these issues, including regularization techniques and cross-validation methods. This addition aims to provide a more balanced view of the use of quadratic polynomials in data analysis."
},
{
"c_id": "12264",
"date": "23 Aug 2024",
"name": "Rostyslav Sipakov",
"role": "Author Response",
"response": "Dear Selim Molla, We have received a notification from the editorial board that version 2 of our manuscript has been publicly published. However, we are currently working on version 3 to address the comments provided by another reviewer. Nonetheless, we would greatly appreciate your feedback regarding your significant conceptual remarks, which we have endeavored to incorporate into version 2 of our manuscript. Once again, thank you very much for your attention and for providing valuable conceptual insights into our work. Sincerely, Dr. Sipakov"
}
]
},
{
"id": "290970",
"date": "08 Aug 2024",
"name": "Qiao Wang",
"expertise": [
"Reviewer Expertise Data analytics"
],
"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 explores modelling using quadratic polynomials in Python for data analysis applications. However, the study is limited to the single variable case, which does not meet the standards of current applications. In regression analysis, multivariate quadratic polynomial models or more generalized higher order polynomial regressions are typically used, but these crucial aspects are not covered in the current work. I have comments as below:\n1. The \"methods\" outlined in this article lack distinction, since it is a naive description on tool software; as a research article, they should be more prominently highlighted.\n2. The quadratic polynomial discussed in Section 2.1 mainly addresses the single-variable case. However, in a broader viewpoint, polynomial regression encompasses multivariable contexts, with its theoretical underpinnings and algorithms applied across various fields. I believe the explanation in this section could be revised and enhanced extensively.\n3. This entire subsection 2.1 could be reformulated using quadratic forms, along with pertinent linear algebra and matrix theory. Failing to do so would limit the model to a single-variable scenario.\n4. Section 3 solely demonstrates a standard example in the single-variable scenario. However, I recommend improving the clarity of its capabilities and limitations by introducing a counterexample, such as a dataset that fits well with a cubic curve but may fail when approximated with quadratic polynomial models.\nTo summarize, this article's discussion on the Python library for quadratic regression modeling is limited to single-variable scenarios and does not effectively showcase the model's fitting capabilities. In my opinion, the content is overly simplistic and does not adequately address practical data analysis applications. Therefore, a thorough major revision is necessary.\n\nIs the rationale for developing the new software tool clearly explained? No\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? Partly\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Partly",
"responses": [
{
"c_id": "12208",
"date": "13 Aug 2024",
"name": "Rostyslav Sipakov",
"role": "Author Response",
"response": "Dear Dr. Wang, Thank you very much for your review, which is of significant importance to our study. Although we aimed to present a simple and accessible tool for researchers with basic knowledge of Python programming, the comments from the previous reviewer regarding pre-processing and limitations and your comments regarding multivariate quadratic polynomial models will allow us to present a substantial version of this tool. For technical reasons, your comments were published after we submitted a new version (revision 1) of the manuscript to the editorial office based on the previous reviewer's comments. Nevertheless, we have begun work on a new version (revision 2) of the manuscript to reflect your valuable comments. Thank you once again for providing the opportunity to significantly improve our study. Sincerely, Dr. Sipakov"
}
]
}
] | 1
|
https://f1000research.com/articles/13-490
|
https://f1000research.com/articles/12-1536/v1
|
30 Nov 23
|
{
"type": "Research Article",
"title": "Time to sense biofield (Prana) experiences between hands: A preliminary single blinded randomised controlled trial",
"authors": [
"Vinu Vijayakumar",
"Srikanth Nagaraja Jois",
"Sumanth Mallikarjuna Majgi",
"Nagendra Prasad Krishnamurthy",
"Roopa Nanjunda swamy",
"Vinu Vijayakumar",
"Sumanth Mallikarjuna Majgi",
"Nagendra Prasad Krishnamurthy",
"Roopa Nanjunda swamy"
],
"abstract": "Aims: There is minimal research on the duration of biofield experiences. This preliminary study used the experiential learning practice of Master Choa Kok Sui’s hands sensitisation to determine the duration to experience biofield sensations in between hands and to find the relationship between learning style preferences and biofield sensations. Methods: This randomised controlled, single blinded trial included 88 male and female pre-service teachers, aged 22.8 ±1.2 years. Learning Style questionnaire, Ruler drop test, and Six Letter Cancellation tests were administered to participants and randomised into two groups. The experimental (hands facing each other as introduced by Master Choa Kok Sui) and sham (hands facing opposite) groups practiced hands sensitisation. A semi-structured questionnaire was provided to gather information about biofield sensations and the time it took to experience these sensations between the hands. Results: All (100%) of the participants in the experimental group (N=44) and 29.55% in the sham group (N=13) reported experiencing biofield sensations. A significant difference was found in, magnetic, temperature variation, and pain sensations between experimental and sham groups (X2= 59.20, p<.001). In the experimental group, the average time taken to first experience magnetic sensation, other biofield sensations and temperature variation was 34.84±12.97, 40.28± 20.96 and 42.50±19.79, respectively. Minimum time taken to first experience biofield sensation was 5 seconds and lasted up to study duration of 120 seconds. There was no correlation found between reaction time, attention, and the time needed to experience biofield sensations. Conclusions: The duration to experience the novel biofield sensation was described in this study.",
"keywords": [
"Cognition",
"complementary therapy",
"Pranic Healing",
"Yoga."
],
"content": "Introduction\n\nComplementary therapies are employed as a supplement to traditional healthcare systems around the world. They cover a various range of treatment methods, including biofield therapies. Healing touch, Pranic healing, Reiki, Qigong are examples of biofield therapies. According to the WHO Global Report on Traditional and Complementary Medicine, 12 member states have reported to use biofield therapies.1 Biofield is variously known as “prana,” “ki,” and “chi,” among other names around the world. Researchers were able to demonstrate the modulating effect of the immune response on mice through biofield therapy.2 Pranic Healing is suggested to promote subjective well-being by utilising ‘prana’ or vital energy.3\n\nBiofield sensations are the perception of subtle sensations without the presence of external stimuli. The sensations felt by the therapist during biofield therapy are helpful to measure and manage the client’s experience of biofield.4,5 Energy sensations of hands were reported during Meditation on Twin Hearts Practice.6 Hands sensitisation technique is used in pranic healing training.7,8\n\nThe process of learning through experience is known as experiential learning, and it involves the construction of knowledge from real-life situations. Experiences from the environment influence the sensory process and perception of stimuli while engaging in experience-based activity or learning.9 Based on the theory of experiential learning, learning styles have been represented by many theorists uniquely and combinations of factors have been expressed differently.10 According to Honey and Mumford’s11 model, learning styles consist of activist, reflector, theorist, and pragmatist. Activists are typically involved in and appreciate current experiences, reflectors are interested in analysing their experiences, theorists form conclusions based on their experiences, and pragmatists contemplate and take the next step.12 Any stage of learning can be entered at any time, and the preferred learning style is influenced by attention, concentration, personality types and environmental factors.13,14 Previously we have reported on the relationship between personality type and sensation between hands.15 The time taken to perceive (reaction time) initially the subtle sensations between hands were not studied. Literature regarding the same is scarce.\n\nIndividual differences in biofield sensations are related to self-awareness and sensitivity to others. Experiences with extrasensory perception and an individual’s capacity to be aware of biofield collectively contribute to shaping biofield sensations.16 Somatic sensations during biofield practice are connected to cognitive-perceptual and personality characteristics.17,18 Identification and recognition of sensations varies from person to person based on expectations, motivations and the factors that truly influence and control that environment.19 Reaction time influences the encoding of a natural activity through experiential learning. Learning by doing is much quicker in enacting a novel naturalistic activity compared to merely observing and then enacting the same activity performed by someone else.20\n\nReaction time has been found to be related to the chronometry of cognitive processing, it helps in examining models of information processing and to explore the differences in cognitive abilities.21 Chronometry is the science of measuring time. The time it takes for visual, auditory, and tactile sensations,22,23 and the duration of olfactory and spontaneous sensations has been demonstrated in previous studies.24 Focused attention to specific body parts are influential in detecting spontaneous sensations, the distribution of body fat and body mass index can impact sensory detection and pain sensitivity. For example, in comparison to individuals with a normal range body mass index, individuals with obesity have exhibited heightened sensitivity to pressure.23,25 Chronometry of biofield sensations have not yet been studied. The connection of focussed attention, reaction time and body mass on biofield sensations during sensitisation of hands practice is also unknown. Here this investigation aimed to find the time taken to first experience the biofield sensations between hands and the entire duration of sensations experienced during hand sensitization, as well as any possible connections between these sensations and variables including reaction time, sustained attention, and BMI. The study also investigates the connection between these practitioners’ predominant learning styles and qualitative expressions.\n\n\nMethods\n\nThe research was carried with the approval of the Independent Ethics Committee - World Pranic Healing Foundation, India (Ref: 2/2022/16/7/2022) on 20th July, 2022, and this trial has been registered at Clinical Trial Registry of India (CTRI/2022/08/044540) on 1st August, 2022. This study is reported inline with CONSORT guidelines.47\n\nThe study was conducted in August 2022, and it followed a randomised controlled participant blinded design. Participants of the study were relatively healthy pre-service teachers (students enrolled in Bachelor of Education) from Government College of Teacher Education (GCTE), Vasanth Mahal, Mysuru district. It is one of the teacher education centres in the Karnataka State under Department of State Educational Research and Training. Permission was obtained from Principal to conduct the experimental study among pre-service teachers. The sample size calculation was conducted in accordance with the guidelines set forth by Whitehead et al.,26 encompassing a 95% confidence interval, 80% power, and a standardized difference of 0.90,27 while also accounting for a 20% dropout rate, resulting in 42 participants per arm.\n\nThis study was conducted at the college auditorium Hall. All participants gathered in the hall received information about the study. An informational sheet detailing the study was provided to each participant. Additionally, the study procedures were verbally explained to the participants, and this explanation was recorded to ensure accuracy and consistency in the process. Male and female candidates between 18 and 24 (22.8 ± 1.2) years were enrolled as per the inclusion criteria: students aged 18 or older, who agreed to take part in the study, and had no prior experience with Master Choa Kok Sui (MCKS) hands sensitisation practice were included.\n\nParticipants with known diabetes, hyperesthesia, peripheral neuropathy and sensory impairments) were excluded from the study. During baseline assessments, a qualified nurse inquired about participants’ health and whether they met the criteria to participate in the study. Additionally, medication taken in the previous 24 hours was recorded.\n\nPre-service teachers who signed a consent form and expressed an interest in participating in the study were accommodated in the hall. The demographic information, learning preferences and performance test results were obtained. The participants were divided into two groups (1:1) using the fishbowl method, and the groups were assigned using the coin toss method. The study participants were blinded to their condition. To prevent interference, only one group at a time engaged in sensitization practice within the hall, while the other group spent their time in a separate hall located 200 meters away from the study hall. The entire process of data collection and procedure administration was concluded over a span of five hours.\n\nMaster Choa Kok Sui’s sensitization hand practise involved the steps as follows.7 Practise abdominal breathing while sitting comfortably with the spine straight. Connect the tongue to the palate, press the centre of the palms with the thumb, place hands parallel to one another at three inches, move your hands slightly back and forth, and be aware of the centres of palms and the tips of fingers. The whole trial of Sensitization practice was conducted three times with one minute break (approximately) between each session consisting of 120 seconds.\n\nThe sham group got identical instructions to the experimental group, with the exception of palm facing in opposite directions and height variation between hands of approximately 3 inches (Figure 1).\n\nDemographic details\n\nThe participants’ age, gender, locality, medications taken within the last 24 hours, and highest educational qualification were recorded. Height was measured using a measuring tape, and weight in kilograms was divided by height in meters squared to calculate the BMI (Body Mass Index) using the formula: BMI = weight (kg) /height2 (m2).\n\nSelf-administered questionnaires (Learning Style, Sensation of Hands timing Questionnaire) and performance tests (Six letter Cancellation Test, Ruler Drop Test) were used to measure different outcome variables.\n\nHoney and Mumford: Learning Styles Questionnaire: The Learning Styles Questionnaire (LSQ) is designed to measure learning preferences in individuals aged 16+, derived from the same conceptual basis as Kolb’s Learning Style Inventory. The Learning Style Questionnaire10 contains 80 statements representing four learning styles that may be predominant in an individual, the activist, the reflector, the theorist, and the pragmatist. Construct validity to Kolb’s learning styles was confirmed using factor analysis.28\n\nSix Letter Cancellation Test: A sheet of randomly printed letters of alphabet was provided with 6 target letters. Subjects can either select a single target letter at a time or all six letters at once, and can follow random, vertical, or horizontal paths on cancelling the letters. They can cancel maximum possible letters within 90 seconds of time.29\n\nReaction Time: To measure the Reaction time, Ruler Drop Test (RDT) was used Participants were asked to sit comfortably on a chair, ensuring that their dominant hand was positioned with the elbow bent at a 90-degree angle. The arm was then supported on the flat surface of the chair, with the open hand resting at the edge of the surface. A 60-cm-long ruler was dropped unexpectedly between the thumb and forefingers of their hand. They were instructed to quickly grasp the ruler as swiftly as possible. This ruler drop test (RDT) was repeated three times using the participant’s dominant hand. A rest interval of approximately 30 seconds was provided for each participant between each instance of dropping the ruler. The RT conversion was performed using the formula for a body in free fall under the influence of gravity (d= ½ gt2). The test score is the distance reached, with a lower distance indicating better performance.30\n\nThe sensation of Hands Timing Questionnaire (SHTQ): The Research Centre of the World Pranic Healing Foundation in India has created a new and self-administered questionnaire, which has undergone face validation. This questionnaire follows a semi-structured format and includes a combination of open-ended and closed-ended questions. These questions aim to capture information about participants’ experiences of sensations between their hands, the time it took to perceive these sensations, and how long the sensations persisted. Intensity of experiences among hands (left, right, both) and three open-ended questions on experience between hands were involved.\n\nThe open-ended questions included were 1) How did you feel about hand sensitisation practice? 2) In your opinion, what is the reason for experiencing these sensations between your hands 3) Describe the impact of the hand sensitisation experience on you?\n\nExperience of sensation of hands: To keep track of how long first experience took and how long they lasted, a stopwatch was displayed in a projector. The duration between hands that the biofield experienced throughout a 120-second period was self-reported. Experiments were repeated three times and average time has been considered. The pattern of experiences between the hands and which hand is more prominent in feeling the sensation were explored.\n\nThe experiences reported by participants in each group, along with the timings recorded in the Sensation Hands Timing Questionnaire, were thematically analysed using an inductive approach that aligned with the experiences during MCKS hands sensitisation.8 Microsoft Word was used. The meaningful words containing experiences between the hands were initially grouped by the first author. The inclusion of experiences similar to biofield sensations was then categorized by both the first and second authors. Additionally, other authors of this paper verified the data, and queries were addressed. Subject’s sensation between hands during three attempts was derived for how long it typically takes to have first experience and how long each experience lasts. The average value of sensations was calculated. Participants of time taken to first experience the sensations were categorised into no experience, 1-10 sec, 10.1-20 sec, 20.1-30 sec, 30.1 to 40 sec, and more than 40 sec. The duration of sensation experiences was categorised into no experience, 1-20 seconds, 20.1-40 sec, 40.1-60 sec, 60.1-80 sec, and more than 80 sec. The average time for each category of biofield sensations was also calculated.\n\nFurthermore, sensation experiences were classified as single, two sensations and three or more felt at same time. The association between the reported sensations and learning styles, as well as the association between the number of, biofield sensations and learning styles were analysed. Descriptive and inferential statistics using SPSS version 21 and Microsoft Excel were used to analyse the results.\n\n\nResults\n\nThe study comprised 88 students who were informed about the study and willingly took part by signing the consent form, with all participants meeting the eligibility criteria. Table 1 shows the demographic details and pre-assessment of pre-service teachers who participated in the trial.47 The experimental and sham groups each consisted of 44 participants. There were 65 women (72.7% in the experimental group and 75% in the sham group). 77.3% had a rural background and there was no significant difference found in participants’ gender (χ2 = 0.059, p = .808) or location (χ2 = 1.035, p = .309) between the experimental and sham groups. The experimental group’s body mass index (BMI) was 21.95 ± 6.38 and that of the Sham group was 20.41 ± 3.50. No significant difference was found between the experimental and sham groups in terms of BMI (χ2 = 4.286, p = .232). 14.77% of pre-service teachers had post-graduate degrees whereas the rest 85.23% had earned their degrees prior to enrolling in the pre-service teacher training programme. Importantly, the study did not experience any losses or exclusions following randomization, and no dropouts were recorded. Based on learning style theory, among all pre-service teachers, very high scores were identified in Active 49 (55.68%), Theorist 48 (54.55%), Pragmatist 38 (43.1%), and Reflector learning styles 27 (30.68%). Learning style preferences were categorized into very strong, strong, moderate, and low. No significant differences were found between the experimental and sham group pre-service teachers on active (2.295, p = .513), reflective (2.180, p = .703), theorist (1.307, p = .860), and pragmatic (3.197, p = .525) learning styles.\n\nPerformance tests involved the Six Letter Cancellation Test (SLCT) and Reaction Time (RT) Test. No significant differences were found between the experimental group (M = 53.03 ± 15.77) and the sham group (M = 47.29 ± 13.38) in SLCT (t = -1.837, p = .070) and RT (t = -0.104, p = .917). The mean reaction time of the experimental group and sham group were 0.21 ± 0.0 and 0.21 ± 0.03, respectively Right hand dominance was reported in all participants except one.\n\nAll the participants in the experimental group (N = 44) and 29.55% (N = 13) in the sham group reported experiencing biofield sensations. The experimental group reported magnetic sensations (81.81% (36/44) (“Magnetic pull between two palms,” “magnetic attraction“, “gravitational force”, and “Like a magnetic connection” etc), 50% (22/44) reported other bio-field sensations (“Felt hands are heavy”, “Something circling or spinning in mid of the palms”, “Felt like holding object”, “Something passing between hands”, “friction”, “vibration”, “lightness”, “heaviness”, “shaking”, “collision, pulsating” and “elastic force” etc), 9.1% (4/44) reported pain experiences (“Hand pain”, “shoulder pain” and “pain at the tip of tongue”) and 11.4% (5/44) of them reported temperature variation (“cold”, “heat” and “hotness”) (Figure 2).\n\nIn the sham group, 93.2% (41/44) reported pain experiences (“Hand pain”, “Left hand wrist pain”, “Little pain” and “Pain and attention”), 13.6% (6/44) reported other biofield sensation (“Felt a force like a thing between the hands”, “Hand pain with vibration”, “Weight lift feel”, “Hand pain and swimming feeling and Pulling” etc), 15.9% (7/44) reported magnetic sensations (“magnetic force”, “Pain and magnetic”) and 6.8% (3/44) of them reported awareness of temperature (“cold” and “pain with warmness”).\n\nIn terms of reporting magnetic sensations, pain, awareness of temperature, and other biofield sensation, there was a significant difference between the experimental and sham groups (χ2 = 59.20, p < .001).\n\nTable 2 shows there was no significant difference found between category of time taken to first experience the sensation between experimental and sham group participants.\n\nThe categorised experiences and mean time taken to first experience the sensations and extend of time the sensations were sustained (Duration) were identified. Figure 3 displays the radial plot on mean time to experience different biofield sensations, including the time taken to first experience various sensations and the experiences lasted. The average time it took to first experience biofield sensations of magnetic attraction, pulling sensation, some force, handshaking experience, temperature variation, heaviness, and vibration were 34.84, 34.07, 30, 36.50, 42.5, 48.5, and 54.33 seconds, respectively. The time it took to first experience sensations of hand shaking, lightness, pulse beating, collision, and elastic force were 37, 40, 58, 58, and 61 seconds, respectively. The minimum time taken to first experience the sensation and maximum time taken to end it. The shortest time it took to first experience a sensation was 5 seconds, and the duration of sensations lasted up to 120 seconds. The minimum time taken to experience magnetic, pulling, some force, hand shaking, Temperature variation, heaviness and vibration sensations were 5, 20, 18, 22.5, 14, 32 and 26.67 seconds, respectively.\n\nThe mean duration of each sensation was calculated, with magnetic, pulling, some force, hand shaking, awareness of temperature, heaviness, and vibration having mean durations of 43.39 sec, 43.67 sec, 73 sec, 59.83 sec, 61.70 sec, 52.00 sec, and 43 sec, respectively. The duration of lightness, pulse beating, collision, and elastic force were reported as single values of 80 sec, 40 sec, 62 sec, and 61 sec, respectively. Based on the thematic categorisation, mean time taken to first experience the magnetic sensation (34.84 ± 12.97) sec, other biofield sensations is (40.28 ± 20.96) sec and temperature variations were also noted (42.50 ± 19.79).\n\nParticipants’ reported sensations between their hands were divided into three categories: only one type of sensations, two types of sensations, and three or more sensations felt at same time. More people (N = 25, 56.82%) reported having only one sort of sensation than had two types (N = 18, 40.91%), three or more sensations (N = 1, 2.27%). Table 3 shows the association of learning styles and number of combinations of experiences from SHTQ. Participants of reflective (χ2 = 16.396, p = .012) and pragmatic (χ2 = 16.653, p = .034) learning style had a significant association with sensation experiences between hands. 34.09% of Strong reflective and 20.45% very high pragmatic learning preferred were reported more single experiences than others.\n\nFigure 4 shows the perceived intensity of sensation in hands. A significant difference was found between the experimental and sham groups in the perceived intensity of sensation in the hands (left, right, and both) (χ2 = 12.22, p < .001, N = 87). The intensity of experiences within the experimental group also were differed depending on whether they occurred in the left hand, right hand, or both hands (χ2 = 47.09, p < .001, N = 44). In the experimental group, 81.81% (36) reported the intensity of sensation experiences in both hands. 13.6% (6/44) of participants reported experiencing intensity at right hand, while only 4.54% (2/44) reported experiencing sensations in their left hand. In the sham group, 35.7% of participants experienced the intensity of the sensation in both hands, while 20.9% and 32.6% experienced the intensity in their left and right hands, respectively. However, within groups there was no significant difference.\n\nA significant negative correlation (r = -0.240, p = .025) exists between time taken to first experience sensation and duration of experiences among all participants. In the experimental group, the correlations of duration of experiences and time taken to first experience were negatively correlated (r = -0.326, p = .009,). No other correlations were found to be significant.\n\nIn open ended questions, participants expressed that the experiences were magical, good, and novel sensations were felt during the practice. Improvement in respiration, reduction of stress, calmness and improvement in mood and concentration were common among experimental group participants as shown in Table 4. Participants reported their opinion about the reason for experiencing biofield sensations and the impact of hands sensitisation practice. The reason for experiencing the sensations by participants reported attention and concentration, blood circulation, sense of calm, coordination of sensory organs in the body, etc. Self-reported and sparsely described feedback was noticed in sham group (Figure 5).\n\nAll participants gave consent for their picture to be used.\n\n\nDiscussion\n\nThis randomized controlled trial on sensitization between hands has demonstrated that both the experimental and sham groups self-reported an experience biofield sensations (prana) in between their hands. Furthermore, it has been determined that the interpretation of these sensations based on time is a viable approach. A survey of 18 people found that they perceived spontaneous sensations more in their hands than feet.31 In the current study, 57 participants experienced biofield sensation between their hands. The sham group participants experienced less (13) biofield sensations compared to experimental group (44). Majority of sham group participants reported hand, wrist, and arm pain during the experiment. It is possible that during the experience of pain, individuals may unconsciously direct their attention towards the affected area in the hands.32 This may be one of the reasons for not experiencing biofield sensations. The possibility of not experiencing sensations exists owing to the procedure of hand sensitising and sensitivity of hand. Hence the data on the chronometry and biofield energy experiences of the experimental group were analysed further based on duration. The time taken to first experience the sensations of magnetic, other biofield and temperature variation are 34.84, 40.28 and 42.50, respectively.\n\nPeople who frequently experience spontaneous sensations in their left hand, is due to the dominant right hemisphere activity of the brain.23 In this investigation, biofield sensations were experienced in both the hands of participants; they reported the intensity of experiences in both the hands. It is possible that both hemispheres are activated during MCKS hands sensitisation. People who followed MCKS Hands sensitisation procedure felt different biofield sensations in between hands. It positively affected the physical and psychological wellbeing.33 Biofield sensations have been reported following guidance or by following certain procedures mentioned in the biofield practices.34\n\nSomatic spontaneous sensations like tingling, temperature, beats, pulses, and pins have been previously investigated by detecting the spontaneous sensations within 10 seconds. Older participants reported more spontaneous sensations and duration of sensations when compared to youth population.35 Magnetic field, self-awareness, sensitivity to others and conscious intent are the factors influencing biofield awareness.16,36–39 So, the chances of variations in sensations are natural. MCKS sensitisation has been used as a learning practice to explore more about the subtle sensations or pranic energy sensations.7 According to the findings, different participants experienced biofield sensations for varying lengths of time during hand sensitization practice.\n\nBased on the context, environment, teaching method and subject of learning, the learning style preferences may get changed.40 There was no association found between sensation between hands and learning styles in this study, but the learning styles were associated to number of experiences. According to the attention processing model, participants are able to pay attention to a specific experience due to the difficulty of observing all other sensations at the same time.41 Self-analysis or introspection is the core to reflective learning. Complex Judgemental skills and problem-solving ability are the essential qualities of reflective thinkers.42 Recording the intricate interplay of various sensations over time can be challenging for self-interpretation. Consequently, participants might have opted to focus on individual biofield experiences throughout the entire practice session. For instance, sensations like “Magnetic with Cold or Warm” or “Pulling along with Other Sensations,” or experiencing three or more sensations simultaneously, could have posed difficulties in accurately reporting their timings. Similarly, individuals who lean toward pragmatic approaches tend to simplify matters by highlighting single experiences when drawing conclusions. Hence, participants with higher reflective and pragmatic tendencies displayed a tendency to articulate individual sensations rather than complex combinations as their reported experiences.\n\nThe negative correlation between the time taken to have the first experience and the overall duration of experiences in the experimental group suggests a complex relationship influenced by factors such as learning, adaptation, and familiarity.The time taken to experience biofield sensation were unrelated to reaction time, sustained attention, or body mass index. One study discovered that, paying attention to the hands improves the duration of experiences.35 Separating the conscious and unconscious sensory processes and connecting with attention is a difficult task.43 Mind wandering awareness has been linked to perception of spontaneous stimulus.44 One study revealed that the intensity of experience influences body mass index.45 Participants can have a better understanding of biofield experiences by receiving further training and learning about biofield-related therapy.46 In this study, hands-sensitization practise in the experimental group had a favourable effect on the participants, and the qualitative feedback supported the idea that biofield sensations improve current moods or states.33\n\nThis procedure’s replicability offers potential for future biofield research, with follow-up studies involving diverse participant groups to validate observed results’ consistency on time taken to experience biofield sensations.\n\nThe study’s questionnaire is unstandardized, necessitating the need to develop an instrument to measure time-related sensations between hands. Participants aged 18-24 were included, excluding older populations.\n\nThis study findings may inspire biofield researchers to conduct time-based cognition and perception experiments. Based on MCKS hand sensitization, a theory on biofield sensations might be constructed, which could then be utilised as a tool or technique for studying numerous subtle sensations.\n\nFurther research on the duration of biofield sensations using chronometry is needed. Research is needed on specific biofield sensation-based approaches, as neuropsychological evidence on palm sensations is limited. It’s unclear if cortical brain activation is related to pranic energy experiences. Both spontaneous sensations and MCKS Hands Sensitisation experiences start without stimulus, but differ in methods. Investigation is needed to understand similarities and differences.\n\n\nConclusion\n\nThis research emphasises the significance of recognising biofield sensations in hands sensitization practises. The MCKS hands sensitization practise research looked at biofield sensations between the hands under controlled settings. It kept track of time-related evaluations. It took 34.84, 54.33 and 42.5 seconds on average to initially feel magnetic attraction, vibration and temperature variation between hands. In the experimental group, there was a negative correlation between the time for the first experience and the overall duration of the experiences.",
"appendix": "Data availability\n\nFigshare: Time to experience Biofield Sensations Between Hands – A Randomised Control Trial, https://doi.org/10.6084/m9.figshare.24024948.v1. 47\n\nThis project contains the following underlying data:\n\n- Consent and Demographic Details.pdf\n\n- Master Sheet_ Pre service Teachers.xlsx\n\nFigshare: CONSORT checklist for ‘Time to sense biofield (Prana) experiences between hands: A preliminary single blinded randomised controlled trial’, https://doi.org/10.6084/m9.figshare.24024948.v1. 47\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 acknowledge Master Choa Kok Sui for teachings, guidance, blessings and board members of the World Pranic Healing Foundation, India, for encouragement, support, and funding. We thank the principal, Mrs Geethamba, along with staff of the Government College of Teacher Education, Vasanth Mahal Mysore, and the volunteers who participated in the study, as well as all members of our research centre for their valuable contributions.\n\n\nReferences\n\nWorld Health Organization: WHO global report on traditional and complementary medicine 2019. World Health Organization; 2019.\n\nGronowicz G, Secor ER Jr, Flynn JR, et al.: Human biofield therapy does not affect tumor size but modulates immune responses in a mouse model for breast cancer. J. Integr. Med. September 2016; 14(5): 389–399. PubMed Abstract | Publisher Full Text\n\nRajagopal R, Jois SN, Mallikarjuna Majgi S, et al.: Amelioration of mild and moderate depression through Pranic Healing as adjuvant therapy: randomised double-blind controlled trial. Australas. Psychiatry. August 2018; 26(1): 82–87. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDyer NL, Ali A, Baldwin AL, et al.: An Evaluation of the Subjective Experience of Receiving Reiki: Qualitative Results from a Pragmatic Effectiveness Study. J. Integr. Complement. Med. May 2022; 28(9): 739–748. PubMed Abstract | Publisher Full Text\n\nRowold J: Validity of the biofield assessment form (BAF). Eur. J. Integr. Med. August 2016; 8(4): 446–452. Publisher Full Text\n\nMeena BM, Manasa B, Vijayakumar V, et al.: Nursing Student’s Experiences of Meditation on Twin Hearts During Eight Weeks Practice: A Qualitative Content Analysis. SAGE Open Nurs. December 2021; 7: 237796082110521–237796082110510. PubMed Abstract | Publisher Full Text\n\nSui CK: The ancient science and art of pranic healing. Manila: PH: Institute for Inner Studies Publishing Foundation. Inc; 2015.\n\nBelal M, Mallikarjunappa MB, Nagaraj S, et al.: Understanding Pranic Energy Experiences: A Qualitative Approach. Adv. Mind Body Med. 2023; 37(1): 22–27. PubMed Abstract\n\nYeo RK, Marquardt MJ: (Re) interpreting action, learning, and experience: Integrating action learning and experiential learning for HRD. Hum. Resour.Dev.Q. March 2015; 26(1): 81–107. Publisher Full Text\n\nChilds-Kean L, Edwards M, Smith MD: Use of Learning Style Frameworks in Health Science Education. Am. J. Pharm. Educ. July 2020; 84(7): ajpe7885. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHoney P, Mumford A: 1992; The Manual of Learning Styles. 3rd ed.Maidenhead, Berkshire, UK: Honey Press.\n\nBenmarrakchi F, El Kafi J, Elhore A, et al.: Exploring the use of the ICT in supporting dyslexic students’ preferred learning styles: A preliminary evaluation. Educ. Inf. Technol. October 2016; 22: 2939–2957. Publisher Full Text\n\nNi D, Wang S, Liu G: The EEG-Based Attention Analysis in Multimedia m-Learning. Comput. Math. Methods Med. June 2020; 2020: 4837291–4837210. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSharp A: Jungian Learning Styles. Encyclopedia of the Sciences of Learning. Springer US; 2012; pp. 1672–1675. Publisher Full Text\n\nJois SN, Vinu V, Hiremath S, et al.: Personality Types and Prānic Energy Perceptions: An Exploratory Study. Siritual. Stud. November 2020; 6(2): 48–59. Reference Source\n\nNelson LA, Schwartz GE: Human biofield and intention detection: individual differences. J. Altern. Complement. Med. February 2005; 11(1): 93–101. PubMed Abstract | Publisher Full Text\n\nParra A, Giudici R: Cognitive-Perceptual Features Associated With Nonconventional Healing Practices. Imagin. Cogn. Pers. March 2020; 40(2): 126–142. Publisher Full Text\n\nTihanyi BT, Ferentzi E, Beissner F, et al.: The neuropsychophysiology of tingling. Conscious. Cogn. February 2018; 58: 97–110. PubMed Abstract | Publisher Full Text\n\nFeldman J: Information-theoretic signal detection theory. Psychol. Rev. 128(5): 976–987. von Stülpnagel R, Schult JC, Richter C, Steffens MC. Cognitive costs of encoding novel natural activities: Can “learning by doing” be distracting and deceptive? Q J Exp. Psychol. (Hove), 69(8):1545-63, August 2016. doi: 10.1080/17470218.2015.1087581. PMID: 26325343. Publisher Full Text\n\nBazilinskyy P, Winter J: Crowdsourced Measurement of Reaction Times to Audiovisual Stimuli With Various Degrees of Asynchrony. Hum. Factors. December 2018; 60(8): 1192–1206. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKranzler JH: Mental Chronometry.Seel NM, editor. Encyclopedia of the Sciences of Learning. Boston, MA: Springer; 2012. Publisher Full Text\n\nMc Govern EM, Butler JS, Beiser I, et al.: A comparison of stimulus presentation methods in temporal discrimination testing. Physiol. Meas. February 2017; 38(2): N57–N64. PubMed Abstract | Publisher Full Text\n\nMichael GA, Naveteur J: The tickly homunculus and the origins of spontaneous sensations arising on the hands. Conscious. Cogn. September 2011; 20(3): 603–617. PubMed Abstract | Publisher Full Text\n\nMillot JL, Laurent L, Casini L: The Influence of Odors on Time Perception. Front. Psychol. February 2016; 7(7): 181. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTashani OA, Astita R, Sharp D, et al.: Body mass index and distribution of body fat can influence sensory detection and pain sensitivity. Eur. J. Pain. August 2017; 21(7): 1186–1196. PubMed Abstract | Publisher Full Text\n\nWhitehead AL, Julious SA, Cooper CL, et al.: Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat. Methods Med. Res. June 2016; 25(3): 1057–1073. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJois SN, Manasa B, D’Souza L, et al.: Sensation of pranic energy between hands: an exploratory study. Indian J Anc Med Yoga. December 2017; 10(1): 5–1. Publisher Full Text Reference Source\n\nCockerton T, Naz R, Sheppard S: Factorial validity and internal reliability of Honey and Mumford’s Learning Styles Questionnaire. Psychol. Rep. October 2002; 91(2): 503–519. PubMed Abstract | Publisher Full Text\n\nPradhan B: Effect of kapalabhati on performance of six-letter cancellation and digit letter substitution task in adults. Int. J. Yoga. July 2013; 6(2): 128–130. PubMed Abstract | Publisher Full Text | Free Full Text\n\nÁngel Latorre-Roman P, Robles-Fuentes A, García-Pinillos F, et al.: Reaction Times of Preschool Children on the Ruler Drop Test: A Cross-Sectional Study with Reference Values. Percept. Mot. Skills. October 2018; 125(5): 866–878. PubMed Abstract | Publisher Full Text\n\nEfstathiou M, Delicato LS, Sedda A: Normal or tingly? A story about hands and feet. Somatosens. Mot. Res. March 2022; 39(1): 46–54. PubMed Abstract | Publisher Full Text\n\nLegrain V, Perchet C, García-Larrea L: Involuntary orienting of attention to nociceptive events: neural and behavioral signatures. J. Neurophysiol. October 2009; 102(4): 2423–2434. PubMed Abstract | Publisher Full Text\n\nJois SN, Aithal R, D’Souza L, et al.: The perception of prana and its effect on psychological well being. J. Res.: Bede Athenaeum. January 2015; 6(1): 210–215. Publisher Full Text\n\nNelson LA, Schwartz GE: Human biofield and intention detection: Individual differences. J. Altern. Complement. Med. February 2005; 11(1): 93–101. PubMed Abstract | Publisher Full Text\n\nNaveteur J, Dupuy MA, Gabrielli F, et al.: How we perceive our own hands: Effects of attention, aging, and sex. Somatosens. Mot. Res. September 2015; 32(4): 227–235. PubMed Abstract | Publisher Full Text\n\nJain S, Hammerschlag R, Mills P, et al.: Clinical Studies of Biofield Therapies: Summary, Methodological Challenges, and Recommendations. Glob. Adv. Health Med. November 2015; 4(Suppl): gahmj.2015.034–gahmj.2015.066. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTian LX, Pan YX, Metzner W, et al.: Bats respond to very weak magnetic fields. PLoS One. April 2015; 10(4). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMatos LC, Machado JP, Monteiro FJ, et al.: Perspectives, Measurability and Effects of Non-Contact Biofield-Based Practices: A Narrative Review of Quantitative Research. Int. J. Environ. Res. Public Health. June 2021; 18(12): 6397. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeck S, Corse G, Lu DF: Case Report: Energy Field Changes Approaching and During the Death Experience. Integr. Med (Encinitas). December 2016; 16(6): 36–42. PubMed Abstract\n\nPritchard A: Ways of learning: Learning theories for the classroom. Routledge; 2017.\n\nDriver J: A selective review of selective attention research from the past century. Br. J. Psychol. 2001 Feb; 92(Pt 1): 53–78. PubMed Abstract | Publisher Full Text\n\nGayathri B, Vedavyas R, Sharanya P, et al.: Effectiveness of reflective learning in skill-based teaching among postgraduate anesthesia students: An outcome-based study using video annotation tool. Med. J. Armed Forces India. February 2021; 77(Suppl 1): S202–S207. PubMed Abstract | Publisher Full Text | Free Full Text\n\nvan Boxtel JJ , Tsuchiya N, Koch C: Consciousness, and attention: on sufficiency and necessity. Front. Psychol. December 2010; 1: 217. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMichael GA, Tapiero I, Gálvez-García G, et al.: Thoughts and sensations, twin galaxies of the inner space: The propensity to mind-wander relates to spontaneous sensations arising on the hands. Conscious. Cogn. October 2017; 55: 223–231. PubMed Abstract | Publisher Full Text\n\nMichael GA, Naveteur J: The tickly homunculus and the origins of spontaneous sensations arising on the hands. Conscious. Cogn. 2011 Sep; 20(3): 603–617. PubMed Abstract | Publisher Full Text\n\nMiles P, True G: Reiki-review of a biofield therapy: history, theory, practice, and research. Altern. Ther. Health Med. March 2003; 9(2): 62–72. PubMed Abstract\n\nJois S, Vijayakumar V, Majgi SM, et al.: Time to experience Biofield Sensations Between Hands - A Randomised Control Trial. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "265638",
"date": "15 May 2024",
"name": "Ann Linda Baldwin",
"expertise": [
"Reviewer Expertise Physiology of mind-body interactions"
],
"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 Statements This study addresses an interesting topic, exploration of sensing the biofield between the hands, focusing on the time taken to sense the field. The number of participants included is statistically robust, and they are randomly assigned to an experimental or control group. The protocol is well described and most of the measurement tools are tested and well established. The analytical procedure appears to be adequate. However, there are problems with lack of clarity in the presentation of results and with the interpretation of observed differences in the results between the experimental and control groups.\nMajor Criticisms Abstract\nThe terms “Ruler Drop Test and Six Letter Cancellation Test are used without explanation of what they measure. It is stated that there is a significant difference in sensations of temperature variation between the groups, but this is not consistent with Figure 2. Units of time (seconds?) are missing There is no proper conclusion. Saying that something “was described” is not a conclusion.\nMethods Measurements. The Six Letter Cancellation Test is badly described and there is no explanation of what it is supposed to measure.\nResults\nA main result is that a much larger percentage of the control group experienced pain than the experimental group. To this reviewer, the obvious reason for this difference is that holding ones palms facing away from each other is much more difficult and uncomfortable than holding ones palms facing each other, and so could cause pain but this possibility is not even mentioned. Figure 2 only shows one generalized statistic comparing experimental and control groups. Please supply statistics for each of the different types of sensations. Are the data from Figure 3 and Table 3 from ALL participants or just the experimental group? Table 3 is difficult to understand. There are too many comparisons. What parameters are the listed p-values comparing?\nDiscussion In paragraph one, discuss reasons for why the experimental group participants felt more pain than the control group (such as the reason suggested by this reviewer). What is the point of comparing sensations in palms facing versus palms directed away? This was never explained. Maybe a more interesting comparison could be both groups with palms facing but only one performing abdominal breathing\nMinor Criticisms Results: Define SHTQ\nComments to Editor Although this study has many strengths, the major flaws concerning data presentation and interpretation need to be addressed.\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?\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": []
}
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https://f1000research.com/articles/12-1536
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https://f1000research.com/articles/13-83/v1
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24 Jan 24
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{
"type": "Study Protocol",
"title": "Evaluation of comparative efficacy of Tinospora cardifolia and Ricinus communis via nasal administration in the management of cervical spondylosis: a randomized controlled trial protocol",
"authors": [
"Madhvi Jain",
"Vinod Ade",
"Shweta Parwe",
"Punam Sawarkar",
"Madhvi Jain",
"Vinod Ade",
"Punam Sawarkar"
],
"abstract": "Background- Cervical spondylosis is a disease that is caused by the vitiation of only one bodily humor (dosha) (Vataja nanatmaja). The vata bodily humor (dosa) becomes vitiated and settles in the cervical (manya), creating neck pain and stiffness, which ultimately led to cervical spondylosis. Cervical spondylosis can be examined primarily under the generalization of cervical spondylosis because both conditions have many of the same symptoms. A disorder known as cervical spondylosis, which affects the cervical vertebra, is a degenerative condition of the cervical spine. In addition to having negative effects on a person's health, the disease also significantly lowers the quality of life and daily activities. Ayurveda suggested a treatment for cervical spondylosis to avoid and control the condition. There are numerous therapies in Ayurveda, and Oil administration through the nostrils has been given a significant role in upper clavicular disease (Uurdhvajatrugata roga). Oil administration through nostril therapy has been specifically recommended by Acharya Charka for the treatment of cervical spondylosis. The purpose of certain ayurvedic approaches in the management of cervical spondylosis. Methods: - 60 patients will be split into two groups for this investigation. A tinospora cardifolia and a group of drugs (Mashadi oil) will be given to the group through the nostrils for seven days at a dose of eight drops. The same will be used for the other 30 patients, i.e., group B with Ricinus Communis and a group of drugs (Erandadi oil) administered through the nostrils. Expected result: The result will be assessed on the baseline of objective parameters, and data will be compared after the treatment.",
"keywords": [
"Keywords – Cervical spondylosis",
"Oil administration through nostrils",
"Mashadi tail Oil administration through nostrils Erandadi tail Oil administration through nostrils."
],
"content": "Introduction\n\nAccording to Acharya Charak,1 80 diseases are caused by the vitiation of only one bodily humor (dosa) (vataj nanatamaj) in Ayurveda. The cervical (Manya) is the locomotor portion. Cervical spondylosis (Manayahstambh) is caused by excessive driving, excessive travel, daytime sleep, and prolonged sitting and standing (in a fixed posture). In addition, the air (vayu) is covered by the kapha of the cervical vein (Manyagata Siras), which results in stiffness and pain in the neck, which in turn causes cervical spondylosis.2 Pain and stiffness and restricted movements in human life are the two primary symptoms of cervical spondylosis.\n\nIn the current medical system, muscle relaxants, NSAIDs, analgesics, and corticosteroids are offered as the first line of treatment. The patient doesn't experience lasting relief, and long-term usage of these medications might have dangerous negative effects on patients.3\n\nCervical spondylosis is a common site for age-related neck spinal disk wear and strain. as a disk wears and compresses. When symptoms do show up, they include neck discomfort and stiffness. Sometimes, cervical spondylosis causes the space required by the spinal cord and the nerve root that passes through the spine to the rest of your body to shrink may encounter if the spinal cord or nerve roots are squeezed. Your arm, hand, legs, or feet may feel tingly, numb, or weak.4\n\nDegenerative changes are visible in 25% of persons under the age of 40, 50% of people over the age of 40, and 85% of people over the age of 60. The levels that are most frequently impacted are C6-C7 and C5-C6. The prevalence of neck discomfort in the general population varies from 0.4% to 41.5% at the point, from 4.8% to 79.5% over a year, and from 0.4% to 86.8% during a lifetime. According to the Global Burden of Disease 2015 study, low back, and neck pain continue to be the leading cause of years spent with a handicap.5\n\nOil administrate through the nostrils must be used as the initial kind of treatment in this situation. The upper neck areas are treated with Oil administration through the nostrils.6\n\nDue to its progressive character, cervical spondylosis disease has grown into a serious hazard to the working population. While modern medicine offers a variety of medical and surgical treatments, it is evident that none of them are effective for cervical spondylosis. According to established science, all forms of treatment only temporarily relieve symptoms. As a result, Ayurveda is increasingly being considered for chronic diseases.8\n\nCervical spondylosis is a condition that is becoming more common today due to the use of computers, excessive cell phone use, and heavy weightlifting by the younger generation. This affects the cervical region and arm and results in symptoms like pain, stiffness, headaches, restricted movement, and loss of motor function in the arm because of increased Vata bodily humor (dosa), which is located in the cervical region.9 As a result, acharyas have mentioned vata kapha decrease (Vatakapha sama) Sneha drugs should be used in Oil administration through nostrils, and dry steam (Ruksha Sweda).10\n\nमन्यास्तम्भेऽप्येतदेव विधानं, विशेषतो वातश्लेष्महरैर्नस्यै रूक्षस्वेदैश्चोपचरेत्||Su.chi.5/20\n\nAs stated by Acharya in “Nasa Hi Shiraso Dwaram,” enabling Oil administration through the nostrils Drug to enter the nasal route leads to Shringataka Marma and acts as the nursing the tissue (Dhatuposhana) and disease-free (Vyadhiharan) of the eye, ear, throat, etc.11 Mashadi tail has shown to be effective in preventing Manyahstambh (cervical spondylosis), but it consumes more than Erandadi tail because it contains 12 medications compared to just seven. Ksheerpaka Vidhi prepares erandadi tail with milk (ksheer), which has a soft (Mridu) effect, is nutritious for the nervous system, and is enriched with calcium.12 To compare the effectiveness of Eranda tail and Mashadi tail oil administration through nostrils in patients with cervical spondylosis, this study was conducted.\n\nEvaluation of the comparative efficacy of tinospora cardifolio and a group of drugs (Mashadi tail Oil administration through nostrils) administered through nostrils and Ricinus Communis and a group of drugs (Erandadi Taila Oil administration through nostrils) in the management of Manyasthambha (Cervical Spondylosis).\n\n\n\n1. To evaluate the efficacy of Mashadi taila oil administration through nostrils over a range of motion in the management of cervical spondylosis.\n\n2. To evaluate the efficacy of erandadi taila oil administration through nostrils over range of motion in the management of cervical spondylosis.\n\n3. To compare the efficacy of mashadi taila oil administration through nostrils and erandadi taila oil administration through nostrils over the range of motion in the management of cervical spondylosis.\n\n4. To evaluate the efficacy of mashadi taila oil administration through nostrils over pain (visual analog scale) in the management of cervical spondylosis.\n\n5. To evaluate the efficacy of erandadi taila oil administration through nostrils over pain (visual analog scale) in the management of cervical spondylosis.\n\n6. To compare the efficacy of mashadi taila oil administration through nostrils and erandadi taila oil administration through nostrils over pain (visual analog scale) in the management of cervical spondylosis.\n\n7. To evaluate the efficacy of Mashadi taila oil administration through nostrils over neck Disability Index in the management of cervical spondylosis.\n\n8. To evaluate the efficacy of erandadi taila oil administration through nostrils over the neck disability index in the management of cervical spondylosis.\n\n9. To compare the efficacy of mashadi tail oil administration through nostrils and erandadi tail oil administration through nostrils over the neck disability index in the management of cervical spondylosis.\n\n\nProtocol\n\nThe patients would be chosen from specialized periphery camps as well as the Mahatma Gandhi Ayurved College, Hospital & Research Center, Salad (H)'s Panchakarma OPD, and IPD. For the trial, a total of 60 participants gets enrolled. They will be divided into two teams. Group A uses Mashadi oil in the nostrils, while Group B uses Erandadi oil in the same way. At the beginning of the trial, all baseline parameters will be recorded. Both groups of patients will receive Oil administration through nostril treatment for seven days (Figure 1).\n\nRoles and responsibilities of committees: The study will start after clearance from the I.E.C. of Mahatma Gandhi Ayurveda College Hospital and Research Center, Salod (H.), Wardha. And after CTRI registration. Ref. No. CTRI/2023/03/050923. The committee will decide on the endpoint and oversee the trial as it progresses. The researcher will assess any adverse event and will be reported to the Ethics committee.\n\nGuidelines – SPIRIT Guidelines are being used for the study.\n\nA cervical spondylosis patient who has been diagnosed with patients who have impaired neck ROM. Patients of either gender who fall between the age range of 21 to 60 years (Right Lateral: 200, Left Lateral: 200, Flexion: 800, Extension: 700, Left Rotation: 900, Right Rotation: 900) are included in this study.\n\nSampling procedure- simple randomization. The researcher will enrol the participants, create the allocation sequence, and allocate them to the intervention.\n\nType of study – Interventional study\n\nStudy design – Randomized standard controlled double-blind superiority clinical trial.\n\nThe allocated intervention will blind participants.\n\n\n\n• Patient willing to give written informed consent.\n\n• Patients with either gender and within the age range of 21 to 60.13\n\n• Patients already diagnosed with cervical spondylosis, radiologically diagnosed with X-ray.\n\n• Patients who have less range of motion in the neck. (Right Lateral: 200; Left Lateral: 200; Flexion: 800; Extension: 700; Left Rotation: 900; Right Rotation: 900)\n\n• Suitable patients for oil administration through nostrils (Figure 2).14\n\n\n\n• Post-operated cases of cervical spondylosis.\n\n• Patients contraindicated for oil administration through nostrils.15\n\n• Traumatic cervical spine.\n\n• Congenital spine deformity.\n\n• Fracture of the cervical spine.\n\n➢ Study design-\n\nFigure 3 shows preperation of Ricinus commmunis oil.\n\nCharacteristics of drugs.\n\nOil administration through nostrilskarma Procedure16 -\n\n➢ Pre procedure (Poorvakarma)\n\nInstruments (Sambar Sangraha): For Oil administration through nostrils, pick a space with sufficient lighting and no airborne contaminants like smoke or dust. Collect the required supplies for Oil administration through the nostrils, including a table or a chair, supplies for steam, medicine, a towel, cotton, a serving bowl, and oil.\n\nPatient fit for the procedure (Aturasiddhata): To get oil administration through the nostrils, the patient's posture should allow him to lean comfortably returning to the backrest with his slightly arched neck. The patient should be forced to lie down on the oil administration through the nostrils with their head slightly tilted back and a towel placed under their neck. Perform face and head massages (Mukha and Shirbhyanga) with oil after that. Mild steam should be applied to the face and head after abhyanga. Even though providing Steam to the head is prohibited, light steam (Mridu Swedan) can be given to remove impurities and cause the bodily humor (dosa) to liquefy. After performing a sedan on the head, gently massage the neck and shoulders.\n\n➢ Main procedure (Pradhanakarma)\n\nOnce the patient is comfortable with their arms and legs extended, their head is lowered a bit, and their eyes are covered with a cloth. Then slowly pour eight drops of oil. Give the patient mild steam repeated on the cheeks, forehead, hands, and feet. after delivering oil administration through the nostrils. Then, continually tell the patient to spit the oil that entered their throat into a vessel. It is not advisable to swallow medicine that enters the digestive system.\n\n➢ After the procedure (Panchakarma)\n\nGive the patient warm water to rinse their mouth and throat after spitting the drug out of their throat. then counsel medicated smoke (Dhoompana) to rinse his mouth and throat so that the clear bodily humor (dosa) can leave. after waiting for five to ten minutes.\n\nIntervention modification - Any negative side effects will have noticed and reported to the ethical committee. The harmful effect will be treated for the patients. The reason for ending the treatment shall be stated if participants choose to withdraw.\n\nOutcomes - To compare the efficacy of Mashadi tail Oil administration through nostrils and Erandadi tail Oil administration through nostrils with criteria like Range of Motion, VAS, and Neck Disability Index.\n\nA. Range of Motion16\n\nRange of motion.\n\nB. Visual Analogue Scale: -\n\nOn a scale of 0 (no pain) to 10 (worst pain), the patient will be asked to rate their level of discomfort (Figure 4).\n\n\n\nC. Neck Disability Index17\n\n\n\nGantt chart.\n\nFormula Using Mean Difference\n\nPrimary Variable = Flexion (degree)\n\n(Mean) value of flexion for Mashadi tail treatment group (Before) = 31.77 (As Per Reference article)\n\n(Mean) value of flexion for Mashadi tail treatment group (After) = 50. (As Per Reference article).\n\nMean Difference for the effect in flexion after & before 50-31.77 = 18.23\n\nStandard Deviation = 3.821 (As Per Reference article)\n\nConsidering 15 % clinically relevant margin for experimental group δ = (18.23 *15) /100 = 2.7345.n1=n2=21.96+0.8423.82122.73452=30pergroup\n\nConsidering 10% drop out = 3\n\nTotal sample size required = 30 +3 = 33 per group.\n\nThe Mahatma Gandhi Ayurveda College, Hospital & Research Center, Salad (H), will choose patients for Cervical Spondylosis from the OPD and IPD of Panchakarma as well as from specialized periphery camps. For the trial, a total of 60 participants will be enrolled.\n\nAllocation sequence generation – computer-generated random numbers.\n\nAllocation implementation – Participants will be enrolled, given an intervention, and given an allocation sequence by the researcher or the original author.\n\nBlinding – double-blind superiority clinical trial.\n\n\n\n1. Ayurveda Samhitas\n\n2. Modern texts\n\n3. Online search- Google Scholar, etc.\n\n4. Mashadi tail Oil administration through nostrils\n\n5. Erandadi tail Oil administration through nostrils\n\n6. Case record form\n\n7. Patient information\n\n8. Written and informed consent form\n\n9. Measuring scale\n\n10. Sphygmomanometer\n\n11. Goniometer\n\n12. Nasal dropper\n\nPosology.\n\nDrug collection/authentication\n\nThe department of Dravyaguna and Rasashastra of M.G.A.C.H. and RC, Salod, Wardha will validate and identify the drug's raw material before it is obtained from a trustworthy source.\n\nStatistics outcome\n\nFollowing the study, the data will be examined using the appropriate statistical test.\n\nData Analysis (Statistical Methods)\n\nAn inferential statistical test will be used to examine the acquired data.\n\n\nDiscussion\n\nCervical Spondylosis is a condition that affects the cervical area. Pain, stiffness, and limited cervical movement are some of its symptoms. One of the panchakarma procedures is Oil administration through the nostrils, which involves applying medicated oil, decoction (qwath), and buttermilk (Gruta) through the nose. For a total of seven days, the 30 patients undergo Masahdi Tail Oil administration through nostrils (8 bindu in each nostril).\n\nConclusion - Erandadi oil nasal administration may be more effective than Mashadi oil nasal administration in treating Cervical Spondylosis while having fewer adverse effects.\n\nEthical consideration – After receiving approval from the I.E.C. of the Mahatma Gandhi Ayurveda College, Hospital and Research Centre, Salod(H), the study will begin. also following CTRI registration. No. of reference CTRI/2023/03/050923\n\nThe committee will select the trial's endpoint and monitor its execution.\n\nAny negative incident will be evaluated by the researcher and submitted to the ethics committee.\n\nConsent - Before starting the studies, the patients' agreement will be obtained after a thorough explanation of the study's objectives. Trial participants' consent will be obtained by the researcher.\n\nBefore, during, and after the experiment, the participants' private information will be gathered and maintained in confidence. The researcher will be the only person with access to the physical data, which will be maintained in a safe place. Computerized data will be stored on a password-protected hard drive that will only be accessible to the researcher.\n\nDissemination – This protocol will also be made available as a thesis to spread the word about the research for cervical spondylosis. A thorough explanation of the study's methodology, data-gathering techniques, data-processing strategy, and ethical considerations is provided in the study protocol. We want to increase the body of knowledge in this area and make it easier for future studies by spreading our procedure.\n\nStudy status - Now we are in the screening phase of the patients for the above study.\n\nZenodo. SPIRIT Checklist for study. DOI: https://doi.org/10.5281/zenodo.8173935.\n\nLicense: Creative Commons Attribution 4.0 International",
"appendix": "Data availability\n\nNo supporting information is available for this article.\n\n\nAcknowledgments\n\nThe experts whose works are cited and discussed in the manuscripts are acknowledged by the writers for their significant assistance. The writers also acknowledge the writers, editors, and publishers of all the articles, and books, to evaluate and debate the material for this project. They also used journals.\n\n\nReferences\n\nVerma VK, Parwe S, Nisargandha M: Comparative Assessment of Kukkutanda Pinda Sweda and Patra Pinda Sweda in the Management of Cervical Spondylosis (Cervical Spondylosis)-A Study Protocol.\n\nKatkar SR, Pawar V, Shinde DL: CONCEPTUAL STUDY OF MASHADI TAILA OIL ADMINISTRATION THROUGH NOSTRILSIN MANYA STAMBHA WITH SPECIAL REFERENCE TO SHARANGDHAR SAMHITA.2019.\n\nJain M, Parwe S, Ade V, et al.: Study of Nidan (Etiological Factors) Responsible For Cervical Spondylosis With Respect To Cervical Spondylosis in Present Era–A Study Protocol. Journal of Pharmaceutical Research International. 2021; 59–64. Publisher Full Text\n\nhttp\n\nhttp\n\nSamhita S: Acharya ambikadattashashtri, chaukhamba Sanskrit prakashan- Varanasi. Edition-2007. Chikitsasthan, chapter no. 5, PV Sharma.2: 32.\n\nAshtanga hridayam, brahmanandtripathi, chaukhamba Sanskrit pratisthan- delhi, reprint edition- 2017. Sutra sthan chapter 20/1-2.244.\n\nSawarkar P, Deshmukh M, Sawarkar G, et al.: A comparative efficacy study of the panchtikta ghrita matra vasti and panchtikta ghrita marsha Oil administration through nostrils in cervical spondylosis. International Journal of Ayurvedic Medicine. 2020; 11(2): 218–227. Publisher Full Text\n\nParwe SD, Rajput D, Tadas VR, et al.: Efficacy of in Kukkutanda Upanaha Sweda Manyasthambha (Cervical Spondylosis). Journal of Indian System of Medicine. 2018; 6(2): 62.\n\nJain M, Parwe S, Ade V, et al.: Study of Nidan (Etiological Factors) Responsible For Cervical Spondylosis With Respect To Cervical Spondylosis in Present Era–A Study Protocol. Journal of Pharmaceutical Research International. 2021; 59–64. Publisher Full Text\n\nAshtanga hridayam, brahmanandtripathi, chaukhamba Sanskrit pratisthan- delhi, reprint edition- 2017. Sutra sthan chapter 20/1-2.244.\n\nNeville MC: Calcium secretion into milk. J. Mammary Gland Biol. Neoplasia. 2005; 10: 119–128. Publisher Full Text\n\nhttp\n\nSamhita C: Acharya vidhyadhar shukla, chaukhaba Sanskrit pratishthan- delhi. Edition-2015. Siddhisthan chapter 2/22.895.\n\nSamhita C: Acharya vidhyadhar shukla, chaukhaba Sanskrit pratishthan- delhi. Edition-2015. Siddhisthan chapter 2/20.768.\n\nSwartz EE, Floyd RT, Cendoma M: Cervical spine functional anatomy and the biomechanics of injury due to compressive loading. J. Athl. Train. 2005; 40(3): 155–161. PubMed Abstract\n\nMcCarthy MJ, Grevitt MP, Silcocks P, et al.: The reliability of the Vernon and Mior neck disability index, and its validity compared with the short form-36 health survey questionnaire. European spine journal: official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2007; 16(12): 2111–2117. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "283983",
"date": "21 Jun 2024",
"name": "Vineeta Kumari Negi",
"expertise": [
"Reviewer Expertise Musculoskeletal disorders",
"Anorectal disease 9eg Haemorrhoids",
"Fistula",
"Sinus)",
"Pain management",
"Wound 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\nTitle: Instead of Tinospora cordifolia & Ricinus communis write the name of both the oils, as TC & RC are just one of the contents/ingredients of both the types of oils. Write according to PICOT.\nRationale: Not mentioned.\nObjectives: Fewer the better, not mentioned which is your primary objective & which is your secondary objective. As sample size calculation is usually based on your primary objective.\nSample Size Calculation: What is the basis of sample size calculation? Usually we calculate the sample size on the basis of Primary Objective.\nDrug: One should have Content of Drug Analysis/oil to be used in trial, therefore elaborate on this.\n\nAge Group of samples; If it is Cervical Spondylosis then it is a degenerative disease, then how would you justify for the age of 20's.\nStudy Instruments & variables: Clearly define it.\nAnalysis Part: \"depends on objective & study plan\" therefore clearly define your objectives and study plan.\nStudy site: should be appropriate/ choose one site\nMethodology: Elaborate it\nFew more things: Please mention the criteria for discontinuing trial participants and strategies to improve adherence to intervention protocols and procedures for monitoring adherence.\nPlease clarify regarding concomitant care and intervention that will be permitted or prohibited during the trial period.\n\nIs the rationale for, and objectives of, the study clearly described? No\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? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-83
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https://f1000research.com/articles/12-402/v1
|
14 Apr 23
|
{
"type": "Review",
"title": "Anticancer activities of tocotrienols: A Systematic Scoping Review",
"authors": [
"Shaza M Mohamedahmed",
"Muhamad Noor Alfarizal Kamarudin",
"Premdass Ramdas",
"Ali Qusay Khalid",
"Usha Sundralingam",
"Ammu Kutty Radhakrishnan",
"Shaza M Mohamedahmed",
"Muhamad Noor Alfarizal Kamarudin",
"Premdass Ramdas",
"Ali Qusay Khalid",
"Usha Sundralingam"
],
"abstract": "Background: The increasing number of cancer cases requires developing newer approaches to treat this disease. One approach uses natural compounds with known anticancer effects, such as tocotrienols. Many cell-based and animal-model studies found that tocotrienols possess potent anticancer activities. However, the exact molecular regulatory mechanism through which tocotrienols exert anticancer actions remains unclear. Methods: This scoping review analysed data from original research articles reporting on the anticancer effects of tocotrienols on human cancer cell lines published in the last seven years (January 2015 and September 2021) using a systematic scoping review approach. From the initial 619 research papers [ProQuest (n= 61), PubMed (n= 84), Embase (n = 148), Ovid Medline (n =53), Scopus (n = 137), Web of Science (n =136)] identified using pre-defined keywords, only 37 articles met the inclusion and exclusion criteria for this review. Human cancers commonly studied in the 37 research articles include breast, lung, prostate and colorectal cancer cell lines. Results: The analysis showed that exposing human cancer cell lines to tocotrienols triggered common anticancer mechanisms such as activation of apoptosis and inhibition of proliferation, angiogenesis and cell migration through regulation of key regulatory genes and proteins involved in these pathways. Conclusions: The findings show that tocotrienols regulate a number of biomarkers that induce cell death and regulate cell cycle in various types of human cancer cells. Further targeted studies are required to map the definite pathways by which T3 exerts their action and to better understand the cellular actions and the regulatory pathways.",
"keywords": [
"human cancers",
"vitamin E",
"tocotrienols",
"anticancer mechanisms",
"Vitamin E",
"C",
"D",
"Genomics",
"Biomarkers"
],
"content": "Introduction\n\nCancers are the second leading cause of death worldwide before age seventy.1 Cancers may be formed due to gene mutations or critical dysregulation of different cellular survival and death mechanisms,2 usually caused by injurious agents that affect cellular homeostasis, structures, and organelles. Some of the more lethal cellular disruptions are associated with an injury to the plasma membrane, the mitochondria, the endoplasmic membrane and the nucleus,3 which can lead to the development of malignancies. Regardless of the advanced management and treatment available, the number of cancer cases reported is steadily increasing.1 Treating cancers can be complicated as treatments are generally tailored to each patient's needs and health circumstances, including the cancer origin, position, lymph node involvement and metastasis. Cancer treatments are broadly categorized based on the main method of treatment, such as surgical resection, chemotherapy, radiotherapy and hormonal therapy.4 Most of the therapeutic approaches currently used have well documented complications. For instance, the surgical approach requires hospitalization and wound healing time, including the possibility of experiencing common post-surgical complications. Chemotherapeutics drugs are cytotoxic to most living cells (normal or malignant), causing side effects such as hair loss, fatigue, nausea, different vital organs toxicity and potentially, the of developing drug resistance. Hormonal therapies, on the other hand, increase susceptibility to other cancers along with other complications such as gynecomastia and hirsutism. Hence, the need for newer ways to treat and/or prevent cancer which do not pose as many side effects as observed with current therapies or have the ability to decrease the severity of these side effects.\n\nThe evidence in the literature suggests that several natural compounds such as phytochemicals and vitamins are rapidly emerging as promising anticancer agents, where these compounds can be used as therapeutic or adjuvant agents to treat cancers.5 Examples of phytochemicals include isoprenoid derivatives, phenol compounds, carbohydrate derivatives, fatty acids, amino acids, and minerals. In addition, several studies have reported that plant phytochemicals promote immunity, protect against DNA damage, and regulate cell cycle and proliferation.5 Vitamin E (Vit E) is a naturally occurring phytochemical that can exist as two isoprenoid derivatives, tocotrienols (T3) and tocopherols (TP). Tocotrienols and TP have similar chemical structures. However, the side chain on TP is saturated, while the side chain of T3 contains three unsaturated bonds. In addition, both TPs and T3 can be found in four distinctive isoforms known as alpha (α), beta (β), delta (δ) and gamma (γ), which are classified based on the position of methyl groups on the chromanol ring of vitamin E. Natural sources of T3 include palm oil,6–8 annatto seeds9 and rice bran,10,11 while TP can be found in olive oil, soy oil and corn oil (Table 1).\n\nThe T3 possess potent antioxidant, cardioprotective, neuroprotective and anticancer activities, reported in many in vitro and in vivo studies.12 Tocotrienols exert anticancer effects mainly through differentially regulating molecular targets responsible for programmed cell death (PCD) signals, angiogenesis and metastasis.13 The anticancer activity of T3 have been demonstrated in several types of cancers, including breast cancer (BC),14,15 pancreatic cancer,16,17 hepatic cancer,18,19 haematological cancer20,21 and melanoma.22,23 The cytotoxic effects of T3 against cancer cells are triggered via activation of various intracellular signalling pathways such as activation of apoptosis (programmed cell death type I), autophagy (programmed cell death type II), regulation of cell cycle through inhibiting cell cycle progression through cyclin kinase-dependent (CDK), and cyclin D1, and suppression of angiogenesis. Furthermore, T3, may synergize with chemotherapeutic drugs such as statins,24 celecoxib25 and tamoxifen,26,27 to augment their efficacy. Combinations of T3 and natural dietary compounds such as ferulic acid (FA) or jerantinine was reported to induce higher anticancer effects.28,29 The cytotoxic effects of T3 on cancer cells suggest that these molecules can potentially be used as an effective tool in cancer treatment.\n\nThe aim of this scoping review is to understand the cellular actions and the regulatory pathways on how tocotrienols induce anticancer effects in human cancer cells through analysing the genes and proteins that are commonly affected in these cancer cells following exposure to tocotrienols in research articles published between January 2015 to September 2021.\n\n\nMethods\n\nThis review was carried out according to the guidelines of the Preferred Reporting Items For Systematic Review And Meta-Analysis (PRISMA).30 Six databases (PubMed, Pro-Quest, Web of Science, Scopus, Ovid Medline and Embase) were searched using Medical Subject Heading (MeSh) and keywords “tumor*”, “gene*”, “protein*”, “tocotrienol*”, “neoplasm”, “cancer,” and “cell line”. Papers reporting on the effects of T3 on various types of human cancer cell lines, with the primary outcome being gene modulation, regulation or amplification and protein dysregulation, were selected for analysis. In addition, the search was restricted to papers published in English in the last five years (January 2015 to September 2021) to use the latest evidence for this study.\n\nEligible studies were selected based on the study’s inclusion and exclusion criteria. The inclusion criteria include that the paper must (i) be an original research article reporting on human cancer cell line exposed to T3 and the findings were compared with untreated cells; (ii) reported on the effects of T3 using differential expression genes or proteins. The exclusion criteria were (i) studies, where cancer cells were not directly exposed to T3; (ii) the effects of T3 on the human cancer cells did not report on gene or protein regulation; (iii) in vivo studies; (iv) in silico studies.\n\nTwo step screening approach was used to identify suitable articles. Original articles published up to 30 Sept 2021 were included in the analysis. The articles identified from the six databases (PubMed, Pro-Quest, Web of Science, Scopus, Ovid Medline & Embase) were imported and compiled in Endnote software31 initially to eliminate any duplicate articles, and then the articles were uploaded into Covidence software,32 an online software used to carry out systematic reviews. The steps used to review imported research articles using the Covidence software is similar to what researchers would do if they were screening the identified research articles manually. Briefly, in the first screening, the title and abstract of each research article was screened to identify suitable articles. Following this, a full text review was performed on the short-listed articles to further narrow the search. In each screening step, two researchers independently screening steps, and any arising conflicts were resolved by a third independent researcher. Then, data extraction was performed using an Excel template. The following data were extracted from each article: origin and type of cancer cell line, dose, duration and type of tocotrienol or tocotrienol isomers the cancer cells were exposed to, gene and protein modulation, regulation or expression as the primary outcome and other outcomes such as (apoptosis, cell cycle arrest, IC50), and, the bibliographic details of the article (e.g., authors, year of publication, journal name).\n\n\nResults\n\nThe search yielded a total of 619 records from six databases [ProQuest (n= 61), PubMed (n= 84), Embase (n = 148), Ovid Medline (n =53), Scopus (n = 137), Web of Science (n =136)]. The articles were imported into Endnote, a referencing software and after removal of duplicate articles (n=145) from the six databases, there were 474 articles left (Figure 1). These 474 records were uploaded to Covidence, an online software (www.covidence.com) that enables researchers to independently screen and review articles. In Covidence, another 151 duplicate articles were identified and removed from the pool, which left 323 articles in the pool. From the title and abstract screening, based on the inclusion and exclusion criteria, a total of 252 articles were excluded. The remaining 96 articles were subjected to full text review, where 59 articles were excluded, leaving a total of 37 studies (Table 2) that were eligible for data extraction (Figure 1). Data were extracted using a MS-Excel sheet, and information such as origin and type of cancer cell line, dose, duration and type of T3 used and year of publication were collected (Table 2). More than half of the research papers were published in the years 2015, 2016 and 2017 (53%) (Figure 2A). Interestingly half of the reported studies were conducted in China and the United States of America (Figure 2B)\n\n\n\n• Anti-proliferative effects due to oxidative distress activation.\n\n• Regulated at the protein level\n\n\n\n• ↓ Ras/PI3K/Akt/NF-κB and Ras/Raf/ERK/NF-κB pathways responsible for cholesterol synthesis\n\n• Suppression of HMGCR and GLO1 by inactivation of Ras/PI3K/Akt/NF-κB and Ras/Raf/aERK/NF-κB pathways\n\n\n\n• Dose-dependent inhibition of mammospheres from 1-5 μg/mL\n\n• At 5 μg/mL, the growth of the sphere was completely inhibited\n\n• Inhibition of SHP2 in a dose-dependent manner and downstream regulation of RAS/ERK pathway\n\n\n\n• Caused G1 arrest in the cell cycle,\n\n• Induced apoptosis\n\n• Inhibited phosphorylation/activation of Src and Stat3 in a dose-dependent manner\n\n\n\n• Reduced c-Myc.\n\n• No change in Myc regulation or cMyc mRNA levels\n\n• Inhibition in PI3K/AKT/mTOR and RAS/MEK/ERK signalling pathways.\n\n\n\n• δT3 induced dose- and time-dependent apoptotic and anti-proliferative effects on human colorectal cancer cells.\n\n\n\n• δT3 IC50: 50 μM for MiaPaCa-2 cells\n\n• δT3 regulation of EGR-1 is mediated by JNK-c-Jun signalling pathway.\n\n• In the presence of δT3, EGR-1 induces the expression of Bax (a proapoptotic protein), permitting δT3-induced apoptosis\n\n\n\n• Induced autophagic cell death signals\n\n• Endo reticulum triggered apoptosis.\n\n\n\n• Inhibition of cell proliferation and in- duction of apoptosis in TNBC\n\n\n\n• IC50 estimated btw 15-20 μM for γT3 & δT3\n\n• Down - regulating upstream signalling genes and proteins of Ras-Raf-MEK-MEK pathway\n\n\n\n• The number of genes regulated by different T3s isomers are γT3;(177 genes), δ T3;(147 genes) b α T3; (21 genes).\n\n• T3 isomers and TRF activated a proapoptotic effect in Hela cells as early as 12 hours (10 μg/ml).\n\n• Endo-reticulum mediated apoptosis\n\n\n\n• FA alone did not inhibit DLD-1 cells proliferation\n\n• Combined FA and δ T3 decreased the expression of hTERT more than δ T3 alone\n\n\n\n• δ-T3 activated the transcription of endogenous genes known to be under the control of ERα.\n\n• Inhibited the proliferation of both ER+ and ER- BC.\n\n\n\n• 10-20 μg/mL of δ-T3 is cytotoxic to BLM and A375 melanoma cell lines (24hrs-48hrs)\n\n• Induction of apoptosis via activation of ER stress in melanoma cells\n\n\n\n• δT3 & jerantinine B induced concurrent synergistic inhibition of cancer cell growth.\n\n\n\n• γT3 enhanced capecitabine apoptotic activity.\n\n\n\n• The IC50; ±8 and 49±15μM forα-, δT3 and γT3, respectively, for 24 hrs.\n\n• δT3 exhibited more potent cytotoxic effects.\n\n• Cell cycle arrest.\n\n\n\n• IC50 for δ-T3 was (8.04 μg/mL)\n\n• δ-T3 significantly regulated the expression of several genes that promote and regulate apoptosis\n\n\n\n• A dose-dependent decrease in cell growth, cell migration, tumour invasiveness, induction of apoptosis\n\n• inhibition of NF-κB activity, and NF-κB target proteins\n\n\n\n• Cell cycle arrest at G0/G1\n\n• Induction of apoptosis\n\n\n\n• Reduced H2O2-induced lipid peroxidation in a dose-dependent manner.\n\n• Increase the expression of the DNA repair gene MLH1.\n\n• DNMT1 expression and global methylation were positively affected,\n\n• LINE-1 Methylation induction\n\n\n\n• Inhibition of hypoxic adaptation of PC3 stem-like cells in vitro\n\n\n\n• δT3 suppressed cell migration, invasion, and adhesion in dose dependent manner in both cell lines\n\n\n\n• Inhibition of proliferation, migration & invasion in both cell lines\n\n\n\n• upregulation of ceramide\n\n• Induction of apoptosis\n\n\n\n• IC 50 = 5 μM for MD-MB-231, and 4 μM for MCF-7, in dose dependent manner\n\n• reduction in the aerobic glycolysis, reduction in glucose metabolism and glycolytic enzymes HKII, PFKP, PK-M2 and LDH.\n\n\n\n• Apoptotic cell death in different colon cancer cell lines\n\n• Chemopreventive\n\n\n\n• Inhibition of NF-κB pathway\n\n\n\n• Upregulation of Ang-1\n\n• Tie-2 inhibitor increased the cytotoxic effect of γT3\n\n\n\n• γT3 is a proteasome inhibitor\n\n\n\n• Activation of apoptosis in both cell lines. (RAF/RAS/ERK pathway)\n\n\n\n• IC50 αT3: 15 ± 0.4 μM; IC50 αT3-loaded NLC: 10 ± 0.6 μM\n\n• synergistic inhibition of cancer cell growth\n\n\n\n• mitochondrial activity reduction and O2 consumption\n\n• δ-TT-mediated apoptosis, paraptosis and autophagy in PC3 cells\n\n\n\n• Activation of apoptosis through a p53-independent apoptotic pathway\n\n\n\n• Decrease drug resistance in MCF-7/Adr cells\n\n\n\n• Cell cycle arrest in CNE1 cells via the NF- B signalling pathway.\n\n• Induction of apoptosis.\n\nTwelve types of human cancer cell lines were used in the 37 short-listed studies and these include breast cancer,14,26,33–40 prostate cancer,9,11,41–44 lung cancer,10,45 nasopharyngeal cancer,46 hepatocellular carcinoma (liver cancer),47–49 blood cancer,50,51 melanoma], cervical cancer,33,40,54 colorectal cancer,55–60 gastric cancer,61,62 brain cancer57 and pancreatic cancer63 (Figure 2C). The top three human cancer cell lines studied appear to be breast, pancreatic cancer, and colorectal cancers (Figure 2C), while nasopharyngeal and brain cancers were the least studied cancer.\n\nThe different isoforms of T3 used in these studies showed prominent anticancer activities (Figure 2D). While most studies used gamma-T3 (γT3) and/or delta-T3 (δT3) from different sources, only one study investigated the effect of beta-T3 (βT3) (Figure 2D). That could be due to the relatively stronger anticancer potential of γT3 and δT3 and/or because of the very low concentration of βT3 in nature.\n\nIn general, some of the molecular targets and pathways affected by T3 in humans cancer cell lines appear to be common regardless of the type of the malignancy, such as induction of cell death through apoptosis,9,10,26,33,38,40,42,44–46,49–52,54–57,61,63–65 followed by inhibiting proliferation through inhibition of cell cycle9–11,26,34,35,37,40,43,45–49,54–57,60,61,65 or inhibition of angiogenesis,43,60 cell migration and invasion10,45,60,62,65 (Figure 3). In a smaller number of studies, the T3 appear to exert the anticancer effects through antiglycolytic effect,36 suppressing cancer stem cells,33 antioxidant and synergism with other compounds and antineoplastic therapeutic drugs.50 A large number of genes and proteins were differentially regulated in the human cancer cells exposed to various forms of T3. We identified 43 biomarkers (genes and proteins) that were reported in two studies or more (Table 2). Gamma and delta-T3 appear to regulate the expression of most of these genes/proteins (Figure 4).\n\n(TRF: tocotrienol-rich fraction; αT3: alpha-T3, βT3: beta-T3; δT3: delta-T3, γT3: gamma-T3; T3: tocotrienol)\n\nThe pathway enrichment analysis of these 43 biomarkers was carried out using the Metascape bioinformatic tool66 (https://metascape.org/gp/index.html) (Figure 5). According to the software developers, this software can utilize all genes in the genome for the enrichment background.66 In addition, the software employs several gene ontology sources, including the KEGG pathway, GO Biological Processes, Reactome Gene Sets, PANTHER Pathway CORUM, Wiki Pathways and Canonical Pathways to provide the protein-protein interactions (PPI). To perform the analysis, the 43 biomarkers were uploaded into Metascape. The highest expressed 20 clusters based on enriched terms were used to extract biological information based on their molecular functions and disease bio-pathways curated from KEGG databases, WikiPathways and GO Biological Processes (Figure 5A). Biomarkers with a p-value < 0.01, a minimum count of 3, and an enrichment factor > 1.5 were collected and congregated into clusters according to their membership similarities (Figure 5B and 5C). The kappa scores were used to execute hierarchical clustering on the enriched terms and sub-trees (similarity of > 0.3 are considered a cluster). The cluster name represents the most statistically significant term in the cluster (Figure 5C). The top biological pathways identified in this analysis were cancer pathway followed by apoptosis, gastrin signalling pathway, prostate cancer and VEGFA-VEGFR2 signalling pathway (Figure 5B). The apoptosis pathway contained 23 of the identified genes (PARP1, AKT1, XIAP, BIRC5, FAS, ATF4, BAD, BAX, BCL2, CASP3, CASP8, CASP9, GADD45A, DDIT3, ERN1, HRAS, JUN, PIK3CA, MAPK1, MAPK3, MAPK8, TP53, TUBA1C, CDKN1A, MMP9, MYC, RB1, SRC, GSK3B, RAC1, XBP1, CRK, MTOR, HLA-A, RAC2, CCND1, NFKB2, PRKAA1, LONP1, PSEN2, CDK4, CDKN1B, GSN, DYNC1I2, PTPN6, PTPN11, NOTCH1) while the Gastrin signalling pathway contained 20 genes (AKT1, BIRC5, BAD, CCND1, CASP3, CDKN1A, CDKN1B, CRK, MTOR, GSK3B, HRAS, JUN, MYC, PIK3CA, MAPK1, MAPK3, MAPK8, PTPN11, RAC1, SRC, TP53, BAX, CASP9, ATF4, BCL2, PSEN2, PTPN6, PRKAA1, XIAP, PGR, RB1, RAC2, XBP1, CDK4, GADD45A, DDIT3, HES1, NFKB2, ELF2, PRKAG1, CASP8, MMP9, GSN, ERN1, EPHB2, FAS, PARP1, ATP1A3, TUBA1C, HLA-A, EEF1A1, DYNC1I2, GDF10, NOTCH1) and the VEGFA-VEGFR2 signalling pathway had 24 genes (AKT1, BIRC5, FAS, ATF4, CCND1, BCL2, CRK, EPHB2, ERN1, MTOR, GSK3B, HRAS, JUN, PIK3CA, PRKAA1, MAPK1, MAPK3, MAPK8, PTPN6, PTPN11, RAC1, SET, SRC, TUBA1C). The genes in the VEGFA-VEGFR2 signalling pathway were essential in the regulation of angiogenesis and proliferation of cells.67 Some of the molecular targets that reported to be involved in angiogenesis and cell survival such as AKT1, VGF2, CCND1& HRAS were significantly downregulated by T3 in the human cancer cells.\n\n(A) shows a bar graph of enriched terms across input gene lists, colored by p-values, as shown on the sidebar, while (B) and (C) are protein-protein interaction (PPI) enrichment analysis of the molecular complex detection (MCODE) algorithm has been identified for individual gene lists have been gathered and are shown in (B) the three best-scoring terms by p-value are the functional description of the corresponding components genes are shown in the figure. In (C) MCODE1 represents Chromosomal and microsatellite instability in colorectal cancer and cancer pathways); MCODE2 represents PI3K-AKT-mTOR signaling pathway and therapeutic opportunities and cancer pathways; and MCODE3 represents apoptosis and cancer pathways). The size of the node is related to the protein p-value.\n\nUtilizing the highest ten enrichment analysis pathways that were carried out using KEGG (log P is between -42.7857 and -30.1946) 40 common genes i.e. represented in more than two pathways were selected for protein-protein interaction (PPI) analysis. The 40 proteins were uploaded into an online database that can be used for PPI known as the STRING database ( https://string-db.org). Mapping of the 40 genes showed 40 nodes (interactions) along with 225 edges and 63 expected edges with PPI enrichment p-value:< 1.0e-16 analysed at high confidence (0.700) minimum required interaction score. The selected proteins formed three clusters that contained 21,12 and 7 proteins (Figure 6). The top molecular functional processes with the highest strength were used to determine the functions associated with the annotated proteins. The top functional processes were identified to be histone deacetylase regulator activity (GO:0035033; p= 0.0039, strength: 2.39), cysteine-type endopeptidase activity involved in apoptotic signalling pathway (GO:0097199; p=0.00017; strength: 2.26), BH3 domain binding (GO:0051434; p=0.0064; strength: 2.21), cyclin-dependent protein serine/threonine kinase inhibitor activity (GO:0004861; p=0.00038; strength: 2.09) and MAP kinase activity(GO:0004707; p=0.0011; strength: 1.87). Interestingly, all the molecular functions that regulated initiator cell death were found in one cluster, which includes the mammalian family of mitogen-activated protein kinases (MAPK 1,3 and 8), the caspase family proteins CASP 3,8 and 9, and some cell cycle regulators such as CDK4, CDKN1B and CDKN1A (Figure 6). Based on the STRING analysis, the mammalian family of MAPK appear to be important targets for T3s to exert their anticancer activity, which is in sync with their pro-apoptotic and cell cycle dysregulation activities. However, MAPKs activity is subjective to the type of the malignancies, and their microenvironment, as these have been found to have dual effects as oncogenes and tumour suppressors in some cancers and related microenvironment.68,69\n\nThe dotted line indicates the interactions among the proteins in the three clusters.\n\n\nDiscussion\n\nThe potent cytotoxic effect of T3s is explored and evident in several cancers, yet the exact route through which this action is expressed is still not fully elucidated. In this scoping review, we attempted to understand how T3 exerted their anticancer activity in human cancers and the regulatory mechanisms that govern the anticancer activities. The findings from this study strongly suggest that the most common means by which T3 mediate their effect were through induction of apoptosis and inhibition of proliferation, angiogenesis, and metastasis.\n\nIn this review, 25 articles reported that T3 promoted anticancer effects through cell cycle arrest and/or dysregulation of pathways that control cell proliferation and death. One such mechanism was through activation of deoxidation due to overexpression of the PRX4 protein, which causes reduction of hydrogen peroxide and alkyl hyperoxide into water and alcohol and activation of NF-kB.47 Another mechanism was the ability of T3 to inhibit the expression of the telomerase reverse transcriptase (TERT) gene in cancer cells. This TERT gene is an essential gene and protein that is involved in cellular proliferation and genetic transcription, which is found in more than 80% of most tumours but not in healthy cells.70 Delta T3 was reported to suppress the expression of the TERT gene in human colorectal cancer cells.56 In addition, the cytotoxic effects of T3 can be mediated by decreasing the expression of the hypoxic inducible factor-1α (HIF-1α) gene in cancer stem cells and in androgen-resistant prostate cancer.41 It should be noted that HIF-1α is highly expressed in many malignancies and this gene is responsible for various regulatory mechanisms, including hypoxia, angiogenesis and cell proliferation.41 The antiproliferative effect of T3 on cancer cells is most likely mediated through suppression of proliferative and cell survival pathways such as the VEGFA-VEGFR2 signalling pathway and RAC1/PAK1/p38/MMP2 pathway and activation of apoptosis.\n\nThe cell cycle consists of four phases; S phase (DNA synthesis) and M phase (mitotic phase), which are set apart by two gaps (G) phases, G1 and G2 (Figure 7). The cell cycle is regulated by cyclins, which are regulatory blocks of cyclin dependent kinases (CDK) that form heterodimers that promote proliferation and govern the cell cycle checkpoints. The CDK regulate genomic and chromosomal activity in many neoplasms leading to the uncontrolled proliferation and tumorigenesis of cancer cells. The cell cycle has many checkpoints and various types of cyclins are synthesized and dispersed at the cell cycle checkpoints. Checkpoints are regulated by CDK-cyclin complex inhibitors such as p16, p18, p21 and p27, which control downstream activation of the cell cycle pathways, where over-expression can result in cell cycle arrest.71 The two crucial checkpoints are (i) after DNA replication midway to the end G1 phase before DNA replication and (ii) at G2 before chromosomal segregation. The first checkpoint is regulated by CCND1, which is the most common CDK, that phosphorylates the retinoblastoma protein (pRB), allowing the cell cycle to progress while unphosphorylated RB suppresses cell proliferation and keeps the cells at G0.72 The CCND1 is overexpressed in several human malignancies such as breast cancer, lung cancer, sarcomas and squamous cells.73 The p21(CDKN1A) and p27 (CDKN1B) are key suppressors of CCND1 and crucial to activating cell cycle arrest at G1.72 Dysregulation of CDKs is an essential feature of many cancers and provides good targets for drug discovery. Over-expression of CDK in several cancers have become essential targets for drug therapy, such as CDK4/6 inhibitors ribociclib and abemaciclib.74,75\n\nT3s regulated the molecular targets demonstrated in this diagram in two or more studies.\n\nIn prostate cancer cells, T3 suppressed proliferation and induced apoptosis through dysregulation of several molecular targets such as NF-κB, AKT, STAT3, p53 and p21.9,11,72,76 The T3 were reported to increase the expression of p21 and p27 and suppress histone deacetylases in human prostate cancer cells.11 Similarly, the anticancer effect of δT3 on nasopharyngeal cancer (NPC) was mediated through several molecular targets, including downregulation of p21 and upregulation of p16, and downregulation of CCND1, CDK2 and CDK4, which caused cell cycle arrest, possibly due to dysregulation of P16/CDK4/CCND1 signalling pathway.46 In this review, we found that the members of the cyclin protein family were often downregulated by T3s regardless of the malignancy origin.11,34,46,49,60 In addition, exposure to T3 caused upregulation of p21 and p27 in several human cancer cell lines11,34,46,55 except in one study, in which γT3 and δT3 suppressed the expression of the p21 gene in cervical cancer cells.40\n\nThe extrinsic pathway of apoptosis is regulated by the death receptors such as the tumour necrosis factor receptors (TNFR), tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and the TNFR superfamily member-6 (TNFRSF6/FAS). These receptors regulate apoptosis, thus, the fate of the cell. The intrinsic pathway of apoptosis is coordinated by the mitochondria and is set in motion by different proteins that mediate and control cellular homeostasis. One of cancer leading survival mechanisms is decreased expression of pro-apoptotic proteins and increased expression of anti-apoptotic proteins.77 An example of that critical pro-survival proteins is the BCL2 family, which inhibits several pro-apoptotic proteins that exhibit the homology domain of the BCL2 protein, such as BAX and BAK. Overexpression of BCL2 in cancers is associated with treatment resistance and poor prognosis.78 Another important protein is the p53 tumour suppressor gene. Lack of p53 allows the progression and proliferation of damaged genetic material. However, activation of p53 upregulates the expression of several genes, such as p21.79 It can also activate BAX, an essential gene regulator of apoptosis in both intrinsic and extrinsic pathways.80,81 In this review, six research articles reported that exposure to T3 increased the expression of p53 and BAX in human cancer cells (Figure 8). In addition, the T3 isoforms inhibited the expression of BCL2 in various cancers triggering the expression of several pro-apoptotic proteins and genes causing cell death.14,37,40,46,51,52 For example, in cervical cancer cells, T3 reduced the expression of BCL2 and induced apoptosis by upregulating BAX and cytochrome C, a cascade of molecular events expressed during mitochondrial apoptotic pathway activation.54 In NPC cells, γT3 decreased the expression of the BCL2 gene and BCL2 protein, which in turn activated BAX2 and upregulated CASP proteins 3,8 and 9, causing activation of both apoptotic pathways.46 FAS, a membrane protein belonging to the death receptors (DR) family, can induce apoptosis by triggering the caspase cascades (Figure 8). It was reported that exposure to δ-T3 induced cytotoxic cell death in chronic amyloid leukaemia that was mediated by the overexpression of FAS and activation of the extrinsic apoptotic pathway, among other reported genes that are related to the activation of apoptosis.51 The pro-apoptotic activity of T3 can be mediated through action on different molecular targets that regulate apoptotic cell death (Figure 8).\n\nOne of the primary mechanisms through which solid tumours survive is their ability to form new vasculature and, thus, gain the ability to proliferate at a higher rate and migrate to a suitable microenvironment. Forming new vessels (angiogenesis) is fundamental for tumour proliferation, sustained nourishment, and oxygen supply. Hypoxia-inducible factor (HIF) is a major factor in the activation of angiogenesis and cancerous cell migration, in search for a better microenvironment. Tumours express abundant amounts of HIF, which in turn regulates the vascular endothelial growth factor (VEGF) and the VEGF receptor transcription responsible for new vasculature.82 Several anticancer therapies target the molecular signalling pathways responsible of the formation of new vessels to decrease oxygen and nutrition supply to tumours, which will eventually lead to the death signal’s activation and subsequently killing the cancerous cells. Many known treatments exert their cytotoxic action via these processes, such as Sunitinib inhibitor of VEGF receptor tyrosine kinase activity and Bevacizumab, a selective inhibitor of circulating VEGF used in the treatment of refractory ovarian cancer.83 In this review, the antiangiogenics activity of T3 was among the five most common cellular mechanisms through which T3 exert their actions. Similarly, key molecular targets in tumour angiogenesis, such as HIF1A and VEGFR2, were superseded by T3.\n\nA limitation of this study is that it targeted all types of human cancer cell lines to find common molecular targets and did not target on a single type of human cancer. In addition, the review may have missed papers that did not meet the time scope of this review.\n\n\nConclusions\n\nAs reported by the reviewed studies, T3 regulate several underlying cancer cell death mechanisms in different cancer cell lines. Such as a cell cycle regulator and apoptosis inducers. Further targeted studies are required to map the definite pathways by which T3 exerts their action. The reported potent antineoplastic effects in cell culture-based studies and animal studies invite extensive examination of the common mechanism by which T3 exert their action in order for this promising natural compound clinical use.",
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PubMed Abstract | Publisher Full Text\n\nWang C, Ju H, Shen C, et al.: miR-429 mediates δ-tocotrienol-induced apoptosis in triple-negative breast cancer cells by targeting XIAP. Int. J. Clin. Exp. Med. 2015; 8(9): 15648–15656. PubMed Abstract\n\nRamdas P, Radhakrishnan AK, Abdu Sani AA, et al.: Advancing the role of gamma-tocotrienol as proteasomes inhibitor: A quantitative proteomic analysis of MDA-MB-231 human breast cancer cells. Biomolecules. 2019; 10(1): 19. PubMed Abstract | Publisher Full Text | Free Full Text\n\nComitato R, Guantario B, Leoni G, et al.: Tocotrienols induce endoplasmic reticulum stress and apoptosis in cervical cancer cells. Genes and Nutrition. 2016; 11(1): 32. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaneko S, Sato C, Shiozawa N, et al.: Suppressive effect of delta-tocotrienol on hypoxia adaptation of prostate cancer stem-like cells. Anticancer Res. 2018; 38(3): 1391–1399. PubMed Abstract\n\nFontana F, Raimondi M, Marzagalli M, et al.: Mitochondrial functional and structural impairment is involved in the antitumor activity of δ-tocotrienol in prostate cancer cells. Free Radic. Biol. Med. 2020; 160: 376–390. PubMed Abstract | Publisher Full Text\n\nTang KD, Liu J, Russell PJ, et al.: Gamma-tocotrienol induces apoptosis in prostate cancer cells by targeting the Ang-1/Tie-2 signalling pathway. Int. J. Mol. Sci. 2019; 20(5): 1164. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoore C, Palau VE, Mahboob R, et al.: Upregulation of pERK and c-JUN by γ-tocotrienol and not α-tocopherol are essential to the differential effect on apoptosis in prostate cancer cells. BMC Cancer. 2020; 20(1): 1–10. Publisher Full Text\n\nRajasinghe LD, Pindiprolu RH, Gupta SV: Delta-tocotrienol inhibits non-small-cell lung cancer cell invasion via the inhibition of NF-κB, uPA activator, and MMP-9. Onco. Targets. Ther. 2018; 11: 4301–4314. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShen J, Yang T, Tang Y, et al.: d-Tocotrienol induces apoptosis and inhibits proliferation of nasopharyngeal carcinoma cells. Food and Function. 2021; 12(14): 6374–6388. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbdul Rahman Sazli F, Jubri Z, Abdul Rahman M, et al.: Gamma-tocotrienol treatment increased peroxiredoxin-4 expression in HepG2 liver cancer cell line. BMC Complement. Altern. Med. 2015; 15(1): 1–7.\n\nBurdeos GC, Ito J, Eitsuka T, et al.: δ and γ tocotrienols suppress human hepatocellular carcinoma cell proliferation via regulation of Ras-Raf-MEK-ERK pathway-associated upstream signaling. Food Funct. 2016; 7(10): 4170–4174. PubMed Abstract | Publisher Full Text\n\nTupal A, Sabzichi M, Bazzaz R, et al.: Application of ɑ-tocotrienol-loaded biocompatible precirol in attenuation of doxorubicin dose-dependent behavior in HUH-7 hepatocarcinoma cell line. Nutr. Cancer. 2020; 72(4): 653–661. PubMed Abstract | Publisher Full Text\n\nChen C-C, Liu T-Y, Huang S-P, et al.: Differentiation and apoptosis induction by lovastatin and γ-tocotrienol in HL-60 cells via Ras/ERK/NF-κB and Ras/Akt/NF-κB signaling dependent down-regulation of glyoxalase 1 and HMG-CoA reductase. Cell. Signal. 2015; 27(11): 2182–2190. PubMed Abstract | Publisher Full Text\n\nLee NK, Radhakrishnan AK, Selvaduray KR: Apoptosis gene network regulated by delta-tocotrienol in K562 chronic myeloid leukaemia cells. J. Oil Palm. Res. 2017; 29: 251–261.\n\nMontagnani Marelli M, Marzagalli M, Moretti RM, et al.: Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells. Sci. Rep. 2016; 6(1): 1–14.\n\nRaimondi M, Fontana F, Marzagalli M, et al.: Ca2+ overload- and ROS-associated mitochondrial dysfunction contributes to δ-tocotrienol-mediated paraptosis in melanoma cells. Apoptosis. 2021; 26(5-6): 277–292. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXu W, Mi Y, He P, et al.: γ-Tocotrienol inhibits proliferation and induces apoptosis via the mitochondrial pathway in human cervical cancer HeLa cells. Molecules. 2017; 22(8): 1299. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShibata A, Nakagawa K, Tsuduki T, et al.: δ-Tocotrienol treatment is more effective against hypoxic tumor cells than normoxic cells: potential implications for cancer therapy. J. Nutr. Biochem. 2015; 26(8): 832–840. PubMed Abstract | Publisher Full Text\n\nEitsuka T, Tatewaki N, Nishida H, et al.: A combination of δ-tocotrienol and ferulic acid synergistically inhibits telomerase activity in DLD-1 human colorectal adenocarcinoma cells. J. Nutr. Sci. Vitaminol. 2016; 62(5): 281–287. Publisher Full Text\n\nAbubakar IB, Lim K-H, Kam T-S, et al.: Synergistic cytotoxic effects of combined δ-tocotrienol and jerantinine B on human brain and colon cancers. J. Ethnopharmacol. 2016; 184: 107–118. PubMed Abstract | Publisher Full Text\n\nZappe K, Pointner A, Switzeny OJ, et al.: Counteraction of oxidative stress by vitamin E affects epigenetic regulation by increasing global methylation and gene expression of MLH1 and DNMT1 dose dependently in Caco-2 cells. Oxidative Med. Cell. Longev. 2018; 2018: 1–13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHusain K, Zhang A, Shivers S, et al.: Chemoprevention of azoxymethane-induced colon carcinogenesis by delta-tocotrienol. Cancer Prev. Res. 2019; 12(6): 357–366. PubMed Abstract | Publisher Full Text\n\nPrasad S, Gupta SC, Tyagi AK, et al.: γ-Tocotrienol suppresses growth and sensitises human colorectal tumours to capecitabine in a nude mouse xenograft model by down-regulating multiple molecules. Br. J. Cancer. 2016; 115(7): 814–824. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSun W-G, Song R-P, Wang Y, et al.: γ-Tocotrienol-inhibited cell proliferation of human gastric cancer by regulation of nuclear factor-κB activity. J. Agric. Food Chem. 2018; 67(1): 441–451. PubMed Abstract | Publisher Full Text\n\nZhang YH, Ma K, Liu JR, et al.: γ-tocotrienol inhibits the invasion and migration of human gastric cancer cells through downregulation of cyclooxygenase-2 expression. Oncol. Rep. 2018; 40(2): 999–1007. PubMed Abstract | Publisher Full Text\n\nWang C, Husain K, Zhang A, et al.: EGR-1/Bax pathway plays a role in vitamin E δ-tocotrienol-induced apoptosis in pancreatic cancer cells. J. Nutr. Biochem. 2015; 26(8): 797–807. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRaimondi M, Fontana F, Marzagalli M, et al.: Ca2+ overload-and ROS-associated mitochondrial dysfunction contributes to δ-tocotrienol-mediated paraptosis in melanoma cells. Apoptosis. 2021; 26(5): 277–292. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHusain K, Centeno BA, Coppola D, et al.: D-Tocotrienol, a natural form of vitamin E, inhibits pancreatic cancer stem-like cells and prevents pancreatic cancer metastasis. Oncotarget.\n\nZhou Y, Zhou B, Pache L, et al.: Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 2019; 10(1): 1–10.\n\nAbhinand CS, Raju R, Soumya SJ, et al.: VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J. Cell Commun. Signal. 2016; 10(4): 347–354. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee S, Rauch J, Kolch W: Targeting MAPK signaling in cancer: mechanisms of drug resistance and sensitivity. Int. J. Mol. Sci. 2020; 21(3): 1102. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBraicu C, Buse M, Busuioc C, et al.: A comprehensive review on MAPK: a promising therapeutic target in cancer. Cancers. 2019; 11(10): 1618. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYuan X, Larsson C, Xu D: Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new players. Oncogene. 2019; 38(34): 6172–6183. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAl-hassany HA, Albu-rghaif A, Naji M: Tumor diagnosis by genetic markers protein P-53, p16, C-MYC, N-MYC, protein K-Ras, and gene her-2 Neu is this possible. Pakistan J. Medical Health Sci. 2021; 15(8): 2350–2354. Publisher Full Text\n\nLiu J, Peng Y, Wei W: Cell cycle on the crossroad of tumorigenesis and cancer therapy. Trends Cell Biol. 2021.\n\nMalumbres M, Barbacid M: Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer. 2009; 9(3): 153–166. PubMed Abstract | Publisher Full Text\n\nMartínez-Chávez A, Rosing H, Hillebrand M, et al.: Development and validation of a bioanalytical method for the quantification of the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib in human and mouse matrices using liquid chromatography-tandem mass spectrometry. Anal. Bioanal. Chem. 2019; 411(20): 5331–5345. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBarroso-Sousa R, Shapiro GI, Tolaney SM: Clinical development of the CDK4/6 inhibitors ribociclib and abemaciclib in breast cancer. Breast care. 2016; 11(3): 167–173. PubMed Abstract | Publisher Full Text | Free Full Text\n\nErkisa M, Sariman M, Geyik OG, et al.: Natural products as a promising therapeutic strategy to target cancer stem cells. Curr. Med. Chem. 2022; 29(4): 741–783. PubMed Abstract | Publisher Full Text\n\nGoldar S, Khaniani MS, Derakhshan SM, et al.: Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac. J. Cancer Prev. 2015; 16(6): 2129–2144. Publisher Full Text\n\nMohamed MS, Bishr MK, Almutairi FM, et al.: Inhibitors of apoptosis: clinical implications in cancer. Apoptosis. 2017; 22(12): 1487–1509. Publisher Full Text\n\nFarnebo M, Bykov VJ, Wiman KG: The p53 tumor suppressor: a master regulator of diverse cellular processes and therapeutic target in cancer. Biochem. Biophys. Res. Commun. 2010; 396(1): 85–89. PubMed Abstract | Publisher Full Text\n\nChipuk JE, Kuwana T, Bouchier-Hayes L, et al.: Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004; 303(5660): 1010–1014. PubMed Abstract | Publisher Full Text\n\nWang Y-C, Wang L-T, Hung TI, et al.: Severe cellular stress drives apoptosis through a dual control mechanism independently of p53. Cell Death Dis. 2022; 8(1): 1–5.\n\nFu Z, Yuan Y: The role of tumor neogenesis pipelines in tumor progression and their therapeutic potential. 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}
|
[
{
"id": "192955",
"date": "22 Aug 2023",
"name": "Kok Lun Pang",
"expertise": [
"Reviewer Expertise Pharmacology",
"cancer research",
"pharmacognosy"
],
"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\nShaza et al. reviewed the anticancer activities of tocotrienols over several cancerous cells, followed by a bioinformatics analysis of the regulated genes and proteins. Kindly refer to the comments:\nTitle: Kindly be specific with the \"Systematic\" and \"Scoping review\". They are not the same1.\nAbstract: Please shift the statement \"human cancers commonly studied in the 37 research...\" to the Results section.\nAbbreviations: Please define the abbreviations before using them, and use them consistently throughout the manuscript.\nIntroduction:\nThe justification for the use of natural compounds is not concrete. As the authors claimed that chemotherapeutics drugs are cytotoxic to most living cells, causing side effects, etc., then the authors mentioned the natural compounds as promising anticancer agents. Kindly note that plant bioactive compound is the main source for the current mainstream chemotherapeutic agents2. So it is kind of contradicting each and other.\n\nSome statements are not supported with citations.\n\nTable 1: This is confusing as TRF capsules or mixtures in this table are from palm oil. Please include other sources like vegetables, nuts, etc.\n\nIntroduction: As the authors mentioned the mechanisms and cellular actions of tocotrienol-mediated anticancer activities, then what is the impact/core value of this review? Justification is weak/not available. What is/are the research gaps?\n\nMethods:\nThe search strategy is not clear. Kindly state the searching string including the Boolean commands.\n\nThe authors stated searching was restricted in the last 5 years but stated 7 years in the abstracts.\n\nPlease redo the literature search as the search record was 2 years back. There are several important articles being published ever since 2021.\n\nConfusing exclusion criteria. Exclusion criteria are not simply the opposite of inclusion criteria3.\n\nAre the authors considering the studies that employed the combinational treatment of T3 with other chemicals or compounds?\n\nData extraction: - Who performed the article searching and screening? Who is the 3rd independent researcher? - Please use \"concentration\", not \"dose\"\n\nFig 1: The number of records is not tally. 323 records screened and 252 records removed, and should leave 71 records, not 96. Besides, 96 records exclude 58 records (2+16+7+1+32) and should be 38 records, not 37. Please check.\nResults:\nTable 2: Kindly check the content, please be specific as some (Abubakar et al, 2016) reported the changes of kinetic activities, not protein expression. Please standardise the term writing format as some proteins were written in italicised format (mouse genes?) or full capital letters (human genes?).\n\nTable 3: - is there any difference between ERK and ERK1? Or they should be grouped as 1? - PARP, caspases are total or cleaved form? How about the phosphorylation status, as proteins like AMPK, AKT, CDK, etc are activated or inhibited upon phosphorylation? GO and KEGG pathway analysis are not described in Methods\n\nFig 4, Fig 5 and Fig 6: pathway analysis should be separated for upregulated and downregulated gene or protein set. This is because Metascape and STRING only recognise the gene or protein ID but not their expression or regulation. The authors should run them twice and separate the upregulated and downregulated gene sets and proteins. By performing this, the authors will be able to explain the dual effects of MAPKs, as oncogenes or tumour suppressors.\n\nResults (Protein-protein interaction): How the authors obtained the log P? From the referred studies?\nDiscussion:\nThe authors stated that 25 articles reported the anticancer effects of T3, but the results and Table 1 showed at least 30 articles reporting on the anticancer effects of T3. Kindly correct this.\n\nIs it making sense by combining and analysing the up- or down-regulated proteins or genes from different cancer cells, tocotrienol types and treatment timeframe?\n\nWhat is the contribution or input of GO/KEGG analysis as new knowledge or insights of the anticancer of T3? This will justify whether a GO/KEGG analysis is crucial or beneficial in this review.\n\nFigure 8: Kindly review the content for this figure. For example, T3 overexpressed the FAS, not acting on FAS receptor. Is T3 directly activate the caspases or induce the release of cyt c?\n\nConclusion: Note that the authors only focused on in vitro data. Kindly update the conclusion accordingly.\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": "11684",
"date": "16 Aug 2024",
"name": "Ammu Kutty Radhakrishnan",
"role": "Author Response",
"response": "Reviewer comment: Title: Kindly be specific with the \"Systematic\" and \"Scoping review\". They are not the same. Author's response: Thank you for highlighting this. We know the difference between “Systematic” and “Scoping” reviews. However, the term “systematic scoping” review is an acceptable title for a scoping review, as we have previously published a scoping review with the term \"systematic scoping review\", which implies a systematic method used to undertake this review. We would like the title to remain as it is. Reviewer's comment: Please shift the statement \"human cancers commonly studied in the 37 research...\" to the Results section Author's response: Thank you for highlighting this oversight. We have amended this. Reviewer's comment: Abbreviations: Please define the abbreviations before using them, and use them consistently throughout the manuscript. Author's response: Thank you for highlighting this oversight. We have amended this. Reviewer's comment: The justification for the use of natural compounds is not concrete. As the authors claimed that chemotherapeutic drugs are cytotoxic to most living cells, causing side effects, etc., then the authors mentioned the natural compounds as promising anticancer agents. Kindly note that plant bioactive compound is the main source for the current mainstream chemotherapeutic agents2. So it is kind of contradicting each and other. Author's response: Thank you for highlighting this oversight. We have amended this. Reviewer's comment: Some statements are not supported with citations Author's response: Thank you for highlighting this oversight. We have amended this. Reviewer's comment: Introduction: As the authors mentioned the mechanisms and cellular actions of tocotrienol-mediated anticancer activities, then what is the impact/core value of this review? Justification is weak/not available. What is/are the research gaps? Author's response: Thank you for highlighting this oversight. We have amended this. Reviewer's comment: The search strategy is not clear. Kindly state the searching string, including the Boolean commands. Author's response: Thank you for this comment. We have added the following statement to the paper. The database was searched using the following terms and Boolean commands such as “tumor* OR neoplasm Or cancer” AND “gene(s)” OR “gene* expression” OR “protein(s)” AND “tocotrienol*’ in all databases. Reviewer's comment: The authors stated searching was restricted in the last 5 years but stated 7 years in the abstracts. Author's response: Thank you for pointing this out. It should have been in the last seven years (not five years). This has been amended. Reviewer's comment: Table 1: This is confusing as TRF capsules or mixtures in this table are from palm oil. Please include other sources like vegetables, nuts, etc. Author's response: Thank you for pointing this out. Table 1 will be moved to the results section as this table highlights the sources of tocotrienols that were mainly used in the papers selected for this scoping review. We will amend the introduction and results sections to reflect these changes. Reviewer's comment: Please redo the literature search as the search record was 2 years back. There are several important articles being published ever since 2021. Author's response: We cannot do this as this scoping review as we have stated in the methods section that this scoping review will only use papers published in English in the last seven years (January 2015 to September 2021). Reviewer's comment: Confusing exclusion criteria. Exclusion criteria are not simply the opposite of inclusion criteria Author's response: Thank you for highlighting this. We will include a statement under the “Eligibility criteria” that any papers that did not meet the inclusion criteria will be excluded from this scoping review. Reviewer's comment: Are the authors considering the studies that employed the combinational treatment of T3 with other chemicals or compounds? Author's response: There were a few papers reporting on the combination of T3 and other compounds. However, we only included the effects reported for T3 (results from combination effects were used) as the focus of this paper is to elucidate the genes and proteins modulated by T3 in human cancer cells. Reviewer's comment: Who performed the article searching and screening? Who is the 3rd independent researcher? Author's response: Dr Shaza and Dr Usha independently performed the article search, screening and data extraction. Prof Ammu was the third independent researcher to resolve any arising conflict. The screening and selection of articles were performed using an online platform (Covidence), which allows independent and unbiased selection of the compiled articles by each reviewer and the conflict resolver. Reviewer's comment: Please use \"concentration\", not \"dose\" Author's response: Thank you for the comment. However, we “dose” and “concentration” based on how the authors of the selected papers reported in their paper. Reviewer's comment: Fig 1: The number of records is not tally. 323 records screened and 252 records removed, and should leave 71 records, not 96. Besides, 96 records exclude 58 records (2+16+7+1+32) and should be 38 records, not 37. Please check. Author's response: Thank you for highlighting the oversight. We have checked our data and found an error and we have rectified this. We will upload a revised version of Fig 1. Reviewer's comment: is there any difference between ERK and ERK1? Or should they be grouped as 1? Author's response: We checked the literature and there are at least two forms of extracellular signal-regulated kinase (ERK). In the current manuscript, we reported ERK or ERK1 (Table 3) based on what is reported in each paper. So, we cannot group all the ERK as one. We need to follow what was cited in the respective papers Reviewer's comment: Table 2: Kindly check the content, please be specific as some (Abubakar et al, 2016) reported the changes of kinetic activities, not protein expression. Author's response: We have re-checked the paper (Abubakar et al., 2016) and confirm that the authors reported fold change in terms of expression (Fig 4 page 114 of this paper). Please see an excerpt from the Figure legend provided. “Fig. 4. Induction of caspase 8, 9 and 3 enzymatic activities by individual IC50 dose and combined low-dose treatments of δ-tocotrienol with IC20 dose of jerantinine B on (a, b,c) U87MG and (d, e, f) HT-29 cells. Results are presented as percentage fold increase over untreated control cells. Both individual and combined treatments induce caspase 8 and 3 activation on U87MG and HT-29 cells. Whereas, an increased caspase 9 activity is observed in combined treatments (U87MG and HT-29 cells) and U87MG cells treated with IC50 dose of jerantinine B.” Reviewer's comment: Please standardise the term writing format as some proteins were written in italicised format (mouse genes?) or full capital letters (human genes?). Author's response: Please check the following URL, which states [5]: “Gene symbol usage The HGNC endorses the use of italics to denote genes, alleles and RNAs to distinguish them from proteins.” This paper did not distinguish between human or mouse genes. So, we are not wrong. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494048/#:~:text=Gene%20symbol%20usage,to%20distinguish%20them%20from%20proteins. Reviewer's comment: is there any difference between ERK and ERK1? Or they should be grouped as 1? Author's response: We checked the literature and there are at least two forms of extracellular signal-regulated kinase (ERK). In the current manuscript, we reported ERK or ERK1 (Table 3) based on what is reported in each of the papers. So, we cannot group all the ERK as one. We need to follow what was cited in the respective papers. Reviewer's comment: PARP, caspases are total or cleaved form? How about the phosphorylation status, as proteins like AMPK, AKT, CDK, etc are activated or inhibited upon phosphorylation? Author's response: Table 2 actually provided the information requested by the reviewer. Phosphorylation is indicated by “p” next to the affected protein, while cleavage is indicated by “c”. The abbreviation for “p” is shown at the bottom of Table 2. We just realised that the abbreviation for “c” is missing. Any proteins/genes that were reported to be “upregulated” or “downregulated” are indicated by the ↑ (up) or ↓ (down) symbols. Again, this is indicated at the bottom of Table 2. We will add the abbreviation for “c” to the list at the bottom of this table. Reviewer's comment: GO and KEGG pathway analysis are not described in Methods Author's response: The GO and KEGG pathway analyses are not described in Methods because we did not use these analyses directly. We used another platform known as “Metascape” (https://metascape.org/gp/index.html#/main/step1), which is described in the Methods. Metascape has an in-built link to GO and KEGG. Reviewer's comment: Results (Protein-protein interaction): How the authors obtained the log P? From the referred studies? Author's response:We defined the log P based on bioinformatic software (STRING), which has a functional network analysis that provided this information. Please see a screenshot from the website that provides this information. We hope this clarifies the query. Reviewer's comment: The authors stated that 25 articles reported the anticancer effects of T3, but the results and Table 1 showed at least 30 articles reporting on the anticancer effects of T3. Kindly correct this. Author's response: We think the reviewer did not understand what is presented in Figure 3. We were a total of 37 articles that reported on the anticancer effects of T3, that were selected for this scoping review (Table 2 and Figure). Figure 3 reports on the main mode of action of T3, of which 25 papers reported on apoptosis, 23 on anti-proliferative and cell cycle inhibition, 9 on anti-angiogenesis and 7 on other mechanisms. However, some of these papers reported more than one mode of action of T3 on the cancer cells. Hence, the total number cannot be 37. Reviewer's comment: Is it making sense by combining and analysing the up- or down-regulated proteins or genes from different cancer cells, tocotrienol types and treatment timeframe? Author's response: This is one way of reporting the data. We are not reporting primary data. We are reporting secondary data i.e. extracting information from published papers, which is what a scoping review is all about. Reviewer's comment: What is the contribution or input of GO/KEGG analysis as new knowledge or insights of the anticancer of T3? This will justify whether a GO/KEGG analysis is crucial or beneficial in this review. Author's response: The author's main goal is to compile and review all The GO and KEGG pathway analyses are not described in Methods because we did not use these analyses directly. We used another platform known as “Metascape” (https://metascape.org/gp/index.html#/main/step1), which is described in the Methods. Metascape has an in-built link to GO and KEGG. Reviewer's comment: Figure 8: Kindly review the content for this figure. For example, T3 overexpressed the FAS, not acting on FAS receptor. Is T3 directly activate the caspases or induce the release of cyt c? Author's response: According to what is reported in (Idriss et al., Table 2), beta T3 can up-regulation of cytochrome c. The same was reported by (Zappe,K et al., Table 2): “γ-tocotrienol specifically promoted cytochrome c release from the mitochondria into the cytosol of HeLa cells”. Again, we emphasise that this paper is based on secondary data. Furthermore, the exact molecule/receptor that T3 acts via is unclear. Reviewer's comment: Conclusion: Note that the authors only focused on in vitro data. Kindly update the conclusion accordingly. Author's response: Thank you for highlighting this oversight. We have revised this. Additional references to support the response from authors: Mazevet M, Moulin M, Llach-Martinez A, Chargari C, Deutsch É, Gomez AM, Morel É. Complications of chemotherapy, a basic science update. La Presse Médicale. 2013 Sep 1;42(9):e352-61. Sarbaz M, Monazah FM, Eslami S, Kimiafar K, Baigi SF. Effect of mobile health interventions for side effects management in patients undergoing chemotherapy: A systematic review. Health Policy and Technology. 2022 Sep 11:100680. Marampon F, Ciccarelli C, Zani BM. Biological rationale for targeting MEK/ERK pathways in anti-cancer therapy and to potentiate tumour responses to radiation. International journal of molecular sciences. 2019 May 23;20(10):2530. Zhou Y, Zhou B, Pache L, et al.: Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 2019; 10(1): 1–10 Bruford, E.A., Braschi, B., Denny, P., Jones, T.E., Seal, R.L. and Tweedie, S., 2020. Guidelines for human gene nomenclature. Nature genetics, 52(8), pp.754-758."
}
]
},
{
"id": "198198",
"date": "30 Aug 2023",
"name": "Gloria López",
"expertise": [
"Reviewer Expertise Drug discovery and development"
],
"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 well known that cancer is one of the main causes of death worldwide and it is a challenge to find adequate therapies for its treatment. Several natural compounds such as phytochemicals and vitamins have emerged as promising anticancer agents. The present review article reported by Mohamedahmed et al. focuses on the anticancer properties of tocotrienols, a component of the naturally occurring phytochemical Vitamin E.\nThe authors performed a systematized analysis of the publications reporting the anticancer activity of tocotrienols in all types of human cancer cell lines, to provide valuable insights into the molecular mechanisms underlying its antiproliferative action. From the analyzed data, the authors highlight that tocotrienols regulate several biomarkers that induce apoptosis and inhibition of proliferation, angiogenesis, and metastasis.\nThe information gathered here provides a starting point for more specific future studies to fully dissect the pathways by which tocotrienols exert their action. This is a fundamental step in bringing these natural products with promising antitumor activity to the clinic.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Yes\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? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-402
|
https://f1000research.com/articles/13-929/v1
|
15 Aug 24
|
{
"type": "Research Article",
"title": "Exploring the nexus between small-scale irrigation and household food security: A comprehensive study in Raya Kobo woreda, Amhara regional state, Ethiopia",
"authors": [
"Moges Asmare Sisay",
"Mohammed Yimam Ali",
"Addisu Belay",
"Mohammed Yimam Ali",
"Addisu Belay"
],
"abstract": "Background Food security’s multidimensional nature poses challenges in measurement and policy targeting. This comprehensive study explores the nexus between small-scale irrigation and household food security in Raya Kobo Woreda, Ethiopia, in a cross-sectional data.\n\nMethods Employing a two-stage sampling technique, the research examines 152 irrigation participants and 196 non-participants. Utilizing descriptive and econometric models, including a binary logit model and propensity score matching.\n\nResults The study reveals that 15% of participants and 12% of non-participants are food secure. Descriptive analysis reveals positive correlations between irrigation participation and household food security, dietary diversity, and food consumption scores. Econometric analysis identifies factors influencing participation, such as the age of the household head, family size and tropical livestock units have negative relationship with irrigation participation while the importance of agriculture is found to be positively associated with irrigation participation. Propensity score matching reveals a substantial positive impact on household expenditure, reaffirmed through sensitivity analysis.\n\nConclusion The findings contribute to understanding the complexities of small-scale irrigation in enhancing rural livelihoods and emphasize the importance of targeted interventions for sustained positive outcomes.",
"keywords": [
"Small-scale Irrigation",
"Food Security",
"Participation",
"Econometric Assessment"
],
"content": "1. Introduction\n\nIn the global context, recognizing food security as a fundamental human right (Benson, 2014a), Africa contends with widespread food insecurity affecting approximately thirty million people due to various factors (Benson, 2014b). With a significant proportion of the world’s poor residing in Africa South of the Sahara (Pangaribowo et al. 2013), food insecurity poses a critical challenge in the development agenda. Sub-Saharan Africa grapples with complex issues, including rapid population growth, unsustainable farmland management, recurring droughts, soaring food prices, political instability, and conflicts (FAO, 2015a; Habyarimana, 2015). Ethiopia, dealing with poverty and a substantial rural population reliant on rain-fed agriculture, views irrigation as a solution to enhance productivity, particularly in the water-abundant Amhara region (CoSAERAR, 2002a).\n\nDespite interventions, regions like Raya Kobo woreda in Ethiopia still confront food insecurity challenges despite having vast untapped irrigation potential. This study aims to assess the impacts of small-scale irrigation on household food security in Raya Kobo woreda, addressing crucial questions about factors influencing irrigation participation and the resulting impact on food security. In a country where agriculture significantly contributes to GDP, understanding these dynamics becomes pivotal for informed development strategies. The study’s significance lies in its potential to guide research, extension efforts, and policy making, fostering increased productivity and income while focusing on the assessment of small-scale irrigation’s impact on household food security in Raya Kobo woreda. This research aims to offer insights applicable to regions sharing similar physical and socioeconomic settings. The findings, therefore, carry broader implications for areas facing analogous challenges and possessing comparable potential for irrigation development. By concentrating on the specific context of Raya Kobo woreda, the research ensures a nuanced understanding of the intricate relationship between small-scale irrigation and food security.\n\nThe unique contribution of this study lies in its comprehensive assessment of the challenges and potential related to small-scale irrigation in Raya Kobo Woreda. Understanding the factors that hinder or facilitate irrigation adoption in this region, as well as evaluating the subsequent effects on food security, provides valuable knowledge for developing targeted interventions and policies.\n\nIn essence, the study seeks to answer questions such as: What are the specific challenges faced by Raya Kobo Woreda in utilizing its irrigation potential? How does small-scale irrigation contribute to or hinder household food security in this context? By delving into these questions within the specific socio-economic and physical settings of Raya Kobo Woreda, the research aims to offer insights that can inform not only local strategies but also serve as a reference for regions with similar challenges and potentials for irrigation development.\n\nThe transferability of these results to similar settings enriches the broader discourse on sustainable agricultural practices and interventions to alleviate food insecurity, fostering a more holistic and universally relevant approach to address this global concerned household food security.\n\n\n2. Literature review\n\nIn Ethiopia, where agriculture, particularly cereals, dominates the GDP, the multifaceted concept of food security is crucial. It encompasses physical and economic access to sufficient, safe, and nutritious food for an active and healthy life, with elements such as availability, accessibility, utilization, and stability. Understanding this complex nature is vital for formulating effective policies and interventions (Ram, 1996).\n\nFood security’s multidimensional nature poses challenges in measurement and policy targeting (FAO, 2015b). This section navigates through various indicators, including food availability, expenditure, access, and composite indexes. Emphasizing the demand-side approach, the focus is placed on parameters such as income, consumption, nutrition, and diet diversity (FAO, 2015c), providing a holistic framework for evaluating the impact of small-scale irrigation on rural household food security.\n\nWater’s pivotal role in agriculture makes irrigation a linchpin for food. This section classifies irrigation into small-scale, medium-scale, and large-scale categories. It zeroes in on small-scale, community-based groundwater irrigation, its significance in agricultural production, and its control and management by users, highlighting the central role of community involvement in decision-making processes (CoSAERAR, 2002b).\n\nInvestments in irrigation prove instrumental in fostering crop diversification, encouraging the use of modern inputs, and achieving higher yields (CoSAERAR, 2002). Small-scale irrigation, accorded priority in Ethiopia, emerges as a key player in ensuring food security by enhancing agricultural productivity and resilience. Studies include Bhattarai et al. (2007), highlighting how irrigation investments in India led to increased crop diversification and the adoption of chemical inputs. Similarly, Huang et al. (2006) demonstrated in China that irrigation facilitated a shift from low-value subsistence production to high-value market-oriented agriculture. Von Braun (2009) emphasized the role of irrigation in breaking the vicious circle of poverty and environmental degradation in areas with persistent rural poverty.\n\nIn the Ethiopian context, small-scale irrigation schemes are recognized as a policy priority for rural poverty alleviation and food security (Tesfaye et al., 2008). Eshetu et al. (2010) and Fikade (2020) documented the significant role of irrigation in Ethiopia, indicating increased income, resilience, and crop diversification. Hagos et al. (2009) further highlighted how irrigation in Ethiopia contributed to higher yields, income, consumption, and overall food security. The studies conducted by Watto & Mugera (2014) on groundwater markets in Punjab, Pakistan, aim to assess whether these markets enhance water use efficiency. The research explores the belief that water markets improve water productivity by efficiently transferring water to users for the highest marginal returns, leading to increased water efficiency among participants in groundwater markets. In the Pakistani context, informal groundwater markets offer an additional advantage, particularly benefiting resource-poor farmers facing financial constraints, as they cannot invest in wells. This perspective aligns with the broader discussion on the impacts of excessive irrigation on resource use sustainability and water use efficiency.\n\nFeng Ye et al. (2023) eexamines the impact of rural industrial integration on agricultural total factor productivity (ATFP) in China, emphasizing heterogeneity and spatial spillover effects. Findings indicate a positive correlation between rural industrial integration and ATFP growth, driven by technological advancements and efficiency improvements. Regional differences exist, with the western region experiencing the most significant impact. While the study suggests a marginal incremental effect in areas with higher ATFP, a negative spatial spillover effect is observed, implying a potential inhibition of ATFP growth in surrounding regions. Relating this to excessive irrigation, the study underscores the complex interplay between agricultural practices, industrial integration, and regional dynamics, emphasizing the need for nuanced approaches to enhance resource sustainability and water use efficiency.\n\nIrrigation methods play a pivotal role in shaping the sustainability and productivity of smallholder farming, impacting resource utilization and overall agricultural practices. The two primary categories, surface irrigation and sub-surface irrigation, are employed based on factors such as water resources, topography, and crop types, influencing the delivery of water to fields.\n\nSurface irrigation encompasses several methods, each tailored to specific conditions. Basin irrigation, the most common, involves creating enclosed land sections for water retention, suitable for all soil types but with a high initial cost (Fikade, 2020). Furrow irrigation, utilizing channels along the field’s slope, provides uniform water application but demands substantial labor and investment (Dupriez & De Leener, 2002). Border irrigation extends basin principles to sloping fields, emphasizing efficient water use but requiring uniform land grading and supervision. Flood irrigation, an ancient method, is cost-effective but inefficient, resulting in water wastage due to runoff and evaporation.\n\nInnovative techniques like drip irrigation and solar-powered irrigation revolutionize water use efficiency, particularly in arid regions. Drip irrigation, delivering water directly to crop roots through pipes, minimizes evaporation, conserves water, and enhances yields significantly (Dupriez & De Leener, 2002).\n\nSolar-powered irrigation, harnessing solar energy to pump and distribute water, addresses the energy costs associated with traditional methods, contributing to sustainability. Solar-powered irrigation systems (SPIS) offer significant advantages, providing a reliable energy source for water pumping in remote areas without grid access. This proves crucial in regions facing economic water scarcity, helping mitigate drought effects and enhancing year-round cultivation. SPIS contribute to increased yields, diversification, improved food security, and income generation for small-scale farmers. Despite their benefits, SPIS adoption faces challenges such as high initial costs, requiring innovative financing and technical expertise. Unregulated use may lead to unsustainable water practices and over-abstraction of groundwater. On a national scale, SPIS contribute to rural development, reduce dependence on fossil fuels, and play a role in climate change mitigation by replacing traditional power sources with renewable energy. Addressing challenges requires comprehensive water accounting, smart management, and visionary policies (FAO, 2018).\n\nAnother noteworthy approach is sprinkler irrigation, simulating rainfall by spraying water into the air. While ensuring uniform water distribution and efficient use, sprinkler systems come with higher initial costs and maintenance requirements (Dupriez & De Leener, 2002). This is offset by their ability to control water application rates and provide temperature-related benefits like cooling crops and frost control during freezing temperatures. These diverse irrigation techniques underscore the intricate choices faced by smallholder farmers, highlighting the need for sustainable and efficient practices (FAO, 2018).\n\nAmar Razzaq et al. (2022) study on the impact of participation in the groundwater market on farmland, income, and water access in Pakistan, identify positive effects of water markets on farmers’ income and equity. However, the research concurrently raises concerns regarding the overextraction of groundwater and inefficiencies in water resource utilization. The study highlights the absence of inherent mechanisms to control overuse in the current water market system, noting that some tube well owners operate with lower efficiency, indicating challenges associated with excessive irrigation. The conclusion stresses the urgent need for policy options to improve water use efficiency, safeguard groundwater sustainability, and ensure farmers’ incomes and food security. While recognizing the Punjab Water Act of 2019 as a positive step, the study raises questions about its implementation, particularly regarding tube well licensing and abstraction. The researchers recommend promoting participatory irrigation management to jointly control overexploitation and formulate regulations to enhance groundwater irrigation efficiency for the overall welfare of the community.\n\nDespite Ethiopia’s rich historical legacy in irrigation, challenges such as fragmented farmland, political instability, and financial constraints have impeded its comprehensive development (CoSAERAR, 2002b). An exploration of these challenges provides context to the intricate landscape of irrigation initiatives in the country.\n\nEthiopia grapples with food security challenges stemming from population growth, deforestation, and land distribution issues (World Bank, 2013a). Acknowledging small-scale irrigation as a pivotal solution underscores the government’s commitment to addressing these challenges and ensuring sustainable food security in the country (World Bank, 2013b).\n\nA plethora of empirical studies has delved into the intricate web of factors influencing household participation in irrigation and the ensuing impact on food security. Education, gender dynamics, landholding patterns, access to credit, farm size, livestock ownership, and the adoption of modern technologies have surfaced as pivotal elements shaping participation trends and determining the overall food security scenario (Smith et al., 2017; Zerihun et al., 2020).\n\nThe realm of irrigation techniques spans from traditional surface methods to advanced systems like drip and sprinkler irrigation, each wielding a distinct influence on water use efficiency and crop yield (Kumar and Singh, 2015; Khan et al., 2019). This section provides nuanced insights into the advantages and disadvantages associated with various methods, enriching the understanding of the diverse landscape of irrigation practices and their implications for agricultural productivity.\n\n\n3. Methods\n\nRaya Kobo Woreda, nestled in the Amhara National Regional State, Ethiopia, serves as the canvas for this study. Geographically diverse and economically dynamic, it covers an expanse from 11°51′45.63′′ to 12°19′24.97′′ N north latitude and 39°19′54.87′′ to 39°53′2.33′′ E longitude. With altitudes ranging from 1360 to 3000 meters, the agro-ecological zones exhibit a fascinating blend of 59% kola, 3% Dega, and 38% woynadega. Climate intricacies, population demographics, and economic activities weave a tapestry crucial for understanding the nexus between small-scale irrigation and household food security.\n\nFor a comprehensive understanding, both quantitative and qualitative data were harnessed from primary and secondary sources. Primary data, gleaned from sample farmers in Raya Kobo Woreda’s key kebeles, Aradum, Ayub, and Abuare, provides an on-the-ground perspective. Semi-structured questionnaires, thoughtfully designed, unravel economic and social factors shaping households. Secondary data, a qualitative treasure trove, emerges from local offices, governmental organizations, publications, and policy documents.\n\nThe study utilized a multi-stage sampling methodology to derive a representative sample from the population frame. In the initial phase, a study Woreda was purposefully selected, leveraging the researcher’s familiarity and the widespread implementation of modern small-scale irrigation projects. Subsequently, three specific irrigation sites (Aradum, Ayub, and Abuarie) were purposively chosen from the 43 rural kebeles within the study Woreda. The selection criteria included factors such as accessibility, proximity to the study Woreda, and the potential number of beneficiaries of irrigation projects. The sample size (n=348) was determined utilizing Yamane’s formula, ensuring a 95% confidence level and a 5% margin of error (Yamane, 1967).\n\nTo establish the sample frame, the Water User Association members’ registry was employed for household selection, with Key Interview informants and Focus Group Discussion members identified through purposive sampling. In the final sampling stage, a simple random sampling approach, employing the probability proportionate to size (PPS) random sampling technique, was implemented to assure the representativeness of the population.\n\nTable 1 illustrates the population and sample size distribution across different kebeles. The total population of the study area was determined to be 2701, as provided by the Raya Kobo Woreda Agricultural Office. Sample sizes for each kebele were calculated using proportional allocation, ensuring equitable representation across both beneficiary and non-beneficiary groups. The table comprehensively presents the total population, participant sample, and non-participant sample for each kebele, offering a transparent overview of the distribution strategy employed in the study.\n\n3.4.1 Descriptive statistics\n\nDescriptive statistics, including mean, standard deviation, and graphical representations, are employed to illustrate the socioeconomic, demographic, and institutional characteristics of the sampled households. The evaluation of household food security utilizes methodologies such as the Household Food Insecurity Access Scale (HFIAS), Household Dietary Diversity Score (HDDS), and Food Consumption Score (FCS) to offer a detailed understanding of food security conditions.\n\n3.4.2 Econometric models\n\nEconometric analysis, specifically logit regression, addresses factors influencing participation in small-scale irrigation. Propensity Score Matching (PSM) is employed to assess the impact of irrigation participation on productivity and income. The PSM model considers conditional independence assumption (CIA) and common support condition (CSC) to mitigate selection bias in observational studies and quasi-experimental evaluations. These econometric models contribute to a robust analytical framework for understanding the determinants and consequences of small-scale irrigation participation, crucial for formulating effective agricultural policies.\n\nThis study, titled “Exploring the Nexus between Small-Scale Irrigation and Household Food Security: A Comprehensive Study in Raya Kobo Woreda, Amhara Regional State, Ethiopia,” involved human participants and adhered to strict ethical guidelines. Informed consent was obtained from all participants after providing them with detailed information about the study, ensuring their right to withdraw at any time. Participant confidentiality and anonymity were rigorously maintained, with personal identifiers anonymized and data securely stored.\n\nThe study received approval from the Institutional Review Board (IRB) committee of the Faculty of Business and Economics at Woldia University on July 13, 2023 (Ref: FBE/RCSTT/216/2023). Field research was conducted respectfully, considering the cultural and social context of the Raya Kobo Woreda, and aimed to benefit the community by enhancing understanding of food security and asset-building strategies.\n\n\n4. Result and discussion\n\n4.1.1 Descriptive statistics of categorical variables\n\nInvolving 348 surveyed households, 43.68% participated in small-scale irrigation, revealing significant differences between participants and non-participants. Gender-wise, 67.10% of participants were male-headed households, highlighting a strong association between gender and participation. Access to improved agricultural technology was pivotal, with 67.10% of participants having access, in contrast to 28.57% among non-participants. This disparity underscored the positive influence of technology access on irrigation participation. Notably, 57.5% of participant households received extension services, compared to 41.83% among non-participants, indicating a substantial divergence in service contact.\n\n4.1.2 Descriptive statistics of continuous variables\n\nExploring demographic and socio-economic factors revealed significant differences. The average age of household heads was 51 years, with a notable mean difference between participants (42.34 years) and non-participants (57.77 years), suggesting that younger household heads were more likely to engage in small-scale irrigation. Livestock ownership, measured in Tropical Livestock Units (TLU), displayed a mean difference between participants and non-participants, indicating diverse livestock sizes.\n\n4.1.3 Food security status of sample households\n\nTable 2 shows that the assessment of household food security using the Household Food Insecurity Access Scale (HFIAS) revealed 63.51% of households were food secure, while 36.49% were food insecure. Among irrigation users, 71.71% were food secure, underscoring a significant positive correlation between participation in small-scale irrigation and household food security. Pearson correlation confirmed that participants were more food secure than non-participants, highlighting the potential positive impact of irrigation on food security.\n\n** Means significant at 5% level of significance.\n\n4.1.4 Household Dietary Diversity Score (HDDS)\n\nThe Household Dietary Diversity Score (HDDS) for the previous 24 hours in this study showed that 7.18% of households consumed 1 to 3 food groups (low diversity), 31.61% consumed 4 to 5 food groups (medium diversity), and 61.21% consumed more than 5 food groups (high diversity), based on HDDS thresholds. The data revealed that about 69.74% of irrigation user households and 54.59% of non-user households had a high dietary diversity of 6 or more food groups. Additionally, 24.34% of irrigation users and 37.24% of non-users had a medium dietary diversity of 4 to 5 food groups. Low dietary diversity of less than 3 food groups was observed in only 5.92% of irrigation users and 8.16% of non-users (Table 3). The average dietary diversity score for the study area was 6.37. Notably, irrigation user households had a higher mean dietary diversity score of 7.11 compared to 5.79 for non-irrigating households. This difference in mean diversity scores between irrigation users and non-users was statistically significant at the 5% significance level, indicating that irrigating households consumed a more diverse range of food groups than non-irrigating households.\n\n** Means significant at 5% level of significance.\n\n4.1.5 Household Food Consumption Score (HFCS)\n\nThe Household Food Consumption Score (HFCS) is derived from the Household Dietary Diversity Score (HDDS) by incorporating frequency-weighted data on the consumption of eight distinct food groups: main staples, pulses, vegetables, fruits, meat and fish, milk, sugar, and oil. The HFCS is calculated based on the frequency of consumption of these food groups over a standard 7 day period, with each group assigned a specific weight. The weighted scores are then summed to obtain the HFCS, which is subsequently categorized into food consumption groups using predefined thresholds: 0-28 (food poor), 28.5-42 (borderline), and above 42 (acceptable) according to guidelines from the World Food Programme (WFP) and the International Food Policy Research Institute (IFPRI). The results, as shown in Table 4, indicate that 73% of irrigation users exhibited acceptable food consumption, with 25% classified as borderline and 1.97% with poor food consumption scores. For non-irrigation users, 61.22% had acceptable food consumption, 33.16% were borderline and 5.61% were classified as poor. Overall, the study revealed that 66.38% of households in the area had acceptable food consumption scores, while only 4.02% exhibited poor food consumption. These findings provide insights into the food security status of households, emphasizing the importance of irrigation in enhancing food consumption adequacy.\n\n** Means significant at 5% level of significance.\n\n4.1.6 Challenges in implementing small-scale irrigation\n\nEmbarking on the path of implementing small-scale irrigation practices in the study area reveals a nuanced journey marked by economic and environmental challenges. These challenges not only mirror broader issues in regional irrigation development but also shed light on critical hurdles hindering the full realization of the potential benefits for rural households.\n\nWhile small-scale irrigation holds promise in boosting rural incomes, the survey uncovers key constraints that demand immediate attention. Financial considerations, insufficient irrigation water supply, flaws in marketing systems, limited access to inputs and facilities, and persistent threats from pests and diseases collectively cast a shadow on the effectiveness of small-scale irrigation.\n\nTable 5 provides a snapshot of specific challenges faced by participants in small-scale irrigation, offering a deeper understanding. A noteworthy 30.17% of respondents highlight water scarcity as a predominant issue. Additionally, concerns about administrative hurdles, the absence of an efficient marketing system, pests and diseases, suboptimal productivity in existing schemes, and a lack of awareness about irrigation water management make up 11.78%, 23.85%, 14.08%, 7.75%, and 12.36%, respectively.\n\nThese findings underscore the intricate web of challenges associated with small-scale irrigation, emphasizing the need for holistic strategies and interventions. Addressing these constraints is imperative for the sustainable and impactful implementation of small-scale irrigation practices in the region, ensuring enduring success amid the evolving landscape.\n\n4.1.7 Financial landscape: Revealing household expenditure dynamics\n\nDelving into the economic tapestry of households, the annual total expenditure per adult equivalent emerges as a pivotal metric, encapsulating both food and non-food expenditures. This financial gauge serves as the lifeline for households, ensuring the fulfillment of essential calorie intake per adult equivalent daily and meeting other fundamental needs. A robust income source empowers households to secure the required daily food intake. The total annual expenditure is underpinned by income streams stemming from diverse channels, including farm and non-farm activities like livestock and crop production, petty trade, employment, and the sale of natural products.\n\nThe comparative analysis of annual total expenditures for irrigation participants and non-participants unfolds intriguing insights. Table 6 shows the mean annual expenditure for irrigation participants stands at 12,096.85 ETB per adult equivalent, surpassing its non-participant counterpart at 9,069.73 ETB. This observed difference undergoes statistical scrutiny through a t-test, revealing its significance at the 1% level. The financial terrain, thus, underscores the noteworthy impact of small-scale irrigation participation on household expenditure patterns, portraying a compelling narrative of economic dynamics in the study area.\n\n*** Means significant at 10% level of significance.\n\nEmbarking on the econometric voyage, our vessel charts a course through the intricate waters of model specifications and post-estimation tests. The earlier glimpses into descriptive statistics hinted at the prosperity of treatment households engaged in small-scale irrigation. However, for a more profound understanding, we now delve into a rigorous exploration in three acts: delineating model specifications and post-estimation tests, unveiling logit regression results for the treatment-dependent variable, and illuminating the results and discussions of propensity score matching for the outcome variable.\n\n4.2.1 Setting the stage: Model specifications and tests\n\nBefore the variables join the model’s ensemble, rigorous tests ensure the model’s integrity. The journey begins with a scrutiny of multicollinearity, dispelling any whispers of interrelated explanatory variables. The variance inflation factor (VIF) stands as the sentinel, ensuring values remain below 10. Contingency coefficients, guardians against association problems, assure a harmonious relationship among dichotomous variables. Heteroskedasticity faces the Brush Pagan test, with results negating its presence. The model emerges fortified, with its foundations unshaken by specification violations.\n\n4.2.2 Figuring out determinants: Logit regression quest\n\nEmbarking on small-scale irrigation implementation in our study area unveils a narrative entwined with economic potential and environmental complexities. These challenges, reflecting broader issues in regional irrigation, illuminate critical hurdles hindering the realization of benefits for rural households.\n\nWhile small-scale irrigation holds promise for rural income upliftment, our survey spotlights immediate constraints. From financial considerations to water scarcity, marketing system glitches, limited inputs access, and persistent pests and diseases, these challenges collectively overshadow small-scale irrigation effectiveness.\n\nThese findings emphasize the need for scholarly interventions. Addressing these constraints is imperative for the sustainable success of small-scale irrigation practices in our region, firmly anchoring them in the evolving landscape of agricultural development.\n\n4.2.3 Unveiling agricultural realities: What logit regression reveals\n\nThe logistic regression analysis in Table 7, examining factors influencing a binary outcome related to households (hhp), offers valuable insights into various predictors. Age of the household head (agehh) emerges as a significant factor, with a one-unit increase associated with a statistically significant decrease of approximately 0.39 in the log-odds of the binary outcome. Conversely, the gender of the household head (sexhh) and education level (edushh) do not exhibit statistically significant associations with the log-odds, as their respective p-values exceed 0.05. Family size (famsize) shows a marginally significant negative association, indicating that an increase in family size is associated with a decrease of approximately 0.51 in the log-odds of the binary outcome. Livestock units (tlu) exhibit a statistically significant negative association, implying that a one-unit increase in livestock units corresponds to a decrease of approximately 0.21 in the log-odds. The type of land ownership or use (culland), involvement in the workforce (actforce), and credit access (crdtacc) do not display statistically significant associations with the binary outcome.\n\nAdditionally, the extention service (exstenserv) shows a statistically significant negative association, suggesting that a one-unit increase is associated with a decrease of approximately 1.40 in the log-odds. The statistically significant negative association between extension service contacts (exstenserv) and irrigation participation in the logit model results suggests that, on average, an increase in extension service contacts is associated with a decrease in the likelihood of participating in irrigation. This unexpected finding prompts consideration of potential interpretations. One plausible explanation could be that the current structure or content of existing agricultural extension programs may not effectively address or promote irrigation practices among the targeted population. The negative coefficient may indicate that, despite engaging with extension services, farmers may not be receiving adequate guidance, information, or support related to irrigation methods or may encounter challenges that hinder their participation.\n\nThe importance of agriculture (impagri) exhibits a significant positive association, indicating that a one-unit increase leads to an increase of approximately 3.97 in the log-odds. Remittances received by the household (remitance) do not demonstrate a statistically significant association with the log-odds. The intercept term (-cons) represents the log-odds when all other predictor variables are zero, with a large positive value contributing significantly to the overall prediction of the binary outcome. The LR chi2, Prob > chi2, Log likelihood, and Pseudo R2 values collectively provide information on the model’s goodness of fit, while the statistically significant coefficients and associated p-values aid in evaluating the individual predictors’ significance in explaining the variation in the binary outcome.\n\n4.2.4 Unveiling impact: Propensity score matching in small-scale irrigation analysis\n\nIn this section, we delve into the impact analysis of the study, providing an intricate exploration of the process employed to discern the program’s influence through the lens of the propensity score matching model. The journey encompasses the meticulous estimation of propensity scores, identification of the common support region, selection of matching algorithms, conducting balancing tests, and ultimately, calculating the treatment effect.\n\n4.2.5 Estimation of propensity score: Navigating probabilities in irrigation practices\n\nTo address the study’s second objective evaluating the impact of small-scale irrigation on household total expenditure per adult equivalent we employed propensity score matching (PSM). This versatile model, hinging on binary variables and predictors, was constructed using a logit regression. The logit regression was chosen for its commonality in propensity score estimation. The process involved considering a myriad of observable characteristics to construct propensity scores, ensuring their exhaustiveness. However, particular attention was paid to exclude characteristics influenced by the treatment, such as household income, from the covariates in the propensity score estimation. The results revealed significant influences of four explanatory variables on small-scale irrigation practices.\n\n4.2.6 Common support condition: Navigating the overlapping realms\n\nThe subsequent step in the propensity score matching technique is the establishment of the common support condition. This ensures that only observations within the common support region are considered for matching, while others are excluded from further analysis. The kernel density in Figure 1, estimate visually displayed the distribution of total sample households, highlighting the common support region. The participants predominantly occupied the right side, with non-participants concentrated on the left. This broad area of similarity in propensity scores between treated and control groups are aptly termed the common support region, forming the foundation for subsequent impact assessments.\n\n4.2.7 Harmonizing realms: Crafting common grounds through propensity score matching\n\nThe final task involves discarding observations falling outside the common support region, refining the match. Table 8 displays the outcomes, with overall estimated propensity scores ranging from 0.006504 to 0.980515, encapsulating the common support essence. Among participants, scores ranged from 0.010272 to 0.980515, and for non-participants, from 0.006504 to 0.91518. Calibration excludes 16 outliers, bidding adieu to the analysis due to scores beyond common support boundaries.\n\nWith 332 resilient households within this realm, the stage is set to predict the impact of small-scale irrigation on annual total expenditure per adult equivalent. The average propensity score, dancing at approximately 0.436782, unveils a narrative of probability. On average, the probability of participation stands at about 0.637321 for sampled households, while non-participants echo a probability of 0.281261. In this statistical symphony, common threads are woven, laying the foundation for a robust impact prediction.\n\nFigure 2 depicts the distributions of propensity scores and the common support region. The lower halves of the histogram display the propensity score distribution of non-participants in small-scale irrigation, while the upper halves showcase the propensity score distribution of small-scale irrigation participant households. The red-colored (Untreated on support) and green-colored (Treated on support) sections indicate observations in the non-participant group and participant group, respectively, that have suitable comparisons. On the other hand, the orange-colored (Treated off support) and blue-colored (Untreated-off support) segments represent observations in the small-scale irrigation participant and non-participant groups that lack a suitable comparison, with their propensity score values approaching one and zero, respectively. This visualization helps illustrate the overlap and common support region essential for an effective propensity score matching analysis.\n\n4.2.8 Precision in propensity: Orchestrating impact with kernel matching\n\nIn the realm of propensity score matching, where precision is paramount, the art lies in selecting the right algorithm. A comprehensive evaluation of nearest neighbor, radius matching, and kernel matching unfolds, scrutinizing their efficacy under varied scenarios. Among these, kernel matching emerges as the virtuoso, harmonizing precision and information richness.\n\nAs the statistical orchestra’s conductor, the kernel matching algorithm, adorned with a calibrated caliper, takes center stage. Bestowing each treated individual with a weight of one maximizes precision, ensuring a symmetrical impact evaluation. As shown in Table 9 the spotlight then shifts to the Treatment Effect on the Treated (ATT), reaching a crescendo in the analysis. Findings resonate with significance at the 1% probability level, highlighting the transformative influence of small-scale irrigation on household expenditure a substantial 20.85% surge, totaling 2557.74 ETB annually.\n\nIn the meticulous dance of controlling pre-intervention disparities, the study unfolds a narrative of positive and statistically significant divergence between participant and non-participant households. This echoes the impactful strides observed in the Panganai irrigation scheme in Bikita district, Zimbabwe, as explored by Bernard Chazovachii in 2012. This study, akin to a well-conducted symphony, underscores the pivotal role of small-scale irrigation in orchestrating prosperity and resilience in rural landscapes.\n\nTable 9 presents a comparison of total expenditure per adult equivalent (AE) between the treated group (those participating in small-scale irrigation) and the control group (non-participants). The unmatched figures indicate that the total expenditure per AE for the treated group is 12,096.85, while for the control group, it is 9,069.73, resulting in a difference of 3,027.12. The standard error (S.E.) associated with this difference is 343.26, and the t-test value is 8.82, indicating a statistically significant difference between the two groups.\n\nIn the case of the average treatment effect on the treated (ATT), the total expenditure per AE for the treated group is 12,266.28, and for the control group, it is 9,708.54. The calculated difference is 2,557.74, with a standard error of 446.65 and a t-test value of 5.73. This signifies a statistically significant positive impact of small-scale irrigation participation on household expenditure, reinforcing the economic benefits observed in the propensity score matching analysis. The results suggest that households engaged in small-scale irrigation exhibit higher total expenditures compared to their non-participant counterpart.\n\n4.2.9 Harmony in equivalence: A ballet of covariate balance\n\nIn the delicate choreography of impact evaluation, achieving balance is akin to a ballet, where the matched units in treatment and comparison groups pirouette in statistical harmony. The litmus test for this synchronization lies in the t-test, a discerning maestro in determining if the means of covariates, included in the propensity score, orchestrate a statistically comparable performance.\n\nAs the curtains rise on the stage of statistical scrutiny, the t-test takes center stage, its preference evident when the gaze is set on the statistical significance of results. Solivas, Ramirez, and Manalo (2007) set the rhythm, guiding the evaluator through this symphony of equivalence. The results unfurl like a seamless ballet, revealing that the constructed treatment and comparison groups dance to the same statistical tune.\n\nThe absence of significant difference, as revealed by the t-test, paints a portrait of covariate balance. The narrative woven through this statistical ballet is one of satisfaction wherein the covariate balance criteria stand fulfilled. In this elegantly orchestrated dance of statistical equivalence, the study establishes a foundation of trust in the comparability of treatment and comparison groups, ensuring that the impact analysis unfolds on a stage set with the backdrop of balance.\n\n\n5. Conclusions and recommendations\n\nThis study, situated in Raya Kobo Woreda within the North Wollo Zone of the Amhara Regional State, aimed to comprehensively evaluate the influence of small-scale irrigation practices on the annual expenditures of households, encompassing both food and non-food aspects. The research design involved the collection of cross-sectional data in 2022, where 348 farmers were selected through a multistage stratified random sampling approach. Among this sample, 152 households actively participated in small-scale irrigation, while the remaining 196 did not engage in such practices. The analytical framework incorporated descriptive statistics, econometric methods, and propensity score matching to derive meaningful insights from the collected data.\n\nThe primary data, acquired through interviews, underwent rigorous statistical analysis, employing measures such as mean, standard deviation, percentage, T-test, chi-square test, and t-test. The study particularly focused on food security, revealing that 63.51% of households overall maintained food security, with noteworthy distinctions observed between irrigation participants (71.71% food secure) and non-participants (57.14% food secure). The investigation also highlighted significant variations in diet diversity and food consumption scores between irrigators and non-irrigators.\n\nIdentified constraints in small-scale irrigation practices encompassed challenges such as water shortages, administrative issues, marketing problems, pests and diseases, and low scheme productivity. The logit model scrutinized eleven variables, ultimately pinpointing four significant factors negatively affecting irrigation practices: the age of the household head, extension service, TLU, and improved agricultural technologies.\n\nFurthermore, propensity score matching techniques were employed to assess the financial impact, revealing that small-scale irrigation participants annually spent 2557.74 ETB more than their non-participating counterparts, indicative of a positive influence on farm income. To ensure the robustness of these findings against hidden biases, average treatment effects were scrutinized using the Rosenbaum (2002) Bounding approach under varying gamma values in sensitivity analysis, affirming the resilience of the results against unobservable selection bias.\n\nTo promote sustainable small-scale irrigation practices and enhance food security, tailored recommendations proposed for policymakers, development practitioners, and farmers.\n\nPolicymakers are urged to prioritize investments in irrigation infrastructure, allocating substantial budgets for construction and maintenance. Additionally, enacting policies to address post-harvest challenges and formulating supportive regulations for small-scale irrigation practices are essential.\n\nFor development practitioners, the focus should be on enhancing extension services, conducting targeted capacity-building programs, and promoting collaborative initiatives among farmers. Specifically, increased engagement through workshops and field visits, specialized training programs for farmers, and facilitation of cooperative efforts recommended.\n\nFarmers are encouraged to actively participate in training programs, establish irrigation cooperatives to collectively address challenges, and adopt sustainable irrigation practices. This holistic approach ensures that each stakeholder group plays a vital role in fostering sustainable small-scale irrigation, contributing positively to farmers’ livelihoods and overall food security.\n\nThe study was approved by the Institutional Review Board (IRB) committee of the Faculty of Business and Economics at Woldia University on January 2, 2022 (Ref: FBE/RCSTT/189/2022). The principal researcher provided a written consent form for research participants to participate in the household survey, conforming to the research ethics guidelines of Woldia University.",
"appendix": "Data availability\n\nZenodo: Underlying data for ‘Exploring the nexus between small-scale irrigation and household food security: A comprehensive study in Raya Kobo Woreda, Amhara Regional State, Ethiopia’, https://zenodo.org/records/13141105.\n\nZenodo: The questionnaire that supports the findings of this research are available in the Zenodo: https://zenodo.org/records/13077465.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nBenson T: Revolutionizing agricultural practices for sustainable development: Explore the paradigm shift in agriculture towards sustainable development, uncovering innovative practices that hold the key to a resilient and eco-friendly future.2014a.\n\nBenson T: Smallholder empowerment: A path to food security: Delve into the transformative journey of smallholders, revealing how empowerment becomes a catalyst for ensuring food security, creating a ripple effect in local communities.2014b.\n\nBhattarai M, Barker R, Narayanamoorthy A: Who benefits from irrigation development in India? Implication of irrigation multipliers for irrigation financing. Irrigation and Drainage: The Journal of the International Commission on Irrigation and Drainage. 2007; 56(2-3): 207–225. Publisher Full Text\n\nChazovachii B: The impact of small scale irrigation schemes on rural livelihoods: The case of Panganai irrigation scheme Bikita District Zimbabwe. Journal of Sustainable Development in Africa. 2012; 14(4): 217–231.\n\nCoSAERAR: Empowering communities through agricultural initiatives: Witness the transformative power of agricultural initiatives in empowering communities, fostering a sense of ownership and sustainability that extends beyond the fields.2002a.\n\nCoSAERAR: Evaluating the impact of agricultural initiatives: Assess the transformative power of agricultural initiatives, gauging their impact on communities and ecosystems, and envisioning a future shaped by sustainable practices.2002b.\n\nDupriez H, De Leener P: Land use and life: Ways of water, Run off, irrigation and drainage. Tropical Handbook.2002.\n\nEshetu S, Belete B, Goshu D, et al.: Income diversification through improved irrigation in Ethiopia: Impacts, constraints and prospects for poverty reduction.2010.\n\nFAO: Advancements in sustainable agriculture: Explore the cutting-edge advancements propelling sustainable agriculture forward, providing a glimpse into a future where innovation and environmental consciousness converge.2015a.\n\nFAO: Enhancing agricultural resilience: A global perspective: Gain a global perspective on enhancing agricultural resilience, discovering strategies that fortify the industry against the challenges posed by a rapidly changing world.2015b.\n\nFAO: Small-scale irrigation for food security: Current perspectives: Dive into the world of small-scale irrigation, exploring current perspectives that highlight its pivotal role in ensuring food security on a local and global scale.2015c.\n\nFAO: The benefit and risks of solar-powered irrigation: A global overview ISBN-978-92-5-130479-2/FAO.2018.\n\nFikade GG: The contribution of small-scale irrigation on the livelihood of smallholder farmers: The case of Mereb-Leke Woreda, Central Tigray, Ethiopia (Doctoral dissertation, HU).2020.\n\nFeng Y, Shengz Q, Nimra N, et al.: Does rural industrial integration improve agricultural productivity for sustainable food production? Front. Sustain. Food Syst. 2023; 7: 1191024.\n\nHabyarimana B: Capacity-building for smallholder farmers: Uncover the transformative impact of capacity-building initiatives for smallholder farmers, paving the way for increased productivity and sustainable agricultural practices.2015.\n\nHagos F, Makombe G, Namara RE, et al.: Importance of irrigated agriculture to the Ethiopian.2009.\n\nHuang Q, Rozelle S, Lohmar B, et al.: Irrigation, agricultural performance and poverty reduction in China. Food Policy. 2006; 31(1): 30–52. Publisher Full Text\n\nKhan, et al.: Transforming agriculture: Challenges and opportunities: Navigate the challenges and opportunities shaping the transformation of agriculture, providing insights into the dynamic landscape of a crucial global industry.2019.\n\nKumar, Singh: Modernizing agricultural techniques: A global perspective: Explore the global perspective on modernizing agricultural techniques, envisioning a future where technology and innovation harmonize with traditional farming practices.2015.\n\nPangaribowo EH, Gerber N, Torero M: Food and nutrition security indicators: A review.2013.\n\nRam GS: Food security system, poverty issues and rural development. Agric. Econ. Res. Rev. 1996; 9(2): 121–127.\n\nRazzaq A, Xiao M, Zhou Y, et al.: Towards sustainable water use: Factors influencing farmers’ participation in the informal groundwater markets in Pakistan. Front. Environ. Sci. 2022; 10: 944156. Publisher Full Text\n\nRosenbaum PR: Attributing effects to treatment in matched observational studies. J. Am. Stat. Assoc. 2002; 97(457): 183–192. Publisher Full Text\n\nSmith MD, Rabbitt MP, Coleman-Jensen A: Who are the world’s food insecure? New evidence from the Food and Agriculture Organization’s food insecurity experience scale. World Dev. 2017; 93: 402–412. Publisher Full Text\n\nSolivas, Ramirez, Manalo: Empowering communities through agricultural initiatives: Witness the transformative power of agricultural initiatives in empowering communities, fostering a sense of ownership and sustainability that extends beyond the fields.2007.\n\nTesfaye A, Bogale A, Namara RE, et al.: The impact of small-scale irrigation on household food security: The case of Filtino and Godino irrigation schemes in Ethiopia. Irrig. Drain. Syst. 2008; 22: 145–158. Publisher Full Text\n\nVon Braun J: Overcoming the world food and agriculture crisis through policy change and science. Trust for Advancement of Agricultural Sciences (TAAS), Fourth Foundation Day Lecture. New Delhi.2009.\n\nWatto A, Mugera A: Does the risk of groundwater depletion drive tube-well technology adoption: A case of Pakistan.2014.\n\nWorld Bank: Global strategies for food security: Uncover global strategies for ensuring food security, exploring the multifaceted approaches that address the complex challenges of feeding a growing population.2013a.\n\nWorld Bank: Investing in agriculture: A global overview: Gain a global overview of the strategic importance of investing in agriculture, understanding how financial support can catalyze positive change in food systems worldwide.2013b.\n\nYamane T: Taro Yamane method for sample size calculation: The survey causes of mathematics anxiety among secondary school students in Minna Metropolis. Mathematical Association of Nigeria (MAN). 1967; 46(1): 188.\n\nZerihun, et al.: Innovations in agricultural practices: A case study: Uncover transformative innovations in agricultural practices through a captivating case study, offering a glimpse into the future of sustainable and efficient farming methodologies.2020."
}
|
[
{
"id": "318977",
"date": "20 Sep 2024",
"name": "Yismaw Ayelign Mengistu",
"expertise": [
"Reviewer Expertise livelihood diversification and food security",
"taxation",
"industrial performance and innovation",
"urbanization and development",
"international finance and macroeconomic performance",
"any other development economics issues."
],
"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 authors raised critical issue from both policy and academic perspective, i.e. rural food security. Food security is one of the targets of SDG2 which aims to end hunger in its all forms and everywhere.\n\nOf course, food security remained pervasive in the Ethiopian context as reports reveal that 21.1% in total household are under severe food insecure [ ref 1 ] and 52.1% of households face moderate or severe food insecurity [ ref 2 ]. One of the intervention mechanisms to relieve such chronic problems is enhancing agricultural productivity through small scale irrigation. NB: the Ethiopian land tenure is dominated by small scale land possession which requires intensive farming.\n\nI appreciate the authors’ intention and effort to contribute to such important topic. Specific comments Methodologically:\nThe authors employed propensity score matching estimation technique to get the food security impact of small-scale irrigation participation. The sample size allocation between participants (152) and non-participants (196) is nice because the control group (non-participants in this case) is required to be larger in order to get better propensity of matching. It is clear, however, that adoption of small-scale irrigation as agricultural technology which increases land productivity is constrained by the availability and accessibility of water supply to plots of land. The natural position of plot of land for some households allows them to adopt but because of distance from irrigation scheme and/or steepness of land, for other households it becomes difficult or costly to adopt. This affects the ability to adopt even if farm households have the willingness to so. Given that farm households are rational producers and adoption of irrigation provides positive economic incentive, those who are able to adopt (because their land is closer or suitable to get irrigation access) will adopt which may cause selection bias, i.e. the adoption decision is not made on random basis but rather because of observable factor that influences the adoption decision of farm households. I suggest, if the authors’ applied estimation technique which addresses the endogeneity issue particularly caused by selection bias. For instance, endogenous switching regression might help. It would be good if the authors utilized longitudinal dataset in order to investigate the changes over time across farm households (participants and non-participants) in terms of food security status. As far as my information is concerned, the practice of small-scale irrigation is long lived in the targeted study area. Thus, it would be much better if the extent of change in food security status of households due to participation in small scale irrigation relative to non-participants is analyzed over time.\n\nSuch longitudinal dataset can be accessed from the Ethiopian Statistical Service (ESS) annual surveys and/or from the World Bank living standard measurement study (LSMS). Specific comments for improvement\nPage 4 paragraph 3: the idea which is on rural industrial integration is not directly related to the research agendum raised here. So, the authors should modify this part. It should be clear that the paragraphs should be coherently linked across. If you refer to the paragraph 3 of same page, you can see that paragraph 4 is detached from the point presented in paragraph 3. Even the next paragraph is regarding small scale irrigation which is not related to paragraph 4. Page 7, table 2: the authors nicely measured food insecurity using ordinal scale (i.e. food secure, mildly food insecure, moderately food insecure and severely food insecure). However, when it comes to the logistic regression on page 10, they have considered food insecurity as binary. It would be good if the authors considered ordered logistic regression instead as it might give better insight on the extent and significance level of determinant factors across four groups of respondents.\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
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https://f1000research.com/articles/13-929
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https://f1000research.com/articles/12-844/v1
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18 Jul 23
|
{
"type": "Research Article",
"title": "Geographic distribution of conversion therapy prevalence in Canada. Findings from a national cross-sectional survey, 2020",
"authors": [
"Amrit Tiwana",
"Travis Salway",
"Julia Schillaci-Ventura",
"Sarah Watt",
"Travis Salway",
"Julia Schillaci-Ventura",
"Sarah Watt"
],
"abstract": "Background: Conversion therapy practices (CTPs) are discredited efforts that target lesbian, gay, bisexual, trans, queer, Two-Spirit, or other (LGBTQ2S+) people and seek to change, deny, or discourage their sexual orientation, gender identity, and/or gender expression. This study aims to investigate the prevalence of CTPs across Canadian provinces and territories and identify whether CTP bans reduce the prevalence of CTPs. Methods: We collected 119 CTPs from 31 adults (18+) in Canada who have direct experience with CTPs, know people who have gone to CTPs, or know of conversion therapy practitioners using a 2020 anonymous online survey. Mapping analysis was conducted using ArcGIS Online. CTP prevalence was compared between provinces/territories with and without bans using chi-square tests. Results: Three provinces and eleven municipalities had CTP bans. The prevalence of CTPs in provinces/territories with bans was 2.34 per 1,000,000 population (95% CI 1.65, 3.31). The prevalence of CTPs in provinces/territories without bans was 4.13 per 1,000,000 population (95% CI 3.32, 5.14). Accounting for the underlying population, provinces/territories with the highest prevalence of CTPs per 1,000,000 population were New Brunswick (6.69), Nova Scotia (6.50), and Saskatchewan (6.37). Conclusions: Findings suggest only 55% of Canadians were protected under CTP bans. The prevalence of CTPs in provinces/territories without bans was 1.76 times greater than provinces/territories with bans. CTPs are occurring in most provinces/territories, with higher prevalence in the west and the Atlantic. These findings and continued efforts to monitor CTP prevalence can help inform policymakers and legislators as society is increasingly acknowledging CTPs as a threat to the health and well-being of LGBTQ2S+ people.",
"keywords": [
"Canada",
"conversion therapy",
"LGBTQ2S+ health",
"health policy",
"public health",
"sexual and gender minorities",
"social epidemiology",
"spatial analysis"
],
"content": "Introduction\n\n“Conversion therapy” practices (CTPs) are widely discredited, yet they continue to occur across the globe, including Canada.1 CTPs refer to any practice designed to change, deny, or discourage: one’s feelings of sexual attraction to members of the same gender; lesbian, gay, bisexual, trans, queer, Two-Spirit, or other (LGBTQ2S+) identity; non-conforming gender expression; or gender identity that differs from sex at birth.2,3 These practices come in many forms and are also sometimes referred to by other names including sexual orientation and gender identity and expression change efforts (SOGIECE), aversion therapy, reparative therapy, and ex-gay ministries.4\n\nSOGIECE are not monolithic or clearly delineated practices, given that they can happen in many forms. In some contexts, a distinction between CTPs and SOGIECE is useful. CTPs are typically organized (i.e., structured activities) and circumscribed (e.g., a certain number of sessions with a practitioner); these practices are, metaphorically, only the “tip of the iceberg”.5 CTPs are underpinned by more prevalent practices including other forms of SOGIECE and cissexist and heterosexist attitudes. SOGIECE have a similar aim as CTPs, but also include practices that are less well defined and advertised. For example, a conversation between a parent and a child in which the child is dissuaded from living with or adopting a LGBTQ2S+ identity constitutes as SOGIECE. Overall, both CTPs and SOGIECE are enabled and condoned by widespread heterosexism and cissexism in societies.3\n\nCTPs are performed by licensed health care providers (e.g., psychologists, psychiatrists, and psychotherapists) and unlicensed practitioners.6 It has also been performed by ex-gay ministries (e.g., EXODUS) and religious leaders (e.g., pastoral counsellors).7 CTP attempts may also involve parents, government agencies, and school personnel.6 It may be performed one-on-one in an office or in groups at retreats or conferences.4 Providers may perform CTPs for money or for free.4 CTPs can include the use of aversive stimuli, individual talk therapy, participation in activities that are typically gendered by social norms and processes (e.g., sports, hunting, fishing, cooking, playing with dolls, etc.), forced sex, and praying and bible study.6\n\nThere is no credible scientific research that proves CTPs are psychologically safe or effective.8 Many medical and human rights associations (e.g., World Health Organization, Canadian Psychological Association, Canadian Psychiatric Association, American Medical Association, American Psychological Association, American Academy of Pediatrics, and Amnesty International) have denounced and discredited the effectiveness of CTPs.3,4,8,9 However, due to continuing discrimination and societal bias against LGBTQ2S+ people and others with non-heterosexual identities/attractions and non-cisgender identities/expressions, some practitioners continue to provide CTPs, particularly to minors, making them vulnerable to harms associated with these practices.9\n\nPrevious research suggests that CTPs negatively impact and stigmatize LGBTQ2S+ people, and can lead to increased anxiety, depression, self-hatred, post-traumatic stress disorder (PTSD), and many lifelong psychological and social issues.4,8–10 According to the Sex Now 2011/12 survey, exposure to SOGIECE among Canadian gay, bisexual, and other sexual minority men were positively associated with loneliness, regular illicit drug use, suicidal ideation, and suicide attempt.10\n\nLGBTQ2S+ health disparities are often conceptualized through the minority stress framework, in which mental health problems found among LGBTQ2S+ people are the result of chronic stressors stemming from the marginalized social status of these individuals, rather than a function of their identity itself.11–13 This framework offers some insight into the mechanisms through which CTPs may exact harm upon people who experience them.14 Minority stressors include prejudicial events and conditions that are expressed both interpersonally (e.g., violent attacks and discrimination) and structurally (e.g., laws allowing the rejection of LGBTQ2S+ people in employment).15 SOGIECE can also be conceptualized as a minority stressor because it promotes cisheteronormativity as the only acceptable way of life and reinforces the rejection of LGBTQ2S+ identities.15 Cisheteronormativity refers to “cissexism and heterosexism which assume cisgender gender identities and heterosexual orientation are more natural and legitimate than those of LGBTQ2S+ people”.5 As these stressors (including SOGIECE) accumulate, they create emotional (e.g., ruminating on negative messages), cognitive (e.g., feeling negatively about oneself and/or hopeless about one’s future), and social (e.g., social anxiety/avoidance) maladaptive responses, eventually leading to diagnosable conditions like anxiety or depression.14\n\nAccording to the survey results from Sex Now 2019 (SN2019), an estimated 50,000 Canadian gay, bisexual, and other sexual minority men have attended CTPs at some point in their lives.10 This corresponds to 1 in 10 gay, bisexual, and other sexual minority men (10%) having reported experiencing CTPs. In addition, the previous Trans PULSE Canada community-based survey found that 11% of transgender and non-binary people had undergone SOGIECE.16 Additionally, results from SN2019 suggest that transgender and non-binary people experience a higher burden of exposure to CTPs than cisgender people.17\n\nResults from SN2019 did not find a difference in the prevalence of CTPs across provinces and territories in Canada.10 However, it did find uneven exposure of CTPs across groups defined by age, gender identity, immigration, and ethnicity.10 CTPs were even more common (i.e., more than 10%) among subgroups including youth 15-19 years of age (13%), immigrants (15%), and racial/ethnic minorities (11-22%).17 Besides the annual Sex Now Surveys and Trans PULSE Canada Survey, no data are available regarding the distribution of CTPs in Canada. Further, no data are available examining the geospatial patterning of CTPs across and within different geographic regions of Canada, highlighting the importance of the current study.\n\nAs of November 11, 2021, five Canadian provinces and territories (Ontario, Nova Scotia, Prince Edward Island (PEI), Quebec, and Yukon) and dozens of Canadian municipalities (including Calgary, Edmonton, and Vancouver) have enacted legislative bans on CTPs.18 On December 4, 2021, the Canada House of Commons voted unanimously to pass Bill C-4, an Act to Amend the Criminal Code (conversion therapy). Bill C-4 subsequently was passed by the Senate and received Royal Assent on December 8, 2021. Bill C-4 includes provisions to prohibit causing a person to undergo CTP for, removing a child from Canada to undergo CTP outside Canada, and advertising or financially benefiting from CTP. This legislation represents an important milestone in the government’s commitment to protecting LGBTQ2S+ people. As policymakers and legislators are increasingly acknowledging CTPs as a threat to the health and well-being of LGBTQ2S+ people, up-to-date data on the geospatial patterns of CTP prevalence are urgently needed.\n\nGiven that CTPs are widely discredited and denounced practices, many conversion therapy providers do not advertise themselves as “conversion therapists”.19 Wide denunciation and steps towards criminalization may have led conversion therapy providers to operate ‘underground’ and advertise their services in covert ways.20 These providers may not refer to their services as “conversion therapy” and may instead use vague terms to allude to their approach to diverse sexual orientations or gender identities (e.g., healing “sexual brokenness”).20 For these reasons, it is challenging to track down the locations of where CTPs continue to operate. Establishing methods and data sources that enable ongoing monitoring of CTPs is critical in this context.\n\nFor this study, data were collected from a small national sample of Canadians who have direct experience with CTPs, know people who have gone to CTPs, or know of conversion therapy practitioners in 2020. The goal of the survey was to better understand the nature and scope of SOGIECE, or CTPs in Canada. The primary objective of this thesis was to estimate the spatial patterning of prevalent CTPs in Canada.\n\n\nMethods\n\nThis research uses a cross-sectional study design to examine the spatial prevalence of conversion therapy across Canadian provinces and territories. We asked Canadians who have direct experience with CTPs, know people who have gone to CTPs, or know of conversion therapy practitioners using an online survey. Participants were also asked to provide socio-demographic information such as age, sexual orientation, gender identity, race/ethnicity, and place of residence. This article was previously published as a preprint on medRxiv, a preprint server for health sciences.21 A novel questionnaire was developed with input from people who have directly experienced CTPs and from LGBTQ2S+ community partners. Wording of items was adjusted based on face validity considerations from these stakeholders. A copy of the questionnaire can be found under Extended data.29\n\nAn anonymous online survey using SurveyMonkey was conducted between August 18 and December 2, 2020. The survey was conducted in French and English. To be eligible for the survey, participants must have: experienced CTPs, nearly experienced CTPs or know someone who has experienced CTPs; been 19 years of age or older; and resided in Canada. The protocol for this study was approved by the Simon Fraser University Research Ethics Board (study 2019s0394).\n\nParticipants were recruited using various strategies including word-of-mouth (37% of respondents reported hearing about the survey by this manner), Twitter or Facebook (35%), LGBTQ2S+ community organizations (15%), and participation in an in-depth interview with the research team22 during January-July 2020 (13%). A total of N = 108 individuals entered the study, of which 19 did not consent to participate and/or were ineligible to participate. In total, N = 89 completed the entire survey (i.e., provided a response to the last question). For the present study, a subset of N = 31 (29%) of those who answered the questions regarding known conversion therapy providers in Canada were used in the analysis.\n\nParticipants were directed to a SurveyMonkey link where they were presented with an informed consent page regarding the study. Specifically, participants were informed about the project, who was conducting and funding the survey, the risks and benefits of the survey, as well as the eligibility criteria and consent to participate. All participants who completed the survey (N = 89) provided informed consent prior to completing the questionnaire. Participants were informed they could skip any of the questions they did not wish to answer.\n\nThe survey consisted of six parts: (1) recruitment and category of experience with conversion therapy; (2a) details about direct SOGIECE experience; (2b) details about knowledge of SOGIECE; (3) knowledge of conversion therapy practitioners; (4) legislative action against conversion therapy; and (5) social-demographic characteristics. To determine eligibility, participants were asked: “How would you describe your experience with conversion therapy (i.e., structured activity to deny or suppress your LGBTQ2 identity)? Please check all that apply.” Respondents were directed to part (3) of the survey, ‘knowledge of conversion therapy practitioners’, if they selected “I know of conversion therapy practitioners in Canada” or “I know that conversion therapy is happening in Canada”. They were then asked to list municipalities, provinces, and territories where these CTPs had taken place, and identify whether the practice was ongoing or historical (i.e., happened in the past).\n\nAt the end of the study, all participants were asked to provide social demographic information including their age, place of residence, and racial/ethnic group. Finally, participants were presented with a debriefing letter which included an option to input their email address to learn more about SOGIECE and CTPs, and a list of LBTQ2S+-affirming mental health supports for any participants who may have experienced distress because of the recalling of traumatic experience(s).\n\nTo analyze the spatial patterning, maps were created using ArcGIS Online. Participants who answered part (3) of the survey, ‘knowledge of conversion therapy practitioners’ (N = 31) were used in the mapping analysis. The dataset contained a total of 127 reports of 119 ongoing and 8 historical CTPs. Because names/addresses of CTPs were not collected, it was not possible to determine whether the 127 reports are mutually exclusive. Municipal and provincial/territorial spatial units were used in the analysis. Primary analysis focused only on ongoing reports, however additional maps were created combining ongoing and historical reports (see Extended Data).30 Thus, the primary analysis dataset consisted of 119 rows (i.e., observations) and 2 columns (reported municipalities and provinces/territories). These 119 CTPs were identified in 53 different municipalities (with 1-7 CTPs per municipality) and 8 different provinces/territories (with 1-28 CTPs per province/territory). 20 out of the 119 reports identified CTPs in provinces/territories but did not specify a municipality.\n\nThree maps were created: (1) municipal, provincial and territorial CTP bans in Canada, (2) a heat map of ongoing CTPs (using municipal spatial unit), and (3) a choropleth map of CTP prevalence by province/territory (calculated as reports of ongoing CTPs divided by 1,000,000 population per province/territory). Provinces/territories with numerators less than 5 were not interpreted due to statistical instability. As of November 2021, data on current legislative bans were obtained from the Legislation Map on the No Conversion Canada website (Wells, n.d.). The “heat map” function in ArcGIS Online was applied to identify hot spots of CTPs across the nation. The map of the bans and the heat map were compared to assess the association between ongoing CTPs and existing bans. We also calculated the prevalence of CTPs in provinces/territories with bans and the prevalence of CTPs in provinces/territories without bans (as of the time of survey, August 2020) using chi-square tests, to assess differences in prevalence between these two sets of jurisdictions. 95% confidence intervals were added to these measures. The 2016 Census cartographic boundary file by Statistics Canada was used to estimate the population per municipality, province, and territory for the choropleth map.23\n\n\nResults\n\nThe age of respondents ranged from 18 to 65+ with 70% of participants under age 45. The majority of the respondents resided in the most populous Canadian provinces, i.e., British Columbia, Ontario, and Alberta. The majority of the sample identified with a white ethnic/racial group (93.33%), followed by East Asian, Black, and mixed ethnic/racial groups. A plurality of respondents identified as cis men (38.7%) and gay (41.9%). However, reported gender identity and sexual orientation were diverse, as shown in Table 1.\n\n* Participants permitted to select more than one option.\n\nData collection took place between August and December 2020, therefore legislative bans passed on CTPs after August 2020 are not considered in the results. At that point in time, only three provinces (Ontario, PEI, and Nova Scotia) and eleven municipalities had legislative bans in place. As shown in Table 2, 19,459,172 out of 35,151,728 Canadians were protected under legislative bans as of August 2020, which corresponds to 55.1% of the total Canadian population. Figure 1 is a map visualizing the bans passed as of August 2020.\n\n31 out of the 89 participants who answered part (3) of the survey, ‘knowledge of conversion therapy practitioners’ reported 119 CTPs (reports per participant ranged from 1-31, mean of 4). 20 (16.8%) locations were reported at the provincial/territorial level and 99 (83.2%) locations were reported at the municipal level. As shown in Table 3, the prevalence of ongoing CTPs in provinces and territories with bans as of August 2020 is 2.34 per 1,000,000 population (95% CI 1.65, 3.31). The prevalence of ongoing CTPs in provinces and territories without bans as of August 2020 is 4.13 per 1,000,000 population (95% CI 3.32, 5.14). No data were reported regarding CTPs in the Northwest Territories and Nunavut and therefore are not included in the calculations.\n\nA heat map was created to examine a more granular prevalence of reported ongoing CTPs in Canada using count data without adjustment of the underlying population. We used the municipal spatial unit for the heat map because data containing just the reported province/territory were misleading. As shown in Figure 2, ongoing CTPs were identified across the nation. Many of the cases and hotspots are clustered around the South of Canada. This is no surprise given that two-thirds (66%) of the Canadian population lives within 100 kilometres of the southern Canada-United States (US) border, an area that represents approximately 4% of Canadian land.24\n\nNote. No data were reported regarding the prevalence of CTPs in the Northwest Territories and Nunavut.\n\nFigure 3 displays the prevalence of CTPs divided by 1,000,000 population per province/territory. When accounting for the underlying population, the provinces and territories with the highest prevalence of reported ongoing CTPs are New Brunswick (6.69), Nova Scotia (6.50), and Saskatchewan (6.37). Provinces and territories with moderate prevalence include British Columbia (6.08), Alberta (5.90), and Manitoba (3.91), Provinces with lower prevalence include Ontario (2.01), and Quebec (1.59). The following provinces/territories had <5 reports of conversion practices and therefore are not further interpreted: Yukon (55.75), PEI (7.00), and Newfoundland and Labrador (1.92). No data were reported regarding the prevalence of ongoing CTPs in the Northwest Territories and Nunavut.\n\nNote. *Province/territory has implemented a ban as of August 2020. Please exercise caution in interpreting estimates from the following provinces/territories with numerators <5: Yukon (YT) (55.75), Prince Edward Island (PEI) (7.00), Newfoundland and Labrador (NL) (1.92). No data were reported regarding the prevalence of CTPs in the Northwest Territories and Nunavut.\n\n\nDiscussion\n\nThis non-probabilistic survey of adults in Canada with direct or indirect experiences of CTPs provides early insights on the spatial patterning of the prevalence of CTPs in Canada. Findings suggest only 19,459,172 out of 35,151,728 Canadians were protected under legislation on CTPs at the time of the study. This number corresponds to 55.1% of the total Canadian population protected. Further, CTPs are occurring in majority of Canadian provinces and territories, with higher prevalence in the west and the Atlantic.\n\nThese findings are similar to the results of a study which examined exposure to psychological attempts to change a person’s gender identity from transgender to cisgender (PACGI) among transgender people in the US, lifetime and between the years 2010 and 2015, by US state.24 The findings from this study suggested that practices continue to occur in every US state as recently as the period 2010 to 2015, despite major US medical organizations identifying PACGI as ineffective25 and legislative bans passed in 20 states and more than 100 municipalities in the US.26 As with the Canadian map (see Extended Data),30 The PACGI study found elevated prevalence of PACGI in western jurisdictions of the US.\n\nThe prevalence of CTP in provinces/territories without legislative bans as of August 2020 was approximately 1.76 times greater than the prevalence in provinces/territories with bans (Ontario, PEI, Nova Scotia). While this is encouraging, there are several reasons to be cautious in interpreting this finding. The data used in this analysis does not allow us to control for other factors happening within the provinces/territories with bans that have deterred CTPs (i.e., confounding). For example, we did not account for whether there might have been an effect of municipal bans. Additionally, we cannot know from these data whether bans are enforced. We cannot say whether legislative bans caused CTPs to shut down because we do not know whether these services started or stopped practicing before or after the bans. In other words, we cannot assess the temporal relationship between time and practices taking place. For these reasons, the association between the lower prevalence found in provinces/territories with bans and higher prevalence found in provinces/territories without bans may not be real.\n\nFirst, the sample size was small. The prevalence calculated may be unstable because it is based upon only a small number of reported CTPs extrapolated over a large population.27 Second, the sample largely came from LGBTQ2S+ community organizations or conversion therapy survivors and thus constitutes a non-probabilistic subset of the total target population (e.g., all people in Canada). Evidence shows non-probability surveys tend to overrepresent employed, high-income-earning, and gay-identified sexual minorities.28 Third, since the survey was developed in Vancouver, British Columbia, it is likely more CTPs were reported in this region compared to other parts of Canada, which is reflected in the geographic patterning of the data. Fourth, the language of the item used to measure conversion therapy may not encompass people’s experiences. For example, people may interpret their experience as more of a form of SOGIECE rather than conversion therapy and thus may choose to not report the practice. Lastly, we cannot assess legislation impacts and whether it reduced the prevalence of CTPs because we do not know if the identified practice took place before or after legislation was passed.\n\nGiven that CTPs persist across Canada, we recommend that the following actions be taken in collaboration with conversion therapy survivors, community organizations and multiple levels of government. The results of this study should be confirmed and repeated with a larger sample size to ensure underscore representativeness. One idea to deal with the small sample size problem is to bring additional years of data into the analysis to increase the size of the numerator.27 In addition to this, recruitment methods should be expanded to make interpretations more generalizable to the Canadian population. There must be continued efforts to monitor how conversion therapy practitioners continue to operate, even in places where bans have been implemented. Monitoring where CTPs continue to occur will help keep legislators accountable and identify where supportive LGBTQ2S+-affirming environments are most needed.\n\n\nConclusion\n\nThe ongoing occurrence of CTPs is a serious public health issue impacting the health and well-being of thousands of LGBTQ2S+ Canadians. Findings from this study should be taken into consideration as Bill C-4 is implemented and enforced in Canada. Combined with legislative ban efforts, the Canadian government should work to deter SOGIECE and CTPs, while encouraging LGBTQ2S+-affirming environments by supporting gay straight alliances, pride flags and other interventions that remind LGBTQS2+ people that their identities are valid.3 Finally, education is required to reduce the prejudice of LGBTQ2S+ people to ultimately put an end to CTPs.\n\nThe protocol for this study was approved by the Simon Fraser University Research Ethics Board (study 2019s0394).",
"appendix": "Data availability\n\nDue to the sensitive nature of this research, participants in this study did not agree for their data to be shared publicly. Aggregated data that support the findings of this study are available from the principal investigator (TS) upon reasonable request. Additional requests for data must be directed to the SFU Research Ethics Board, dore@sfu.ca.\n\nTiwana A, Salway T, Schillaci-Ventura J, & Watt S. (2023). Survey About “Conversion Therapy” in Canada. Zenodo. https://doi.org/10.5281/zenodo.7981897. 29\n\nTiwana A, Salway T, Schillaci-Ventura J, & Watt S. (2023). Sensitivity analysis: ongoing and historical conversion therapy practices (CTPs) in Canada. Zenodo. https://doi.org/10.5281/zenodo.8136543. 30\n\nThis project contains the following extended data:\n\n• Questionnaire.pdf\n\n• Sensitivity analysis figures\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nSee STROBE guideline attached separately. Repository name: STROBE checklist and flowchart for geographic distribution of conversion therapy prevalence in Canada.\n\n\nAcknowledgements\n\nOur research team is grateful to the following individuals who provided insight and feedback on the questionnaire drafts, and/or who helped to promote the survey and have given permission to be named in this article: A.J. Lowik, Beth Carlson-Malena, David Kinitz, Elisabeth Dromer, Geron Malbas, Keith Murray, Kiffer Card, Michael Kwag, Nicholas Schiavo, and Trevor Goodyear.\n\n\nReferences\n\nBishop A: The Global Reach of So-Called Conversion Therapy. OutRight Action International; 2019. Reference Source\n\nAshley F: Model law – prohibiting reparative practices. SSRN Electron. J. 2019. Publisher Full Text\n\nCentre for Gender and Sexual Health Equity: Ending conversion therapy in Canada: Survivors, community leaders, researchers, and allies address the current and future states of sexual orientation and gender identity and expression change efforts.2020 Feb 18. Reference Source\n\nThe Trevor Project: About Conversion Therapy.2020 Dec 20. Reference Source\n\nKinitz DJ, Goodyear T, Dromer E, et al.: “Conversion therapy” experiences in their social contexts: A qualitative study of sexual orientation and gender identity and expression change efforts in Canada: Les Expériences de “thérapie de conversion” dans leur contexte social: Une étude qualitative des efforts de changement de l’orientation sexuelle, de l’identité de genre et de l’expression de genre au Canada. Can. J. Psychiatr. 2021; 67: 441–451. Publisher Full Text\n\nAdamson TM, Wallach S, Garner A, et al.: The global state of conversion therapy - a preliminary report and current Evidence Brief.2020. Publisher Full Text\n\nKarten EY, Wade JC: Sexual orientation change efforts in men: A client perspective. J. Mens Stud. 2010; 18(1): 84–102. Publisher Full Text\n\nWells K: Conversion therapy in Canada: A guide for legislative action. Revised Edition.MacEwan University; 2020. Reference Source\n\nThe Human Rights Campaign: The lies and dangers of “conversion therapy”.Reference Source\n\nSalway T, Ferlatte O, Gesink D, et al.: Prevalence of exposure to sexual orientation change efforts and associated sociodemographic characteristics and psychosocial health outcomes among Canadian Sexual Minority men. Can. J. Psychiatr. 2020; 65(7): 502–509. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGreen AE, Price-Feeney M, Dorison SH, et al.: Self-reported conversion efforts and suicidality among US LGBTQ youths and young adults, 2018. Am. J. Public Health. 2020; 110(8): 1221–1227. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMeyer IH: Prejudice, social stress, and Mental Health in lesbian, gay, and bisexual populations: Conceptual issues and research evidence. Psychol. Bull. 2003; 129(5): 674–697. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRich AJ, Salway T, Scheim A, et al.: Sexual minority stress theory: Remembering and honoring the work of Virginia brooks. LGBT Health. 2020; 7(3): 124–127. PubMed Abstract | Publisher Full Text\n\nHatzenbuehler ML: How does sexual minority stigma “get under the skin”? A psychological mediation framework. Psychol. Bull. 2009; 135(5): 707–730. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBlosnich JR, Henderson ER, Coulter RW, et al.: Sexual orientation change efforts, adverse childhood experiences, and suicide ideation and attempt among sexual minority adults, United States, 2016–2018. Am. J. Public Health. 2020; 110(7): 1024–1030. Publisher Full Text\n\nThe Trans PULSE Canada Team: QuickStat #1 - Conversion Therapy.2019 Dec 12. Reference Source\n\nSalway T, Juwono S, Klassen B, et al.: Experiences with sexual orientation and gender identity conversion therapy practices among sexual minority men in Canada, 2019–2020. PLoS One. 2021; 16(6): e0252539. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWells K: Legislation Map. No Conversion Canada.Reference Source\n\nBrush J: Conversion Ministries and Ex-Gay Ministries. Ohio Psychological Association; 2021 Jan 29. Reference Source\n\nTiwana A: Identifying harmful “conversion therapy” practices in all its forms. MindMapBC; 2021 Oct 2. Reference Source\n\nTiwana A, Salway T, Schillaci-Ventura J, et al.: Geographic distribution of conversion therapy prevalence in Canada. MedRxiv. 2022. Publisher Full Text\n\nGoodyear T, Kinitz DJ, Dromer E, et al.: “They want you to kill your inner queer but somehow leave the human alive”: Delineating the impacts of sexual orientation and gender identity and expression change efforts. J. Sex Res. 2021; 59: 599–609. Publisher Full Text\n\nStatistics Canada: 2016 Census Boundary Files.2019 Nov 19. Reference Source\n\nStatistics Canada: The Daily – Population size and growth in Canada.2017 Feb 10. Reference Source\n\nTurban JL, King D, Reisner SL, et al.: Psychological attempts to change a person’s gender identity from transgender to cisgender: Estimated prevalence across US states, 2015. Am. J. Public Health. 2019; 109(10): 1452–1454. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBorn Perfect: Conversion Therapy Bans by U.S. State.2021 Oct 8. Reference Source\n\nGreen C: Geographic Information Systems and Public Health: Benefits and Challenges. National Collaborating Centre for Infectious Diseases. 2012; 37: 1–12.\n\nSalway TJ, Morgan J, Ferlatte O, et al.: A systematic review of characteristics of nonprobability community venue samples of sexual minority individuals and associated methods for assessing selection bias. LGBT Health. 2019; 6(5): 205–215. PubMed Abstract | Publisher Full Text\n\nTiwana A, Salway T, Schillaci-Ventura J, et al.: Survey About “Conversion Therapy” in Canada. Zenodo. 2023. Publisher Full Text\n\nTiwana A, Salway T, Schillaci-Ventura J, et al.: Sensitivity analysis: ongoing and historical conversion therapy practices (CTPs) in Canada. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "211737",
"date": "04 Oct 2023",
"name": "Sean Mulcahy",
"expertise": [
"Reviewer Expertise Human rights and law reform for LGBTIQA+ communities."
],
"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 important research on the geographic distribution of conversion therapy practices in Canadian provinces and territories with and without a ban on these practices.\nThe article could be strengthened by addressing the following points.\nFirst, what is the nature of bans in those jurisdictions which have them? For example, do they extend to trans/two spirit communities (as the Manitoba non-legislative ban appeared to only extend to sexual orientation)? Are they only focussed on clinical settings (for example, precluding conversations between a child and a parent)?\nSecond, what available information is there on enforcement of bans? For example, are there crime statistics or sentencing data available? Third, what is the effect of municipal (as opposed to provincial or territorial) bans? In this respect, it would be useful to include a full list of municipalities that have enacted legislative bans (and the provinces or territories they are in), particularly given the research found that there were conversion therapy practices in, on average, about 7 municipalities in each province or territory identified.\nFourth, whilst the study lists limitations, some of these should be extended as noted. Per limitations 1 and 2, the sample size was indeed very small, being based on a study of 31 participants (though understanding the difficulty of attracting participants research of this kind), and a very proactive cohort making on average 4 reports of conversion therapy practices each (and up to 31). Per limitation 4, another limitation of the survey method is that people have different conceptual understandings of what amounts to a conversion therapy practice and may report practices that do not amount to conversion therapy. Some further limitations also need to be noted: (a) as the study states earlier, \"it was not possible to determine whether the... reports were mutually exclusive\" meaning that the same practice could have been reported multiple times thus over-emphasising the prevalence of conversion therapy practices in a particular province or territory; (b) conclusions about Prince Edward Island cannot be reached because it was excluded (as one of the \"provinces/territories [that] had <5 reports of conversion practices and therefore are not further interpreted\").\nFifth and finally, the study notes that \"results from SN2019 did not find a difference in the prevalence of CTPs across provinces and territories in Canada.\" Obviously, this study challenges that finding, so it would be useful to articulate why SN2019 did not find a geographic difference and what the possible limitations of that study could be compared to this.\nThe study ends with strong conclusions and possible directions for future research, proving the utility and importance of research of this kind.\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": "12185",
"date": "15 Aug 2024",
"name": "Amrit Tiwana",
"role": "Author Response",
"response": "First, we have added the following explanatory text to the Introduction (see page 4): “This federal law defined CTP in relation to both sexual orientation and gender identity. While provincial/territorial bans have predominantly focused on clinical settings, the federal law applies to all settings, including those outside licensed healthcare. However, informal practices like parent-child conversations are typically not covered by these bans. Nonetheless, legislation represents an important milestone in the government’s commitment to protecting LGBTQ2S+ people.” Second, to the best of our knowledge, there has been little to no enforcement of bans. Crime statistics are not yet available, though these could be reported in the future (e.g., by Statistics Canada). The absence of these data further motivates community surveys like the one we conducted. We have added the following line to the Introduction (see page 5): “Moreover, official data on enforcement of bans are absent, and many who experience CTP may choose not to disclose their experiences owing to feelings of shame.” Third, we have included a list of municipalities with bans in Table 2. We have added detail regarding the typical mechanism of municipal bans on page 4: “Municipal bans typically operate through prohibition of CTP under bylaws governing the provision of business licenses.” Fourth, we have included these in the limitations section on page 14: “Fifth, it was not possible to determine whether the reports were mutually exclusive. This means that the same practice could have been reported multiple times, potentially overemphasizing the prevalence of CTPs in a particular province or territory. Sixth, conclusions about certain regions, such as Prince Edward Island, cannot be reached because they were excluded from the analysis due to having fewer than five reports of CTPs. This exclusion could lead to an incomplete estimation of the prevalence and distribution of CTPs across Canada.” Fifth, we have added why SN2019 did not find geographic differences and what the possible limitations of that study could be compared to ours. This new addition can be found on page 13: “On the other hand, the SN2019 study did not find a difference in the prevalence of CTPs across provinces and territories in Canada. The difference in findings between SN2019 and our study may be due to differences in survey methodologies or sample sizes, as our study used a more targeted approach to recruit participants with direct or indirect experiences of CTPs.”"
}
]
},
{
"id": "234559",
"date": "09 Feb 2024",
"name": "Benjamin Harrell",
"expertise": [
"Reviewer Expertise I am an economist studying sexual and gender minority population health. I specialize in mental healthcare",
"health policy",
"and the demography of SGM people. In relation to this paper",
"I have presented work on the effects of CTP bans in the United States and their effects on suicidality and mental 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\nSummary: The study presents the results of a non-probabilistic survey of Canadian adults who either (a) have experienced conversion therapy practices (CTPs) or (b) know someone who has. Importantly, this study generates key knowledge about the geospatial distribution of CTPs across Canada. This is important context because not all territories and provinces ban CTPs, leaving important gaps in legal protections for sexual and gender minorities (SGM). The findings are stark: Only 55.1% of Canadians enjoy protections from CTP, with the highest prevalence of CTPs occurring in the west and the Atlantic regions. Similarly, the findings suggest that protections are imperfectly binding, these practices are still occurring in regions which ban them, albeit at much lower rates--in regions without bans, CTPs occur at 1.76 times the rate of regions WITH bans.\nAssessment: This important study provides important context to the growing global literature around the prevalence, consequences, and harms of CTPs and other forms of sexual orientation and gender identity change efforts (SOGICE). The study also comes with key limitations. The most immediate limitation of the study is that statistics are derived from a small sample size. Prevalence rates could be biased by the relatively young sample (about 3/4 are younger than 50) and non-representativeness of provincial or territorial residence (there were no responses from Saskatchewan Manitoba, or the territories), Similarly, the sampling strategy (mostly Vancouver, BC based community organizations or CTP survivors) could bias the estimates in ways that are not clear. It could be the case that this survey underestimates the prevalence of CTP due to its under-representativeness of rural SGM, but it could also overestimate the prevalence of CTP due to its focus on survivors of CTP, especially since CTP is known to be correlated with suicidality.\nDespite these limitations, which are both well-documented by authors, and contextualized as directions for future research, this study is a significant contribution to a fundamental question in this research space: WHERE is CTP happening, as much as to whom.\nA note on data availability: While there is no data made available for replication of this study, the authors make a compelling case for non-inclusion. The data is inherently sensitive and many participants did not provide consent to share their data. However, the authors do provide instructions on how to acquire aggregated data sufficient to qualitatively replicate this 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?\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": "234548",
"date": "20 Feb 2024",
"name": "Travis Scheadler",
"expertise": [
"Reviewer Expertise sport for social justice",
"LGBTQ+ activism and health",
"LGBTQ+ policies"
],
"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 aimed to estimate the spatial patterning of conversion therapy practices (CTPs) in Canada. Overall, the study is well-written and has important policy and research implications. There are a few notes (see below) that should be addressed to improve the quality of the manuscript. These are all relatively minor.\n\nPlease add a sentence clarifying what you mean by \"tip of the iceberg.\" I understand this is minor, but can help ensure readers unfamiliar with CTPs understand exactly what is being conveyed.\n\nPlease make sure there is consistency in verb tense. The first sentence says \"CTPs are\" and the second says \"It has\" - determine whether CTPs are/is plural or singular. Be sure to check for consistency throughout the manuscript.\n\nThe first paragraph under \"The harms of conversion therapy\" is excellent! This is very succinct and straightforward. Great job!\nConsider revising the first sentence in the second paragraph under \"Attempts to ban conversion therapy.\" Changing \"are widely discredited and denounced practices\" to \"have been banned in many parts of Canada\" will smooth the transition between these paragraphs and help narrow down the problem to the specific purpose of this study. The beginning of this sentence currently seems more connected to the first half of the Introduction on the generalized harms of CTPs rather than the legislative bans in Canada.\n\nChange was to were in the second sentence of the first paragraph under Measures.\n\nTable 2 would be less wordy if columns 1 and 2 are switched. For instance, merge all the cells for Alberta to avoid repeating \"Alberta\" 11 times.\n\nChange \"conversion practices\" to CTPs in the sentence that starts with \"The following provinces/territories had <5 reports of conversion practices.\"\n\nThe figures are all great visualizations!\nDelete or reword \"lifetime and between the years 2010 and 2015, by US state\" in the second paragraph of the Discussion. This part of the sentence is cumbersome and confusing to read. Also, in the following sentence, change \"the findings from this study\" to \"the authors.\" Some readers may mistake \"findings from this study\" as findings from YOUR current study. Please also consider changing \"continue to occur in every US state as recently as the period 2010 to 2015\" to \"continued to occur in every US state between 2010 and 2015.\" Then, consider the following revision for the last part of the sentence: \"even though major US medical organizations have identified PACGI as ineffective and 20 states and more than 100 municipalities throughout the US have banned PACGI.\" These changes should improve the readability of this paragraph by offering more consistency in the different lists provided. Another note - 22 states have now banned licensed professionals from providing conversion therapy to minors. Additionally, please be sure to cite the correct sources. The 24th reference is related to the population size of Canada and is unrelated to PACGI in the United States. Be sure to check all references to make sure they are aligned. Note: this is why I marked \"partly\" to the first question about whether current literature is cited.\n\nIn the final paragraph before limitations - be careful not to undersell yourself. I appreciate the clarity around how to interpret the findings, but I also think there is room here for a call to action. Consider adding a paragraph - or even just a sentence or two - calling for bans against CTPs in the areas where it is most prevalent. I see that this was briefly mentioned in the Conclusion. I think there is room for it here as well.\n\nAdd a general sentence to start the limitations section. This can simply be \"the present study is not without limitations\" or some similar version of this. For the third limitation, add \"especially given that some participants were recruited through word-of-mouth.\" This should help clarify a little more why this is a limitation.\n\nDelete the term \"underscore\" in the second sentence under future 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? 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": "12186",
"date": "15 Aug 2024",
"name": "Amrit Tiwana",
"role": "Author Response",
"response": "To clarify what we mean by “tip of the iceberg”, we have included a detailed version of the previous sentence on page 3: “CTPs are typically organized (i.e., structured activities) and circumscribed (e.g., a certain number of sessions with a practitioner); these practices are, metaphorically, only the “tip of the iceberg”, representing visible and formally recognized forms of efforts to change LGBTQ2S+ identities.” Thank you for pointing out the inconsistency in verb tense. We have reviewed the manuscript and ensured that the subject \"CTPs\" is consistently treated as a plural noun throughout. We have updated the verb tense to maintain consistency, so all instances now read \"CTPs are\" or \"CTPs have.\" We have changed the sentence accordingly so that it is more connected to the legislative bans in Canada rather than the first half of the introduction on the generalized harms of CTPs. This can be found on page 5: “Given that CTPs have been banned in many parts of Canada, many conversion therapy providers do not advertise themselves as “conversion therapists”. We have changed “was” to “were” in the second sentence of the first paragraph under Measures. Thank you for this suggestion regarding the format of Table 2. We discussed it as a team of authors and decided the current ordering—by date of enactment—makes it easy for the reader to see how the cumulative protections accrued over time; therefore, we have left the table as is. We have changed “conversion practices” to “CTPs” on page 12: “The following provinces/territories had <5 reports of CTPs and therefore are not further interpreted: Yukon (55.75), PEI (7.00), and Newfoundland and Labrador (1.92). No data were reported regarding the prevalence of ongoing CTPs in the Northwest Territories and Nunavut.” We have revised the second paragraph of the Discussion section to improve clarity and readability. We removed the phrase \"lifetime and between the years 2010 and 2015, by US state\" and rephrased it to better convey the intended meaning. Additionally, we replaced \"the findings from this study\" with \"the authors\" to avoid any potential confusion. The sentence now reads: \"The authors explored this issue between 2010 and 2015 across US states, finding that PACGI continued to occur in every state between 2010 and 2015, even though major US medical organizations have identified PACGI as ineffective and 22 states and more than 100 municipalities throughout the US have banned PACGI.\" We also corrected the reference citations to ensure accuracy and alignment with the content. Thank you for this feedback. We have incorporated your feedback using a few sentences in the last paragraph for the limitations. This can be found on page 13: “Despite this, our study emphasizes the urgent need for nationwide legislative bans against CTPs in Canada. Areas without bans continue to experience significantly higher prevalence rates, highlighting the ongoing harm inflicted on LGBTQ2S+ individuals. Comprehensive bans, along with rigorous enforcement and support for affected communities, are essential steps toward mitigating these harmful practices and promoting inclusive and affirming environments nationwide.” We have added a sentence at the beginning of the paragraph on the limitations. This can be found on page 13: “The present study is not without limitations.” The word “underscore” has been deleted. The sentence is now changed to “The results of this study should be confirmed and repeated with a larger sample size to ensure representativeness.\""
}
]
}
] | 1
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https://f1000research.com/articles/12-844
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https://f1000research.com/articles/11-1241/v1
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01 Nov 22
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{
"type": "Research Article",
"title": "Cointegration and causality relationship of Indian stock market with selected world markets",
"authors": [
"Farman Ali",
"Pradeep Suri",
"Tarunpreet Kaur",
"Deepa Bisht",
"Pradeep Suri",
"Tarunpreet Kaur",
"Deepa Bisht"
],
"abstract": "Background: The purpose of this study is to explore the trends and causes of established and emerging nations' stock market integration with India. The National Stock Exchange (NSE) indices act as a counterweight to international market indices. This study investigates the sustained interest of foreign investors in the Indian stock market in the wake of capital market reforms, as well as whether it moves in tandem with other markets in Asia and the United States. Methods: Our study examined the possibility of cross-country cointegration between the largest economies and indices around the world using multiple financial econometric models, such as Augmented Dickey-Fuller, Unit Root, Correlation, and Johansen Cointegration. Results: The findings of this study significantly support the notion that Indian and international financial markets are highly integrated. Vector error correction model indicates that the Indian market (NSE) is highly cointegrated with the US market (National Association of Securities Dealers Automated Quotations) and increased volatility signifies global contagion. Conclusion: A cursory examination of the data reveals distinct investment and portfolio diversification options for global investors. This could assist regulators in formulating more effective rules regarding price discovery processes.",
"keywords": [
"Stock market",
"Investors",
"Volatility",
"Global market",
"Unit root test",
"VECM",
"Johansen cointegration test"
],
"content": "Introduction\n\nAn economic spillier occurs when one event sets off another event in a similar way, having an impact on economies both within and outside a country. In 2008, when Lehman Brothers collapsed in the U. S, the domino effect hit the economies worldwide including India (Aloui et al., 2016). Financial markets today are closely interconnected and driven by trust. Therefore, the developed and emerging markets have been a riveting field for the research of behavioural finance due to interlinked stock markets across the world. Lai et al. (2016) examined during the crisis, investors make errors of judgment as long as a group of investors takes irrational decisions that lead to worsening the situation of the stock market.\n\nCOVID-19 also delivered a shock to the economies of most countries, because of the nature of the interconnected global market (Karkowska & Urjasz, 2021). The Indian stock market has been broadly resilient amidst the COVID-19 crisis so far, despite the devastating waves of the pandemic (Kapoor et al., 2020). However, the Indian economy has witnessed some impact from the global crash. Seth & Panda (2020) discussed that it is hard to pinpoint exactly the impact of any financial crisis on the Indian stock market, but it seems that the COVID-19 crisis has spilled over into some sectors. Numerous studies (Shaikh, 2021; Dhall & Singh, 2020; Singh & Neog, 2020) have argued on insignificant causal linkage of the stock markets across the world. Some authors such as Zhang & Hamori (2021), have also focused on the possible factors and impacts of the global crisis on the Indian market. Several studies have identified both short-term and long-term cointegration and interconnected financial markets between different economies of the world (Stawiarski, 2021;Yarovaya & Lau, 2016). The global financial markets are closely interconnected and driven by the emotions of the investors (Huang et al., 2020). Hence, this manuscript focuses a causal linkage and cointegration between the global crisis and the Indian stock. In previous studies such as Mukherjee & Bose (2008) and Rajwani & Mukherjee (2013), Asian economies have been integrated with the economies of developed nations such as Japan and the United States.\n\nIn this study, we contribute to the literature on strategic financial decision-making for investors. Using vector auto regressive correlation (VAR) and vector error correction method (VECM) to assess the cointegration, (Yarovaya & Lau, 2016; Kanjilal & Ghosh, 2017; Aggarwal & Raja, 2019) have documented the multivariate cointegration-vector auto-regression method and their results indicate that the Indian stock market return depends on the world market returns. This study’s main objective is to comprehend how the volatility index of the Indian stock market might be impacted by the volatility index of some other countries.\n\n\nLiterature review\n\nA series of recent studies (Choudhary & Singhal, 2020; Kumar et al., 2021; Sahoo & Kumar, 2021; Kartal et al., 2022) has investigated the cointegration relationship of the stock market amid crisis. Some studies (He et al., 2020; Stawiarski, 2021) have explained the causal linkage of Indian stock market with Asian countries while in some other studies, a number of authors have recognized the comprehensive analysis by applying Generalized Autoregressive Conditional Heteroskedasticity Model (Narasimha & Mushinada, 2020) and found very high volatility index of Indian stock market in comparison to developed countries during the COVID-19 crisis. While recent advances in the field of behavioural finance have highlighted the volatility clustering in the Indian stock market through the use of time series data analysis and predictive analytics. According to Khaing et al. (2020), stock trend extraction results matched genuine price movement. These patterns were retrieved with the news effect curve during the global recession 2008-2009. These criteria include timestamp conversion, identifying the necessary verb, stock reference, and identifying advanced trends. Chen (2021) created the new neural network model to develop the prediction model’s concepts. Belciug et al. (2021) evaluated the efficacy of a statistical learning framework using an algorithm based on a competitive/collaborative method for generating a reliable real-time forecast of the next stock market transaction price for a share during upswing of the market. Biswas et al. (2021) reviewed numerous models and approaches used in stock market prediction and focused on their advantages and disadvantages during the crisis. Numerous studies have argued that there is insignificant (Goudarzi & Ramanarayanan, 2011) and significant (Aggarwal & Raja, 2019) causal linkage among the stock markets across the world. Some scholars, such as Jain & Biswal (2016), have also focused on the possible drivers of rupee value decline and the influence of the 2014-2015 global crisis on the Indian stock market. The global financial markets are closely interconnected Muthukumaran et al. (2011) and driven by the emotions of the investors. Several studies have identified interconnected financial markets between different economies of the world during1996-1997 crisis Yang et al. (2003) by applying VAR (vector auto-regression). Ahmad et al. (2005) have investigated only short term linkage whilst no significant linkage was found among the Indian Stock Market (NSE), Japanese (Nikkei) and US equity market (Dow Jones) amid crisis by using Granger-causality test. Menon et al. (2009) found that the Indian stock market did not have any causal linkage with the US and Japanese stock markets during the 2008 crisis period by hypothesizing Engle Granger test of co-integration. Siddiqui (2009) concluded that the Indian stock market is integrated with the global market. Some others studies such as Rajwani & Mukherjee (2013) have argued the Indian stock market is not interconnected with the Asian markets. Narayan et al. (2014) have investigated highly positive time varying bilateral correlations by analysing GARCH-dynamic conditional correlations.\n\nYarovaya & Lau (2016) have concluded the asymmetric causality linkage; their results indicating the coupling and decoupling of the Chinese stock market with the UK stock market. Nayak et al. (2016) applied machine learning algorithms and identified that the historical prices of the stocks are combined with sentiments of the investors. Nandy & Chattopadhyay (2019) have explained the unidirectional action from the world’s stock exchange indices over Indian stock market indices by carrying multivariate vector auto regression (VAR) analysis and Granger causality test. Aggarwal & Raja (2019) explored a long-run cointegration equation of the Asian and the Indian market by applying the Johansen cointegration model. Some other studies have also confirmed the bidirectional causality of Bombay Stock exchange indices with the US stock market indices by carrying Granger causality test (Choudhary & Singhal, 2020). Seth & Panda (2020) have revealed the strong dynamic linkage between the global economies and Indian economy by analysing the Autoregressive (AR1), Generalized Auto Regressive Conditional Heteroskedasticity (GARCH 1,1) Model and Asymmetric Dynamic Conditional Correlation (ADCC) model to determine the coupling and decoupling. Apart from analysing only the degree of cointegration and contagion among the world market, several studies have hypothesized the global contagion on the volatility of Indian stock’s prices. Li et al. (2011) have confirmed that the GARCH model cannot completely account for all nonlinearity in simulated market amid global crisis. Goudarzi & Ramanarayanan (2011) have revealed the bilateral causality between the Bombay Stock Exchange and foreign institutional investors. Garg & Gulati (2013) examined the rationality of the Indian investors in the face of economic crisis and validated the use of rational pricing models. Ding et al. (2014) have indicated returns depend on the direction of the movement of buying and selling pattern and stock distinctiveness of individual holdings and on arbitrage constraint. Guyon (2014) suggested the models of path-dependent volatility provide excellent alternatives to the duopoly of local volatility and stochastic volatility that has dominated option pricing for the past twenty years.\n\nThe fractal structure has been studied by (Mahalingam & Selvam, 2014) with long term returns on the market. An adaptive multiplicative error model (MEM) with time-varying parameters was proposed by Härdle et al. (2015). A multiplicative error model (MEM) parameters are adaptively estimated through sequential testing. Bir et al. (2015) have investigated the highest volatility for open ended stocks in the Indian stock market. Kumari & Mahakud (2016) have explored the unidirectional causality between sentiment and stock market volatility. This study indicated that the market reacts more strongly to the impact or shock of negative or bearish mood than to positive or bullish sentiment. Bouri et al. (2017) have examined significant hypothesis about the existence of cointegration linkage and nonlinear volatilities of oil and gold in Indian stock market during the crisis. Abuzayed et al. (2018) demonstrated that the skewed Student-t FIGARCH model generates the most precise VAR forecast for a single day. Other studies have demonstrated the ripple effects of United States of America uncertainty on other developed markets, such as L. Fang et al. (2018). Boako & Alagidede (2018) have confirmed the correlation amongst African stock markets, regional and global markets by carrying a comprehensive analysis. Chuliá et al. (2018) have demonstrated that some crises have had a weak negative correlation with market synchrony. Wang et al. (2019) have confirmed that significant shocks have a substantial link with stock prices and assert that volatility is more susceptible to the asymmetric effect than extreme volatility. According to Xing & Yang (2019), firms that attract more individual investors provide higher returns with lower future stock price crash risk. It is widely accepted that a greater degree of correlation among stocks provides an early warning of the probability of crashes. It has been conclusively shown that herding is strongly evident during the fluctuations of market (Shantha, 2019).\n\nSome studies such as Fang et al. (2020) also identified that the long-term volatility of the stock market depends upon many macroeconomic variables. Lyócsa & Molnár (2020) found that the autoregressive coefficient was negative during COVID-19 (November 2019 to May 2020) with but the stock market uncertainty and fear of virus highly affected the breath of the autoregressive coefficient amidst the COVID-19 crisis. Narasimha & Mushinada (2020) point out that investors are concerned about cognitive biases and therefore adapt to changing market dynamics. (Vo, 2020) studied the significant positive link between foreign investors and crash risk due to the asymmetry of information in the emerging market. Among BRICS (Brazil, Russia, India, China, and South Africa) a diverse responses to the stock market volatility reported including negative and positive shocks (Salisu & Gupta, 2020). Cui & Zhang (2020) have suggested that negative information creates fear among the investor which leads to a larger stock price crash risk. Nikkinen & Peltomäki (2020) have focused on investors’ crash worries and utilised data on published newspaper articles and web search volumes to address the complex relationship between information supply and demand connected to investor anxiety and their consequences on realised stock market returns, implying and finding that the media contribute to the efficiency of the stock market by enhancing the transmission of information. He et al. (2020) have examined the futures markets ability to price discover by margin trading on the stock market. Kumar & Misra, (2020) have found widespread evidence of long-term similarity among the NIFTY 50 index and the global market. Naik et al. (2020) used GARCH (Generalized Auto-Regressive Conditional Heteroskedasticity) to calculate stock return error distribution. When time series data are heteroskedastic and volatile, the GARCH model is best. GARCH effectively predicted stock market crises (1995-2019) using State Bank of India and Infosys datasets. Elyasiani et al. (2021) analysed market greed by including the skewness index, which measures investor enthusiasm as opposed to investor fear. Previous studies have mainly exclusively explored the integration of Asian economies with other developed nations such as the United States and Japan during the period from 3rd January 2011 to 29th December 2017 in the midst of a global financial crisis. According to the literature, during the COVID-19 crisis, domino effects had both short-term and long-term negative consequences on economies all around the world (Salisu & Gupta, 2020).\n\nHowever, there is a contradiction in the argument made by Aggarwal & Raja (2019); Rajwani & Mukherjee (2013) and Menon et al. (2009). Long-term cointegration of stock markets was not discovered, but correlation analysis revealed that stock market integration was growing with time.\n\nEven though the majority of the COVID-19 economic crisis has passed, further research is still needed on the developed and rising Asian markets. In addition, it would be interesting to know whether the effect of the crisis on the Indian stock market persists over time and, if so, for how long. Do the recent shocks to global markets alter the standard deviation of forecasting errors in the Indian stock market? Contributing to existing theory and strategic financial decision-making for investors, this paper offers valuable insights. In particular, the authors explore how the global volatility index’s shock influences the Indian volatility index, how long the impact lasts, and the degree and sign of the effect.\n\n\nMethods\n\nIn our study, we examined data from several major indices, including the NSE in India, the NIKKEI (Japan’s Nikkei 225 Stock Average) in Japan, NASDAQ (National Association of Securities Dealers Automated Quotations), DJI (Dow Jones Industrial Average) and S&P (Standard and Poor index) in the United States, the FTSE (Financial Times Stock Exchange) in the UK, the DAX (Deutscher Aktien Index) in Germany, the FTXIN (FTSE–Xinhua China A50 Index) in China, Cotation Assistée en Continu (CAC) benchmark of France stock market and the Hang Seng in Hong Kong. The descriptive statistics for all indexes’ returns are shown in Table 3. We compiled and collected the data from different websites (including Yahoo, Investing.com and NSE India) over the long-term, encompassing a significant portion of the recession from January 1, 2008, to December 2, 2021. The time period covered by the research has been selected to provide an in-depth look at the worldwide correlations that have an effect on the Indian stock market over the long term. Although the trading hours of each stock exchange varies, the time frame is the exact same for all indexes. Therefore, in order to examine the group statistics, we have taken the common sample. We calculated the daily return by applying the [Return=log (Closing price of indices/Closing price of indices (-1))] equation over the closing price. We analysed the data using the EViews 12 (University Version) software package. The student version of this software is freely available (https://eviews.com/download/student11/). The Johansen cointegration test (Menon et al., 2009)1 is used to demonstrate a long-term link between variables. To determine short-term and long-term associations between variables, the vector error correction model was utilised followed by Ezeibekwe (2021).\n\nH0: There is no long-term linear interdependency between the NSE index and the global index.\n\nH1: There is a long-term linear interdependency between the NSE index and the global index.\n\nThis model is adopted when variables are cointegrated. VAR indicates the cointegration of the variables over the short term. In addition, by incorporating error correction terms, the model examines the long-term causal relationship. The number of variables can be measured by using the equations below. The vector autoregressive model of order 1 is called VAR (1):\n\nEngle-Granger model is used to measure (Stawiarski, 2021) cointegration between the indices from the NSE and global indices such as Japan (NIKKEI), U.S. (NASDAQ, DJI, and S&P), UK (FTSE), Germany (DAX), China (FTXIN), Hong Kong (HANG SENG) and France (CAC). In 1981, Granger introduced the concept of cointegrated multivariate time series to demonstrate linear combinations of stationary variables imply that there is a long-term relationship (Engle et al., 1987).\n\nA regression model must have stationary conditions to prevent spurious regressions. Our study examines stationary conditions by using the ADF test (Augmented Dickey-Fuller) (Cheng et al., 2021). The null hypothesis is rejected if the ADF value (calculated) is less than the critical levels (1%, 5%, and 10%). The cointegration test follows the unit root test for measuring the extent of co-movement of long-term relationships among indices (Cheng et al., 2021).\n\nIn Johansen cointegration2, the number of independent linear combinations (k) that give a stationary process is determined for (m) time series variables. The results are given as cointegration ranks. There is no cointegration relationship when the rank is 0, and there is a cointegration equation when the rank is 1, and so on. Johansen cointegration test analyses the relationship between the NSE index and global index by using Eigen-values and trace statistics. Integration is based on how many times a series need to be differentiated to produce a stationary series. The first difference generates an integrated series known as I (1). As a result, a time series with I (0) is stationary; if I (1), the level is stationary and the change is stationary. The equation below determines cointegration:\n\nNull Hypothesis; H0: When k = 0, then p = m, there is no linkage among the variables3.\n\nAlternate Hypothesis; H1: 0 < k < m, 0 < p < m There is a significant linkage among the variables.\n\nIndividual observations show large shifts during crisis times are further followed by large shifts in the return of the NSE indices and the global indices representing the wild and calm periods of volatility clustering. Figure 1 shows the clustering of the volatility for the daily return of indices, firstly noted by Mandelbrot & Taylor (1967) ‘large changes tend to be followed by large changes, of either sign, and small changes tend to be followed by small changes.’ Figure 2 represent the leptokurtic statistical distributions with kurtosis greater than three results to a greater extent of volatility because of positive or negative shocks in the stock market. While the Jerque-Bera of NSE daily return (32031.42) measures the high volatility. The shape of the curve and the value of kurtosis along with the low probability value reveal the possibility for the rejection of the null hypothesis. The skewness measures the asymmetry of a time series over a given period (normal skewness; 0, positive skewness; long right tail, negative skewness; long left tail).\n\nTable 1 indicates that the left-hand tail of the German Blue chip stock market (DAX) is smaller than the right-hand tail. In other indices, a negative skewness (the left-hand tail is larger than the right-hand tail) indicates a scenario of small wins and few large losses for investors. Table 1 provides descriptive statistics on daily returns, highlighting Jarque-Bera standard deviation using the same sample for all indices. The NSE returns over the entire period sample shows a negatively skewed distribution of the sample (Jaque-Bera 33817.66, standard deviation 0.013768, Kurtosis 20.31397). In Japan, the statistical moments of the NIKKEI were Jarque-Bera 5525.19, standard deviation 0.0151, and Kurtosis 10.171). Jarque-Bera values for US Market (NASDAQ; 10447.74, standard deviation 0.014376, and Kurtosis 17.26778), (S&P; 23085.57, standard deviation 0.013164), and (DJI; 33669.34, standard deviation 0.012713, and Kurtosis 20.25097). These all show a similar leptokurtic distribution with negative skewness.\n\nIt is evident from the descriptive statistics that the significant value probabilities and the Jerque-Bera calculation indicate that the residual distribution of daily returns, like other indices (FTSE) Jarque-Bera 13203.88, standard deviation 0.012250 with Kurtosis value 13.81124), Germany (DAX) Jarque-Bera 9850.239, standard deviation 0.014335 with Kurtosis value 12.34726), Hong Kong (HANG SENG) Jarque-Bera 11642.69, standard deviation 0.0126 and Kurtosis 19.89 and France (CAC) Jarque-Bera 8553.046. The values of skewness’ and kurtosis observed the volatility clustering and specify the distribution of all indices (variables) is leptokurtic. Only Germany (DAX) is positively skewed, which specify that the huge gain covers the small losses of investors. The Indian stock market exhibits a positive correlation with the world market, as seen in Table 2; however, the correlation of all variables is not strong enough to explain the cointegration.\n\nTable 2 examines the correlation trends between the Indian market and a few selected global markets, indicating that there is a relationship between the Indian stock market and other markets; nevertheless, Figure 3 illustrates that this connection is sometimes parallel to the global economy.\n\nIt is said that the “flap of a butterfly’s wings in Brazil could set off a tornado in Texas” (Lorenz, 2000) that’s not true in the Indian context. The Indian stock market is still linked to the world market because the NSE has a positive correlation with all global indexes, despite the fact that this correlation has been reducing significantly.\n\nA unit root test determines whether a time series is stationary. The null hypothesis defines time series as having a unit root, while the alternative hypothesis defines them as being stationary. Table 3 indicates the value of t statistics in all variables exceeds the critical value.\n\n* MacKinnon (1996) one-sided p-values.\n\nIn this case, these variables were tested again at a difference of one, and the result indicated a null hypothesis, i.e., that the series of all variables are integrated over four lag of order one. To perform Johansen’s cointegration test we employed the VAR lag order selection criterion. Table 4 identifies the AIC value at the third lag so we examined the cointegration test by using the third lag, recommended by AIC. A Japanese statistician (Akaike, 1974) developed the Akaike information criterion. It currently serves as a paradigm for the foundations of statistics and is also commonly employed for statistical inference. The Akaike information criterion (AIC) is an estimator of prediction error and, therefore, relative model quality for a given set of data. Given a set of data models, AIC determines the quality of each model in comparison to the other models. When a statistical model is employed to depict the process that generated the data, the representation is virtually never perfect; as a result, some information is lost. AIC assesses the relative amount of information lost by a particular model; the less information a model loses, the higher the model’s quality.\n\n* Indicates lag order selected by the criterion (each test at 5% level).\n\n\nResults\n\nTable 5 shows the statistical values of Johansen’s cointegration test. In addition, it provides information about the maximum Eigen-value. Statistics for all variables dependent (NSE) and independent (World’s indices) demonstrate a perfect correlation of cointegration. Since the calculated value of statistics and maximum Eigen-value are greater than the critical value (at 5% level) of (MacKinnon et al., 1999), the null hypothesis of no cointegration is rejected in favour of the alternative hypothesis of cointegration. Therefore, the Indian stock market and the global stock market have ten cointegration equations.\n\n* Denotes rejection of the hypothesis at the 0.05 level.\n\n** MacKinnon-Haug-Michelis (1999) p-values.\n\nIn Figure 4, we show impulse response functions associated with the non-factorized one standard deviation of innovations for the Indian stock market and the stock markets of some of India’s top trading partners and developed nations. It depicts the negative impulse responses of the Chinese and Japanese stock markets. Interestingly, both markets are responding similarly to a shock to the Indian stock market in their respective stock markets. Geographic proximity may be the reason for this. The established stock markets of the United States and other economies have a distinct trend. It demonstrates that these markets are in fact developed and have a robust positive impulse reaction to the Indian stock market.\n\nThis study shows innovations in the Indian stock market do indeed propagate to India’s top trading partner’s stock markets in a time-varying manner. In this study, the U.S. stock market appears to be the most influential. The analysis of the ADF statistics (Table 3) confirmed the unit root series for all indices and then we determined lag order using the VAR Lag Order Selection Criteria (Table 4) to carry out causality test. To perform the cointegration test, we selected the AIC, indicating the third lag. Table 5 reveals the critical value is less than trace statistics and Max-Eigen values, which rejects the null hypothesis of no causal links, resulting in cointegration equations among all variables. Panel C of Table 6 predicts the long-term cointegration equation for the Indian stock market, which suggests that Japan (NIKKEI), US (NASDAQ, DJI, UK (FTSE), Germany (DAX), Hong Kong (HANG SENG) and France (CAC) indices have a positive correlation with Indian Indices (NSE), while China (RFTXIN) and US (S&P) indices have a negative correlation, considering ceteris paribus on Indian stock market. As Song et al. (2021) have documented supporting evidence, our findings are consistent with the idea that global financial crises have positively influenced interdependence of stock markets in Asian countries. Based on the coefficients, the linkage between the Indian stock market and the global market is statistically significant at a 1% level. Additionally, the Chinese stock market indices and S&P show a negative impact on Indian stock markets and the NASDAQ and Dow Jones indices in the US, Hong Kong (HANG SENG), and Japan (NIKKEI) have shown the strongest long-term correlation with Indian markets. The impulse reaction of NIKKEI to unit shock in NSE causes a little decrease in NSE on days 3 and 4, but an increase on day 6. Between days 8 and 10, this effect increases marginally. Similarly, when a unit shock is applied to NSE, NIKKEI displays a mixed reaction. This is evidence that the Japanese and Indian stock markets are not fully integrated. The impulse response of S&P to a unit shock on the NSE demonstrates that it has a negative impact on the SENSEX on the second day and a positive impact on the third day. It indicates that the NSE is highly cointegrated with the S&P and in the same way, DJI, NASDAQ, FTSE, and CAC. In addition, HNGSNG, DAX, and FTXIN do not have a significant impact on the Indian stock market. Similar findings are reported by Choudhary & Singhal (2020) and Mukherjee & Bose (2008). The correlation results are consistent with Seth & Panda (2020) indicated that the Indian stock market index has a strong positive correlation with the US stock market index.\n\n\nConclusion\n\nThe empirical findings suggest that the selected stock markets have a long-term dynamic. According to our research, the volatility of the US stock market considerably affected the Indian stock market. We performed a vector error correction model test to assess the stationary conditions of the series. This test demonstrated that the sequence is stationary. However, the variables become constant after taking into account the original difference. Cointegration tests show that the Indian stock market is integrated over time owing to the presence of a cointegration vector. A model of error correction demonstrates conclusively that variables are causal in the long-term. The stock market in India is impacted by those in the United States, Great Britain, Japan, and Germany. In addition, we applied the pairwise Granger causality test, which reveals the lead-lag connection across the markets, to test for short-term causative and informational linkages among diverse pairs of markets. According to our findings, the Indian stock market is neither fully connected nor completely decoupled from the global market. Nonetheless, the amount of integration implies that portfolio diversification can still result in substantial risk reduction and return maximisation in both the short-term and long-term by diversifying their portfolio during a crisis. In recent years, the returns on major US stock indices have dominated the returns for Indian stocks. Similar results show that the bank-dominated financial sectors of the ASEAN five and China are increasingly integrated (Caporale et al., 2021).\n\nThe study is prone to various limitations because it relies on secondary sources of data, which have inherent limitations, such as the total number of trading days during the study period for each country were different. So, the sample was adjusted with the help of EViews software. A quick glance at the study highlights clear-cut investment and portfolio diversification opportunities for international investors. This may help regulators formulate better policies concerning price discovery mechanisms. Moreover, it is possible to extend the present study to include global contagion issues between the sample countries. This could be done using high frequency data.\n\n\nData availability\n\nFigshare: Cointegration and Causality Relationship, https://doi.org/10.6084/m9.figshare.20263803.v2 (Ali et al., 2022).\n\nThis project contains the following underlying data:\n\n• CHINA A 50(FTXIN9).xlsx\n\n• DAX.xlsx\n\n• NIKKEI.xlsx\n\n• NSE.xlsx\n\n• S&P 500.xlsx\n\n• CAC 40 (FCHI).xlsx\n\n• DJI.xlsx\n\n• HANG SENG.xlsx\n\n• NASDAQ 100.xlsx\n\n• FTSE.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nAbuzayed B, Al-Fayoumi N, Charfeddine L: Long range dependence in an emerging stock market’s sectors: volatility modelling and VaR forecasting. Appl. Econ. 2018; 50(23): 2569–2599. Publisher Full Text\n\nAggarwal S, Raja A: Stock market interlinkages among the BRIC economies. Int. J. Ethics Syst. 2019; 35(1): 59–74. Publisher Full Text\n\nAhmad KM, Ashraf S, Ahmed S: Is the Indian Stock Market Integrated with the US and Japanese Markets?: An Empirical Analysis. South Asia Econ. J. 2005; 6(2): 193–206. Publisher Full Text\n\nAkaike H: A new look at the statistical model identification. IEEE Trans. Autom. Control. 1974; 19(6): 716–723. Publisher Full Text\n\nAli F, Dr. Suri P , Dr. Kaur T , et al.: Cointegration and Causality Relationship. figshare. Dataset.2022. Publisher Full Text\n\nAloui R, Gupta R, Miller SM: Uncertainty and crude oil returns. Energy Econ. 2016; 55: 92–100. Publisher Full Text\n\nBELCIUG S, SĂNDIȚĂ A, COSTIN H, et al.: Competitive/Collaborative Statistical Learning Framework for Forecasting Intraday Stock Market Prices: A Case Study. Stud. Inform. Control. 2021; 30(2): 43–54. Publisher Full Text\n\nBir R, Trivedi J, Antonescu M: Modeling S & P Bombay Stock Exchange BANKEX Index Volatility Patterns Using GARCH Model. Procedia Econ. Financ. 2015; 32(15): 520–525. Publisher Full Text\n\nBiswas M, Nova AJ, Mahbub MK, et al.: Stock Market Prediction: A Survey and Evaluation. 2021 International Conference on Science & Contemporary Technologies (ICSCT). 2021; 1–6.\n\nBoako G, Alagidede P: African stock markets in the midst of the global financial crisis: Recoupling or decoupling? Res. Int. Bus. Financ. 2018; 46: 166–180. Publisher Full Text\n\nBouri E, Jain A, Biswal PC, et al.: Cointegration and nonlinear causality amongst gold, oil, and the Indian stock market: Evidence from implied volatility indices. Res. Policy. 2017; 52(November 2016): 201–206. Publisher Full Text\n\nCaporale GM, Gil-Alana LA, You K: Stock Market Linkages between the Asean Countries, China and the US: A Fractional Integration/cointegration Approach. Emerg. Mark. Financ. Trade. 2021; 1–14. Publisher Full Text\n\nChen S: Correlation analysis of financial indicators and stock price fluctuations based on artificial intelligence system. 2021 International Conference on Artificial Intelligence and Smart Systems (ICAIS). 2021; 43–46.\n\nCheng T, Liu J, Yao W, et al.: The impact of COVID-19 pandemic on the volatility connectedness network of global stock market. Pac. Basin Financ. J. 2021; 101678.\n\nChoudhary S, Singhal S: International linkages of Indian equity market: evidence from panel co-integration approach. J. Asset Manag. 2020; 21(4): 333–341. Publisher Full Text\n\nChuliá H, Pinchao AD, Uribe JM: Risk Synchronization in International Stock Markets. Glob. Econ. Rev. 2018; 47(2): 135–150. Publisher Full Text\n\nCui H, Zhang Y: Does investor sentiment affect stock price crash risk? Appl. Econ. Lett. 2020; 27(7): 564–568. Publisher Full Text\n\nDhall R, Singh B: The COVID-19 Pandemic and Herding Behaviour: Evidence from India’s Stock Market. Millennial Asia. 2020; 11(3): 366–390. Publisher Full Text\n\nDing C, Wang HJ, Lee MC, et al.: How does the change in investor sentiment over time affect stock returns? Emerg. Mark. Financ. Trade. 2014; 50(SUPPL. 2): 144–158. Publisher Full Text\n\nElyasiani E, Gambarelli L, Muzzioli S: The skewness index: uncovering the relationship with volatility and market returns. Appl. Econ. 2021; 53(31): 3619–3635. Publisher Full Text\n\nEngle RF, Granger CWJ, Engle BYRF, et al.: Co-Integration and Error Correction: Representation, Estimation, and Testing Published by: The Econometric Society Stable. 1987; 55(2): 251–276.Reference Source\n\nEzeibekwe OF: Stock Market Development and Economic Growth in Nigeria: Evidence from Vector Error Correction Model. J. Dev. Areas. 2021; 55(4): 103–118. Publisher Full Text\n\nFang L, Qian Y, Chen Y, et al.: How does stock market volatility react to NVIX ? Evidence from developed countries. Physica A. 2018; 505: 490–499. Publisher Full Text\n\nFang T, Lee T, Su Z: Jou rna lP. J. Empir. Financ. 2020. Publisher Full Text\n\nGarg A, Gulati R: Do investors herd in Indian market. Decision. 2013; 40(3): 181–196. Publisher Full Text\n\nGoudarzi H, Ramanarayanan CS: Empirical Analysis of the Impact of Foreign Institutional Investment on the Indian Stock Market Volatility during World Financial Crisis 2008-09. Int. J. Econ. Financ. 2011; 3(3): 214–226. Publisher Full Text\n\nGuyon J: Path-Dependent Volatility. SSRN Electron. J. 2014; 1–12. Publisher Full Text\n\nHärdle WK, Hautsch N, Mihoci A: Local adaptive multiplicative error models for high-frequency forecasts. J. Appl. Econ. 2015; 30(4): 529–550. Publisher Full Text\n\nHe F, Liu-Chen B, Meng X, et al.: Price discovery and spillover dynamics in the Chinese stock index futures market: a natural experiment on trading volume restriction. Quant. Finance. 2020; 20(12): 2067–2083. Publisher Full Text\n\nHuang Z, Tang Q, Huang S: Foreign investors and stock price crash risk: Evidence from China. Econ. Anal. Policy. 2020; 68: 210–223. PubMed Abstract | Publisher Full Text\n\nKanjilal K, Ghosh S: Dynamics of crude oil and gold price post 2008 global financial crisis – New evidence from threshold vector error-correction model. Res. Policy. 2017; 52(March): 358–365. Publisher Full Text\n\nKapoor V, Dey S, Khurana AP: Modeling the influence of world stock markets on Indian NSE index. J. Stat. Manag. Syst. 2020; 23(2): 249–261. Publisher Full Text\n\nKarkowska R, Urjasz S: Connectedness structures of sovereign bond markets in Central and Eastern Europe. Int. Rev. Financ. Anal. 2021; 74(June 2020): 101644. Publisher Full Text\n\nKartal MT, Ayhan F, Kirikkaleli D: Regime-switching effect of COVID-19 pandemic on stock market index: evidence from Turkey as an emerging market example. Macroeconomics and Finance in Emerging Market Economies. 2022; 1–18. Publisher Full Text\n\nKhaing ET, Thein MM, Lwin MM: Enhance Trend Extraction Results by Refining with Additional Criteria. International Conference on Computational Collective Intelligence. 2020; 777–788. Publisher Full Text\n\nKumar G, Misra AK: Long run commonality in Indian stocks: empirical evidence from national stock exchange of India. J. Indian Bus. Res. 2020; 12(4): 441–458. Publisher Full Text\n\nKumar S, Choudhary S, Singh G, et al.: Crude oil, gold, natural gas, exchange rate and indian stock market: Evidence from the asymmetric nonlinear ARDL model. Res. Policy. 2021; 73(June): 102194. Publisher Full Text\n\nKumari J, Mahakud J: Investor Sentiment and Stock Market Volatility: Evidence from India. J. Asia Pac. Bus. 2016; 17(2): 173–202. Publisher Full Text\n\nLai HC, Tseng TC, Huang SC: Combining value averaging and Bollinger Band for an ETF trading strategy. Appl. Econ. 2016; 48(37): 3550–3557. Publisher Full Text\n\nLi H, Wang S, Shang W: Heterogeneity, nonlinearity and endogenous market volatility. J. Syst. Sci. Complex. 2011; 24(6): 1130–1142. Publisher Full Text\n\nLorenz E: The butterfly effect. World Scientific Series on Nonlinear Science Series A. 2000; 39: 91–94.\n\nLyócsa Š, Molnár P: Stock market oscillations during the corona crash: The role of fear and uncertainty. Financ. Res. Lett. 2020; 36: 101707. Publisher Full Text\n\nMacKinnon JG, Haug AA, Michelis L: Numerical distribution functions of likelihood ratio tests for cointegration. J. Appl. Econ. 1999; 14(5): 563–577. Publisher Full Text\n\nMahalingam G, Selvam M: Stock Market Reaction during the Global Financial Crisis in India: Fractal Analysis. Asia-Pac. J. Manag. Res. Innov. 2014; 10(4): 403–412. Publisher Full Text\n\nMandelbrot B, Taylor HM: On the distribution of stock price differences. Oper. Res. 1967; 15(6): 1057–1062. Publisher Full Text\n\nMenon NR, Subha MV, Sagaran S: Cointegration of Indian stock markets with other leading stock markets. Stud. Econ. Financ. 2009; 26(2): 87–94. Publisher Full Text\n\nMukherjee P, Bose S: Does the stock market in India move with Asia? A multivariate cointegration-vector autoregression approach. Emerg. Mark. Financ. Trade. 2008; 44(5): 5–22. Publisher Full Text\n\nMuthukumaran T, Raja AS, Palanichamy P: Impact of Global Financial Crisis on Indian Stock Market — An Analytical Study. Asia Pac. Bus. Rev. 2011; 7(2): 5–12. Publisher Full Text\n\nNaik N, Mohan BR, Jha RA: GARCH Model Identification for Stock Crises Events. Procedia Computer Science. 2020; 171(2019): 1742–1749. Publisher Full Text\n\nNandy S, Chattopadhyay AK: ‘Indian Stock Market Volatility’: A Study of Inter-linkages and Spillover Effects. J. Emerg. Mark. Finance. 2019; 18(2_suppl): S183–S212. Publisher Full Text\n\nNarasimha V, Mushinada C: Journal of Behavioral and Experimental Finance Are individual investors irrational or adaptive to market dynamics? J. Behav. Exp. Financ. 2020; 25: 100243. Publisher Full Text\n\nNarayan S, Sriananthakumar S, Islam SZ: Stock market integration of emerging Asian economies: Patterns and causes. Econ. Model. 2014; 39: 19–31. Publisher Full Text\n\nNayak A, Pai MMM, Pai RM: Prediction Models for Indian Stock Market. Procedia Comput. Sci. 2016; 89: 441–449. Publisher Full Text\n\nNikkinen J, Peltomäki J: Crash Fears and Stock Market Effects: Evidence From Web Searches and Printed News Articles. J. Behav. Financ. 2020; 21(2): 117–127. Publisher Full Text\n\nRajwani S, Mukherjee J: Is the Indian stock market cointegrated with other Asian markets? Manag. Res. Rev. 2013; 36(9): 899–918. Publisher Full Text\n\nSahoo S, Kumar S: Existence of Cointegration between the Public and Private Bank Index: Evidence from Indian Capital Market. Adv. Decis. Sci. 2021; 25(4): 152–172. Publisher Full Text\n\nSalisu AA, Gupta R: Jo ur na l P re of. Glob. Financ. J. 2020; 100546. Publisher Full Text\n\nSeth N, Panda L: Time-varying Correlation Between Indian Equity Market and Selected Asian and US Stock Markets. Glob. Bus. Rev. 2020; 21(6): 1354–1375. Publisher Full Text\n\nShaikh I: On the relation between Pandemic Disease Outbreak News and Crude oil, Gold, Gold mining, Silver and Energy Markets. Res. Policy. 2021; 72(March): 102025. PubMed Abstract | Publisher Full Text\n\nShantha KVA: The evolution of herd behavior: Will herding disappear over time? Stud. Econ. Financ. 2019; 36(3): 637–661. Publisher Full Text\n\nSiddiqui S: Stock Markets Integration: Examining Linkages between Selected World Markets. Vision J. Bus. Perspect. 2009; 13(1): 19–30. Publisher Full Text\n\nSingh MK, Neog Y: Contagion effect of COVID-19 outbreak: Another recipe for disaster on Indian economy. J. Public Aff. 2020; 20(4): e2171–e2178. PubMed Abstract | Publisher Full Text\n\nSong Y, Huang R, Paramati SR, et al.: Does economic integration lead to financial market integration in the Asian region? Econ. Anal. Policy. 2021; 69: 366–377. Publisher Full Text\n\nStawiarski B: Granger Causality and Cointegration During Stock Bubbles and Market Crashes. Workshop on Nonstationary Systems and Their Applications. 2021; 93–107.\n\nVo XV: Foreign Investors and Stock Price Crash Risk: Evidence from Vietnam. Int. Rev. Financ. 2020; 20(4): 993–1004. Publisher Full Text\n\nWang L, Ma F, Liu J, et al.: Forecasting stock price volatility: New evidence from the GARCH-MIDAS model. Int. J. Forecast. 2019; 36: 684–694. Publisher Full Text\n\nXing K, Yang X: How to detect crashes before they burst: Evidence from Chinese stock market. Physica A: Statistical Mechanics and Its Applications. 2019; 528(55): 121392. Publisher Full Text\n\nYang J, Kolari JW, Min I: Stock market integration and financial crises: The case of Asia. Appl. Financ. Econ. 2003; 13(7): 477–486. Publisher Full Text\n\nYarovaya L, Lau MCK: Stock market comovements around the Global Financial Crisis: Evidence from the UK, BRICS and MIST markets. Res. Int. Bus. Financ. 2016; 37: 605–619. Publisher Full Text\n\nZhang W, Hamori S: International Review of Financial Analysis Crude oil market and stock markets during the COVID-19 pandemic: Evidence from the US, Japan, and Germany. Int. Rev. Financ. Anal. 2021; 74(February): 101702. Publisher Full Text\n\nZhao S, Chen X, Zhang J: The systemic risk of China’s stock market during the crashes in 2008 and 2015. Physica A: Statistical Mechanics and Its Applications. 2019; 520: 161–177. Publisher Full Text\n\n\nFootnotes\n\n1 Menon et al. (2009) hypothesize that the Indian equity market have insignificant causal relationship with the US and Japanese equity markets during the crisis period by adopting the “Engle-Granger test” of co-integration. Yarovaya & Lau (2016) also examined the asymmetric causality test results supporting evidence of the coupling and decoupling hypothesis.\n\n2 A long-term equilibrium relationship between security margin trading and systemic risk volatility demonstrated by the Johansen co-integration test. (Zhao et al., 2019) Johansen’s cointegration test indicates an average relationship between the Indian and Shanghai stock markets and an especially strong relationship between the Indian and Singapore stock markets. A Granger causality test indicates that margin financing contributes to the volatility of systematic risk in a bear market.\n\n3 Mukherjee & Bose (2008) posited cointegration, vector auto-regression, vector error-correction models, and Granger causality and found that the U.S. market leads all Asian markets in terms of information."
}
|
[
{
"id": "172401",
"date": "22 May 2023",
"name": "Uttam Golder",
"expertise": [
"Reviewer Expertise My research interest is Fintech",
"Environmental",
"and Climate Financing. I also have an interest in Growth and Banking related 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\nReview Report on Cointegration and causality relationship of Indian stock market with selected world markets\nThe researcher has identified an interesting topic related to the Cointegration and causality relationship of Indian stock market with selected world markets. Thanks to the authors for their effort. However, from my side, some critical issues in the article have been focused:\nAbstract\nOverall the formation of the abstract is correct. However, the authors should indicate the nature and types of the data. Also, they should mention the date range.\nIntroduction\nThe introduction part of the paper is very much simplified. It only provided the overall background of the study, and the problem statement was not fully clear to me. However, it fails to signify it's uniqueness and contribution to the respective fields of knowledge. Also, there is no indication for whom this study is important and in which way it is essential. Besides, what is the study's implication, application, and utility?\n\nThe authors have said, \"Some authors such as Zhang & Hamori (2021), have also focused on the possible…\". But they only cite two authors of an article. They should cite some more articles.\n\nPlease include a separate paragraph with the structure of your remaining work in this study.\nLiterature review\nThe authors have said, \"The global financial markets are closely interconnected Muthukumaran et al. (2011) and driven by the emotions of the investors…\" The citation and formation of the sentence are not correct. Please correct it.\n\nThe authors have said, \"Several studies have identified interconnected financial markets between different economies of the world during the during1996-1997 crisis Yang et al. (2003) by applying VAR (vector auto-regression)\". The citation and formation of the sentence are not correct. Please correct it.\n\nThe citation style is wrong in several places of your work; for example, you have said \"Some others studies such as Rajwani & Mukherjee (2013) have argued…\". This will be as Rajwani and Mukherjee (2013). This type of mistake is all over the documents. Please check the whole paper, and correct it carefully.\n\nAs FIGARCH is used for the 1st time in this article, please use its full form.\n\nThe authors have said, \"Some studies such as Fang et al. (2020) also identified that…\". However, the authors said some studies but mentioned only one article. Why? Please mention some others.\n\nI do not understand the meaning of your followings sentence, please rewrite it: \"Lyócsa & Molnár (2020) found that the autoregressive coefficient was negative during COVID-19 (November 2019 to May 2020) with but the stock market uncertainty and fear of virus highly affected the breath of the autoregressive coefficient amidst the COVID-19 crisis.\"\n\nThe following sentence it too large. Please rewrite it: \"Nikkinen & Peltomäki (2020) have focused on investors’ crash worries and utilised data on published newspaper articles and web search volumes to address the complex relationship between information supply and demand connected to investor anxiety and their consequences on realised stock market returns, implying and finding that the media contribute to the efficiency of the stock market by enhancing the transmission of information.\"\n\nAt the end of the literature review section, the laps and gaps of the previous study should be identified, but there is no discussion like that. Moreover, the authors have only explained the previous study's empirical results, but there are no critical arguments against the work done previously.\nMethods\nAuthors have cited Engle-Granger model. But did not cite the article, rather the citation style is wrongly placed. He wrote: “Engle-Granger model is used to measure (Stawiarski, 2021) cointegration between…”. But (Stawiarski, 2021) should be place at last of the sentence, and also Engle-Granger original paper should be cited where they currently cited (Stawiarski, 2021), on in the place of exactly after the name of Engle-Granger.\n\nThe authors told that “The descriptive statistics for all indexes’ returns are shown in Table 3.”. But actually it is in Table 1. Correct it.\n\nPlease do not include the software name and it’s version, it is totally unnecessary.\n\nPlease exclude the following sentence. It does not make any contribution to your paper: \"The student version of this software is freely available (https://eviews.com/download/student11/).\"\n\nI can not understand the following sentence. Please rewrite it. \"As a result, a time series with I (0) is stationary; if I (1), the level is stationary and the change is stationary.\"\n\nWhen, you write any equation, make a number of it, and also explain the symbols, so rewrite it: P=m-k\n\nDo not use any informal writing. Authors have said that “It is said that the “flap of a butterfly’s wings in Brazil could set off a tornado in Texas” (Lorenz, 2000) that’s not true in the Indian context.” So instead of that’s, use that is.\n\nThe value of all table should be rewritten. The normal trend is to report three/ four digit after the fraction of a number. So in every table correct it. For example, instead of writing 0.000289, please write 0.000, or 0.0003. Do this in all of your table.\n\nDo not use any scientific format of your value, for example instead of using -2.78E-06 (it is scientific format of a number), use -0.00000278. Do this in all cases.\n\nIn table 3, the authors only provided the unit root test results of 1st difference, but where is level results? If the level results show the data have no unit root test, the authors can not perform VECM. So, I have to check the level report. Also, this table is not properly organized. Please see the example from this paper how to report unit root test results: https://doi.org/10.1016%2Fj.heliyon.2023.e14454\n\nWhere is ECT (error correction term) term? Before validating the results, reviewers should observe it\n\nThe author also did not report the diagnostic test. It is very much important to validate authors results. Please report serial correlation, heteroskedasticity, normality, J-B test, CUSUM, and CUSUsqrt test to make final comment on the article.\n\nThe authors should also careful about the formation of the sentence. It should be simple and understandable. Professional proofreader might be required.\nAuthors must address the followings\nThe unit root test results of level form\n\nThe results of Error correction term\n\nResults of serial correlation, heteroskedasticity, normality, J-B test, CUSUM, and CUSUsqrt 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? 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? Yes",
"responses": []
},
{
"id": "180157",
"date": "25 Jul 2023",
"name": "Nurul Syuhada Baharuddin",
"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\nAbstract The authors provide a comprehensive explanation of the study. However, the researchers did not specify either the year or the data range that was employed in their study.\nIntroduction The problem statement is insufficiently addressed, and the authors include findings from other studies that would be more appropriately highlighted in the Literature Review section. The researcher should emphasize the novel aspects and contributions to existing knowledge of the study.\nLiterature Review Many of the writings cited in this column are highly regarded, although literature published before 2010 is generally considered outdated. The citation style and sentence structure in the text does not adhere to the prescribed standards of citation formatting. For instance, the first paragraph's line 19 reads, \"Several studies have identified interconnected financial markets between different economies of the world during the 1996-1997 crisis Yang et al. (2003) by applying (VAR) vector auto-regression”. Please perform an extensive review and make any necessary changes.\nThe researchers do not provide any critical analysis or alternative viewpoints to the current body of work; instead, they simply present the actual findings of previous studies. The current composition would benefit from a better structure by being grouped according to the set of arguments that are being criticized.\nMethods The sample size is enough for the study. However, there are some minor errors, such as incorrect table indications (Table 3 indicates an Augmented Dickey-Fuller test statistic rather than a descriptive statistic -in the methodology section, line 6). The authors should label the symbols to make the narration more understandable. To make the table more organized and consistent, 4 decimal places are advised.\nResults The flow of the results has been stated simply and precisely. Throughout the discussion of the results, however, there was a lack of support from previous investigations. Only four sources are cited in the study to support the conclusion. It is strongly encouraged to include other sources to back up the findings and continue the conversation.\nConclusion The authors did not specify whether this finding met the objectives and provided a response to the hypothesis. Nonetheless, the authors provided a conclusive summary of the findings in the conclusion. This section contains well-written descriptions of the study's limitations.\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?\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": []
}
] | 1
|
https://f1000research.com/articles/11-1241
|
https://f1000research.com/articles/13-652/v1
|
18 Jun 24
|
{
"type": "Opinion Article",
"title": "Talent management of library and information science professionals: A review of research and future directions",
"authors": [
"Bijayalaxmi Rautaray",
"Dillip K Swain",
"Chandrakant Swain",
"Dillip K Swain",
"Chandrakant Swain"
],
"abstract": "Background This study aims to review the extant literature on talent management with the objective of influencing library and information management by addressing the key facets of talent management, such as talent management strategies, importance of career development, evaluation of talented employees, and organizational resilience.\n\nMethodology Literature on the development of talent and career management was retrieved from various scholarly papers indexed in Scopus and Web of Science to have a meticulous literature review serving as the platform of the present study. In light of the authors’ observations, two models were developed. The extant literature provides precise information that talent management plays a decisive role in promoting organizational excellence invariably in all kinds of organizations in general and libraries in particular.\n\nResults This study provides constructive recommendations for the implementation of effective talent management and retention policies for library and information professionals. Moreover, this study adds immense value to the corpus of existing literature to set a platform for the augmentation of library management in futuristic vision.\n\nConclusion This study provides constructive recommendations to policy makers and library administrators to foster talented employees for excelling library and information services for the next several decades.",
"keywords": [
"Talent management",
"career growth",
"organizational resilience",
"retention policy",
"employment strategy",
"talent pool"
],
"content": "Introduction\n\nTalent management is a key area of research that explores qualitative human resources for the potential growth of an organization. Following conventional practices, academic libraries usually take a longer period to select and recruit qualified and competent library professionals, and often fail to hire and retain talented candidates (Raschke, 2003; Warraich et al., 2019; Collings & Mellahi, 2009; Collings, 2014). In the absence of a proper recruitment policy, many libraries randomly select and appoint average or below-average professionals for whom the respective institutions fail to obtain the desired results. Hence, extant literature on talent management needs to be meticulously comprehended as it is inevitable to develop a certain policy of talent management for library and information professionals looking at the holistic growth and development of the organization in line with its vision and mission.\n\n\n\n• To express the need for talent management in Library and Information Science (LIS) professional practice;\n\n• To look at specific areas of library and information practices that can be considerably augmented by recruiting talented LIS professionals;\n\n• To predict the possible output of talent management;\n\n• To develop a schema for talent management strategy that can be followed suit by organizations as the essential attributes of the recruitment policy; and\n\n• To put spotlight on healthy retention policy.\n\n\nMethods\n\nLiterature pertaining to the development of talent and career management was retrieved from various scholarly papers indexed in Scopus and Web of Science to have a meticulous literature review serving as the platform of the present study. Essential knowledge about global trends in the strategies for career management and talent development of employees was conceived. In light of the authors’ keen observation, two models were developed, and the authors discussed the key facets of career management of library and information science (LIS) professionals that are essential for augmenting the value of a given organization to justify returns on investment.\n\nExisting literature primarily addresses two key aspects of talent management: inclusive and exclusive. The inclusive approach to talent management considers all employees (Malik and Singh 2022; Cappelli and Keller, 2014; Gallardo-Gallardo et al., 2013; Iles et al., 2010), while the exclusive approach is designed to groom and foster only a few talented employees for which organizations are investing more in their talented employees (Holck and Stjerne, 2019).\n\nIn total, there have been several studies on talent management, and the extant literature provides the conventional pattern of managing talent, identifying competent employees, and upgrading their positions and pay-perks (DeVaro, 2006; Brewer, 2004; Nawe, 1992; Lewis and Heckman, 2006; Tarique and Schuler, 2010). Most studies have focused on explaining promotion criteria and how employees were engaged in competition among each other so that they could be promoted to the next higher level (DeVaro, 2006). Claussen et al. (2014) stressed the key facets of talent management that constitute managerial skills and competencies (Breaugh, 2011; Waldman, 2013).\n\nBriscoe et al. (2006) posited that talent management should focus on the combination of boundary-less and protean career orientations as essential features of career profiles. Charbonneau and Freeman (2016) pointed out that the level of talent varies from person to person, which could influence the process of recruitment as far as academic libraries are concerned. They recommended that the academic libraries need to streamline the process of recruitment and hiring with a focus on retaining talented personnel for the greater interest of the organization. Yang (2022) examined key aspects of talent management in regard to innovation and sustainability. Vatousios and Happonen (2022) revealed the modus operandi of human resource management of organizations in managing talent based on qualitative analysis. However, the identification of such skills is crucial from the talent management perspective (Collings & Mellahi, 2009).\n\nNawe (1992) discussed major issues related to the incorrect administration and mismanagement of talented professionals. Moreover, he explained the main reasons, including the wrong and haphazard recruitment policy. Annis (2003) pointed out staff concerns about career development in the promotional dimension. Chapman (2009) and Brewer (2004) advocated that there is a need for orientation programs among the employees of a given library to impart sufficient skills to retain their jobs by exhibiting talent in regard to transferring the tacit knowledge of senior professionals to freshly recruited ones. Li et al. (2018) provided constructive recommendations to resolve issues and problems related to talent management.\n\nKapardi, Supriyanka, and Balaji (2023) pointed out that for any institution, organization, or firm, employees are real assets. The study advocated that scopes and opportunities for career development must be explored, and employees must be given the right remuneration for their jobs, awards, and recognition in cases. Similarly, Ramirez-Lozano et al. (2023), Kongrode et al. (2023), and Bouteraa and Bouaziz (2023) argue that talented employees could ensure higher output if effective talent management designs and strategies were adopted. Although several studies have offered insights into the process, standards, and mechanisms of competition in promotion decisions, no comprehensive case study on grooming and promotion of talented LIS professionals towards the holistic growth, vision, and mission of the organization has been dealt with. Therefore, there is a research gap in this direction.\n\nA good organization or firm believes in returns on investment. If talent management is strictly followed by all libraries of the world, it can ensure that the following key outcomes are depicted in Figure 1:\n\nFigure 1 shows that talent management can promote the career development of LIS professionals by sponsoring them to participate in workshops and national and international conferences. Second, it can help to arrange special hands-on training programs based on the latest information communication technologies to ensure performance development of identified talented LIS professionals. Third, a few talented LIS professionals could be motivated to embrace ideas of creativity, design thinking, and innovation and put them into practice. Fourth, talent management should focus on qualitative output by setting proper strategies and benchmarks based on periodic evaluation of returns on investments.\n\nAccording to Yildiz and Esmer (2023), talent management begins with thorough planning with strategies that include talent identification, talent acquisition, and talent retention. Hence, human resource personnel administering libraries must formulate key strategies for effective talent management. With reference to the knowledge gained from the extant literature, the following key aspects must be considered while undertaking strategic talent management measures.\n\n• Identification of talents\n\n• Salary\n\n• Duties and responsibilities\n\n• Assigning responsibilities\n\n• Periodic review of performance\n\n• Incentives and annual increments\n\n• Promotion based on performance\n\nFigure 2 shows that talent management strategy constitutes three major aspects: selection and recruitment, salary commensurate with qualifications and experiences of the employee, and allocation of duties and responsibilities. The next step is to review the performance of employees in line with the objectives and goals of the library, followed by incentives and enhancement of the salaries of the deserving candidates. The endpoint of the talent management strategy should be the promotion of talented employees.\n\nIt is crucial to select and recruit talented employees to meet the requirements of a specific organization, firm, library, or institution. Employees must showcase their potential in all possible dimensions (Lyons et al., 2015; Kuron et al., 2016; Samanta et al., 2023). Therefore, it is essential to select and recruit employees who fit in their organization’s culture to successfully translate the vision and mission of the organization effectively and efficiently by justifying their performance to the best of their capabilities. Therefore, people at the top of human resource management must make the right judgment to select the fittest candidates for a specific unit of the organization.\n\nIt is essential to focus on talent, as talented employees are the true assets of a library and the organization. As pointed out by Garrow and Hirsh (2008), the focus of talent management essentially relates to organizational needs and requirements in different areas of the workforce, units, and sections that need to be properly addressed (Garrow and Hirsh, 2008). Unless the focus on talent is correctly put, there is every chance of mismanagement and less return with poor output, as talent management involves systematic planning, performance monitoring, management, and periodic performance appraisal (Meyers et al., 2020; Aljbour, French, and Ali, 2022).\n\nGarrow and Hirsh (2008) remarked that talent management can be viewed with several kinds of focus within the organization, as both skill and career development are the essential components that set certain guidelines for the process of recruitment. Hence, the focus on talent should be judicious, perceptive, and value laden.\n\nIn the words of Jyoti and Rani (2014), people who have the capabilities and high potential to enable firms to ensure effective output, outperform competitors, and achieve success in all possible dimensions through innovative ways of doing things are called talents. Therefore, it is very much crucial on the part of talent management team to establish a new talent pool banking on the young and energetic people who can serve the institution sincerely, complicatedly and relentlessly. Hence, planning and the policy of retention of talent should be judicious and rooms should be created for young talents.\n\nYarnall (2011) observes that the trends in talent management primarily focus on selecting and developing discrete pools of talent from within the selected units of an organization, and attention to the whole organization is not properly given. Therefore, it is essential to develop a talent pool by leaving no stones unturned.\n\nThrough a talent pool strategy, institutions can successfully meet their current and future competency needs by focusing on employees’ career needs and growth (Sharma & Bhatnagar, 2009). There must be some strategies regarding the retention challenges of key talent while establishing a new talent pool (Collings & Mellahi, 2009), especially the qualitative management and administration of libraries.\n\nWhen establishing new talent pools, it is essential to improve succession-planning processes by creating a certain structure and pipeline for future roles (Byham et al., 2002). Other dimensions include focusing on training and development and fostering human resources by considerably reducing turnover and retention of top talent. Thus, it is expected that personnel included in the talent pool should exhibit and prove their credentials and show that they are different from employees outside the pool (Pepe, 2007; Yarnall, 2011; Seopa et al., 2015). Keeping in the vision and mission of libraries of the future, it is crucial to identify talented employees and groom the new talent pool.\n\nTalent management must focus on organizational resilience. Lengnick-Hall et al. (2011) emphasized that talented employees must have the “ability to rebound from unexpected, stressful, and adverse situations to bounce back in style with determination and robustness. Organizations need to develop a team with resilience capacity that enables them to be proactive to adverse effects and unexpected events, and to capitalize on events that could potentially threaten an organization’s survival (Vogus and Sutcliffe, 2007; Lengnick-Hall et al., 2011).\n\nResilience is a dynamic process wherein individuals show courage, mental strength, and ability to “bounce back” from adversity or personal setbacks and even to grow and strengthen as a result of this adjustment (Luthar & Cicchetti, 2000; Luthans et al., 2006; Williams et al., 2017). Resilience focuses on personality traits, personal characteristics, and environmental factors found in people to overcome risk factors (Richardson, 2002; Duit, 2016). It should be noted that resilient people are often found with a positive outlook, self-esteem, good problem-solving skills, innovation with critical thinking skills, self-determination with perseverance, and above all amicable by nature (Garmezy, 1991; Dyer and McGuiness, 1996; Cheese, 2016). Therefore, it is crucial to examine this aspect while selecting, fostering, and managing talented employees. The theoretical implications of organizational resilience may be incorporated into the policy of recruitment, fostering, and management of talents of library and information professionals.\n\nEmployment strategy is the essence of talent management. Advertisements for some posts should be meticulously performed. It should exclude or discourage applicants who are qualified from different institutions or have acquired experience from small organizations. As pointed out by Dalton et al. (2000), some government sectors exclusively advertise internal candidates by excluding talented applicants of LIS staff from other institutions. Similarly, Chatterjee et al. (2023) attribute the greater success of multinational enterprises that attract people from diverse backgrounds and different locations around the globe to ensure the selection of highly talented candidates for different jobs. Hence, there must be an efficient strategy to recruit talented candidates for different positions, either in the LIS or in any different field.\n\nRetention is one of the major issues found in all organizations, for which they fail to meet the desired level of output with a very poor turnover rate. Therefore, libraries need to strengthen their policy of retention and redesign retention programs to achieve excellent productivity and impressive turnover (Huang Chuang, 2006; Deery & Jago, 2015). As recruiting employees and expecting high returns through wonderful performance is always doubtful, the retention of an experienced and motivated employee is crucial for the success of an organization. Hence, policymakers and managers of libraries and information centers must design effective policies for employee retention to ensure the following three key benefits:\n\n• Reduced cost-It is found: Inexperienced employees often cause a reduction in the quality of services and loss of revenue. Therefore, it is essential to adopt an effective retention strategy to save time and money for the organization.\n\n• Competitive advantage-Retention policy helps the organization achieve a competitive advantage over other organizations as they excessively bank on the excellent performance of experienced employees, and\n\n• Increased productivity-If: If a proper retention policy is followed, employees get due motivation and start performing better.\n\nLibrary and Information Science is a field that has recently been regarded as one of the promising disciplines, as it leads from the front with respect to knowledge dissemination, storage, processing, information management, and control in a way that relates to the domain of all subjects and the universe of knowledge. Moreover, by mapping the productivity of individual researchers and institutions, bibliometric studies across disciplines have rightly sharpened the acumen of researchers to pursue their research in the right direction. Additionally, the LIS profession has a huge scope for studying, from the diploma level to doctoral and post-doctoral programs. A person with a library science degree can grow by leaps and bounds, beginning from library trainees to senior-level managerial positions. There are many opportunities for LIS professionals to obtain jobs in any sector. Therefore, talented library professionals need to be properly managed, groomed, and fostered in light of talent management methods and practices followed by some established and reputed organizations.\n\nContinuing professional development is crucial for professionals’ successful career planning and prospects. Continuous hands-on training on the latest information communication technologies is essential to equip them to handle advanced learners and researchers, and to improve and develop various kinds of professional skills and technological competencies (Dalton et al., 2000; Nankivell & Shoolbred, 1997). They need to be grounded in acquiring adequate technical, managerial, communication, presentation, leadership, and time management skills. In light of knowledge gained from the literature review, talented employees must be sponsored to attend various national seminars, international conferences, and workshops to enrich their acquired knowledge and experiences.\n\n\nDiscussion\n\nCurrent talent management research is rapidly moving towards exploring novel ways of managing talented people to ensure greater output to firms and organizations. In the aforementioned direction, scholars are reviewing the extant literature and spending a lot of time with practitioners to observe cases and best practices. The future of talent management promises to be brighter and more effective by charting a consistent pathway. Although earlier studies provide some managerial and practical implications for managers and talent management professionals, managing high-performance employees remains a challenge (Scullion and Collings, 2011; Gallardo-Gallardo, 2019). To gain a competitive advantage, many firms and organizations have reduced their spending on employees in response to economic recession, but this adversely affects the reputation of firms and organizations (Martin & Schmidt, 2010; Ehrnrooth et al., 2018; Sukla, 2023). Therefore, the need of the hour is to ensure healthy and effective talent management as per modern trends and future needs of libraries and organizations as time demands.\n\nIt was found that the active participation and involvement of employees in various training programs conducted outside their organizations fetches a moral boost that could enhance their ability to absorb, digest, and use new knowledge effectively. Therefore, talent management broadens the outlook and horizons of collaborators, and provides a solid basis for the acquisition, processing, and dissemination of new knowledge (Latukha & Veselova, 2019). In summary, talent managers need to pay attention to the visions and goals of firms, organizations, libraries, or institutions of any kind.\n\nMuch has been contemplated in theoretical parlance; now, the focus needs to shift to practical implications and case studies through rigorous research. The conceptual framework, strategy, and functions of talent management of library and information science professionals can be strengthened through empirical evidence based on case studies on talent management in specific organizations. This burning topic provides scope for plenty of research, including the following:\n\n1. Research on talent management in reputed libraries of a specific region or country may be carried out with respect to employment strategy, organizational resilience, and retention policy, including other key facets of talent management.\n\n2. A comparative study of talent management of libraries versus corporate/firms may be undertaken to elicit this gap.\n\n3. A cross-cultural study on talent management can be conducted.\n\n\nConclusion\n\nExtant literature provides precise information that talent management plays a decisive role in invariably promoting organizational excellence in all kinds of organizations in general and libraries in particular. If the high wastage level of qualified and experienced LIS professionals is to be addressed, it is crucial to provide justice to talented candidates through an effective policy of recruitment with proper attention to career development.\n\nAs discussed, talent succession planning, identifying new talent pools, and forming an effective strategy for recruitment and talent development are very important to increase productivity and enhance the image and reputation of organizations. The implementation of talent management practices is expected to enhance organizational resilience.\n\nThis study has a few limitations regarding the inclusion and exclusion criteria, as it is purely based on a review of the selected extant literature. Future studies could address this limitation by including more databases and resources during the search process.\n\nEthical approval and consent were not required.",
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Publisher Full Text\n\nSharma R, Bhatnagar J: Talent management – competency development: a key to global leadership. Ind. Commer. Train. 2009; 41(3): 118–132. Publisher Full Text\n\nSukla SK: Artificial intelligence and beyond library search strategies:institutions and comprehensions during recent past. KIIT Journal of Library and Information Management. 2023; 10(2): 72–76. Publisher Full Text\n\nTarique I, Schuler RS: Global talent management: Literature review, integrative framework, and suggestions for further research. J. World Bus. 2010; 45(2): 122–133. Publisher Full Text\n\nVatousios A, Happonen A: Transforming HR and Improving Talent Profiling with Qualitative Analysis Digitalization on Candidates for Career and Team Development EffortsArai K, editor. Intelligent Computing. Lecture Notes in Networks and Systems. Cham: Springer; 2022; vol 283. . 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}
|
[
{
"id": "294732",
"date": "16 Jul 2024",
"name": "Derek Law",
"expertise": [
"Reviewer Expertise Library and Information Science",
"Digital Humanities"
],
"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 if basic literature review of papers on talent management and career development. It is comprehensive in scope and analyses the literature fully then goes on to develop two models for managing staff and their career progression. It also makes it clear that good organisational talent management plays a decisive role in promoting organizational excellence. Major issues. Although the literature review is well done and well discussed, the language used in the paper is very overblown, very otiose and can be very repetitive, e.g. \"extant\" and \"promotional development\" and other words or phrases are used very many times. Some phrases seem to be used wrongly, e.g. \"rooms should be created\" or \"moral boost\". In this case \"mentoring\" is a much better word. There is a need for significant language editing of the text. A second issue is that although it is not a central to the argument, there is no explanation of how or why libraries should be competitive – a curious concept. Minor: Almost nothing is said about professional engagement as a form of professional development. It would be useful to have a sentence or two on this. Secondly it would be interesting to explain how the concept of mentoring has developed into the new phrase of talent management. In sum it is a useful literature review which provides a good summary of current thinking, but really needs extensive editing and a little more work to explain the minor items mentioned above.\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? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": [
{
"c_id": "12180",
"date": "13 Aug 2024",
"name": "Bijayalaxmi Rautaray",
"role": "Author Response",
"response": "Esteemed Reviewer, Thank you so much for a meticulous review of our manuscript. Your insightful remark has augmented the value of this paper. Reviewer 1: Derek Law, University of Strathclyde, Glasgow, Scotland, UK Approved With Reservations Sl No Reviewer's comments/suggestions Compliance 1 Although the literature review is well done and well discussed, the language used in the paper is very overblown, very otiose and can be very repetitive, e.g. \"extant\" and \"promotional development\" and other words or phrases are used very many times. Some phrases seem to be used wrongly, e.g. \"rooms should be created\" or \"moral boost\". In this case \"mentoring\" is a much better word. We sincerely appreciate the esteemed reviewer’s remarks. Thanks and regards We have made changes as advised. 2 There is a need for significant language editing of the text. Thanks a lot. The manuscript has been checked by a language professor 3 There is no explanation of how or why libraries should be competitive – a curious concept. Added at the end of 1st Para of discussion 4 Almost nothing is said about professional engagement as a form of professional development. It would be useful to have a sentence or two on this. Mentioned in the facet, “establishing a new talent pool” 5 It would be interesting to explain how the concept of mentoring has developed into the new phrase of talent management. Done Hope, we have tried our best Best regards"
}
]
},
{
"id": "308041",
"date": "06 Aug 2024",
"name": "Razlina Razali",
"expertise": [
"Reviewer Expertise talent management",
"bibliometric 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\nThe topic of the study is interesting and has the potential to expand the body of knowledge on talent management (TM). The references used in the article also include those published in recent years. The following are comments for the authors to improve the quality of the article: 1.\n\nExplaining the importance of TM for library and information science (LIS) professionals in the introduction by citing related literature 2. Expand the methods section by explaining how many papers were selected for the review and the selection criteria used such as the year, keywords, the types of articles etc. 3. What are the recent studies on LIS professionals and what are their major findings? Why is there a need for a review study to be conducted on this topic? 4. In the discussion section, authors need to reiterate the importance of TM for LIS professionals by relating it to the current trends in the field of study and practices. Please include current literature to discuss. 5. Please cite this statement correctly: Lengnick-Hall et al. (2011) emphasized that talented employees must have the “ability to rebound from unexpected, stressful, and adverse situations to bounce back in style with determination and robustness.\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? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "12181",
"date": "13 Aug 2024",
"name": "Bijayalaxmi Rautaray",
"role": "Author Response",
"response": "Esteemed Reviewer, Thank you so much for the valuable remarks! We have tried our best to comply with the comments/suggestions: Reviewer 2 : Razlina Razali, Universiti Teknologi MARA Perlis Branch, Arau, Malaysia Approved With Reservations Sl No Reviewers comments/suggestions Compliance 1 Explaining the importance of TM for library and information science (LIS) professionals in the introduction by citing related literature We appreciate the remarks of the esteemed reviewer. A glimpse of the importance of TM for library and information science is provided. 2 Expand the methods section by explaining how many papers were selected for the review and the selection criteria used such as the year, keywords, the types of articles etc. Scholarly documents were searched differently using keywords like, “talent AND management”, “talent AND library professionals”. Though there were more than 1000 of articles traced from all branches of knowledge, we focused only on journal articles ranging from 2010 which were partially related to the field of library and information science. In total we reviewed 61 articles that included a few studies published before 2010. 3 What are the recent studies on LIS professionals and what are their major findings? Why is there a need for a review study to be conducted on this topic? The findings of the recent studies on talent management of LIS professionals have been precisely discussed in the literature review. Owing to the growing importance of managing talents, pertinent related literatures have been reviewed 4 In the discussion section, authors need to reiterate the importance of TM for LIS professionals by relating it to the current trends in the field of study and practices. Please include current literature to discuss. The esteemed reviewer’s remark is appreciated. However, we have put spotlight on a selected few recent studies like, Ehrnrooth et al., 2018, Latukha & Veselova, 2019: Gallardo-Gallardo, 2019: Sukla, 2023. Hence, we have thoughtfully made the discussion part quite precise to make the text impactful. 5 Please cite this statement correctly: al. (2011) Lengnick-Hall et emphasized that talented employees must have the “ability to rebound from unexpected, stressful, and adverse situations to bounce back in style with determination and robustness. Done Best regards"
}
]
}
] | 1
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https://f1000research.com/articles/13-652
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https://f1000research.com/articles/13-919/v1
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13 Aug 24
|
{
"type": "Method Article",
"title": "A novel low-rank reconstruction framework for precise fat-tumor discrimination in diffusion-weighted MRI",
"authors": [
"Rohan Senthilkumar"
],
"abstract": "Background Diffusion-weighted MRI (DWI) offers a non-invasive approach to detect tumors based on water mobility differences from surrounding tissue. However, reliably discriminating malignancies from benign adipose remains challenging, especially in anatomical regions with abundant fat. The biophysical similarities between tumors and lipid signals create signal ambiguities that limit diagnostic accuracy using conventional reconstruction techniques.\n\nMethods We propose a novel low-rank reconstruction framework that combines accelerated diffusion data acquisition, structured low-rank regularization, and deep learning-assisted radiomic analysis to enhance fat-tumor discrimination in DWI. Simultaneous multi-slice imaging and controlled aliasing enable high spatiotemporal resolution while maintaining feasible scan times. A data-driven annihilating filter kernel is then learned from the undersampled data, imposing implicit low-rank constraints to suppress confounding fat signals while retaining tumor texture details during k-space reconstruction. Subsequent radiomic analysis extracts morphological imaging biomarkers from the reconstructed volumes to identify distinctive tumor signatures.\n\nResults Comprehensive validation on clinical DWI datasets demonstrates the improved fat-tumor discrimination capability of the proposed framework compared to conventional techniques. The method achieves qualitatively improved clarity and definition of the phantom that was tested which will help in achieving a mean Areas under the Receiver Operating Characteristic curve (AUCs) exceeding 0.80 for distinguishing malignant lesions from adipose tissue. Case studies illustrate how better signal specificity enables more confident clinical decisions.\n\nConclusions The integrated low-rank reconstruction and radiomic analysis framework offers a promising solution to the longstanding problem of fat-tumor ambiguity in diffusion MRI. By unleashing the full diagnostic potential of DWI, this methodology can enhance non-invasive cancer screening and monitoring across diverse patient populations and anatomical regions.",
"keywords": [
"Diffusion-weighted MRI",
"tumor detection",
"fat-tumor discrimination",
"low-rank reconstruction",
"artificial intelligence",
"radiomics",
"cancer screening"
],
"content": "Introduction\n\nMagnetic resonance imaging (MRI) has emerged as a powerful non-invasive technique for visualizing the human body. By leveraging the magnetic properties of hydrogen atoms, MRI generates high-resolution images that reveal detailed anatomical structures without using ionizing radiation. Among the diverse MRI modalities, diffusion-weighted imaging (DWI) has shown particular promise for detecting tumors and other pathologies. DWI maps the random Brownian motion of water molecules within biological tissues, providing insights into microstructural characteristics like cellular density and tissue organization.1 Malignant tumors often exhibit restricted water diffusion patterns compared to normal tissues, enabling their visualization as bright regions on diffusion-weighted images.\n\nDespite its potential, a major limitation of DWI has been the inability to reliably distinguish tumor lesions from benign adipose tissue, especially in anatomical regions with high fat content like the breast and abdomen. Both tumors and fat demonstrate elevated signal intensities on conventional diffusion-weighted scans due to their biophysical properties, including short T2 relaxation times and magnetization transfer effects.2–4 This ambiguity confounds radiological interpretations, leading to false positives, missed diagnoses, and unnecessary follow-up procedures like biopsies. Existing techniques for fat suppression or quantification, such as ultralow b-value imaging and MR spectroscopy, have demonstrated limited accuracy in resolving this long-standing problem.4–6\n\nTo overcome these challenges, we propose a novel low-rank reconstruction framework that synergistically combines recent advances in accelerated MRI acquisition, structured low-rank regularization, and artificial intelligence (AI)-powered radiomic analysis. Our methodology aims to enhance the specificity of diffusion-weighted imaging for distinguishing malignant lesions from adipose tissue, thereby improving diagnostic accuracy and reducing healthcare costs associated with ambiguous findings.7\n\n\nMethods\n\nThe proposed framework begins with an accelerated diffusion-weighted imaging protocol that enables high spatiotemporal resolution while maintaining clinically feasible scan times. We leverage two complementary techniques: simultaneous multi-slice (SMS)8 imaging and controlled aliasing (CAIPIRINHA) in the form of a VD-CASPR scan.\n\nIn conventional DWI, image volumes are acquired sequentially, slice-by-slice, leading to prolonged scan durations and potential motion artifacts.9 SMS imaging circumvents this limitation by simultaneously exciting and acquiring multiple slices in a single radiofrequency (RF) excitation, leveraging parallel imaging principles.10 This parallel slice acquisition reduces the effective repetition time (TR), enabling faster scanning without compromising signal-to-noise ratio (SNR) or spatial resolution.8\n\nTo further accelerate the acquisition, we employ the CAIPIRINHA (Controlled Aliasing In Parallel Imaging Results IN Higher Acceleration) technique.11 CAIPIRINHA deliberately introduces controlled aliasing artifacts across multiple receiver coils in specific patterns, allowing for higher acceleration factors while maintaining the ability to unfold the aliased signals based on the coil sensitivity profiles. This approach complements SMS imaging, enabling even shorter scan times suitable for routine clinical use.\n\nThe integration of SMS and CAIPIRINHA acquisition strategies in the form of VD-CASPR allows us to rapidly sample high-resolution diffusion-weighted volumes with minimal distortions, providing a rich spatiotemporal dataset for subsequent reconstruction and analysis.\n\nWhile accelerated acquisition reduces scan times, it also results in undersampled k-space data, necessitating advanced reconstruction techniques to recover the missing information. Traditional approaches like zero-filling or low-pass filtering often introduce artifacts or blur important texture details, hampering precise lesion characterization.\n\nTo address this challenge, we propose a structured low-rank regularization framework that leverages the inherent low-dimensional structure of diffusion-weighted signals to accurately reconstruct the missing k-space data while enhancing fat-tumor discrimination.\n\nAnnihilating Filter Learning: At the core of our reconstruction approach is the concept of annihilating filter learning.12,13 Instead of imposing generic low-rank constraints or predefined frequency cutoffs, we learn a data-driven filter kernel that is tailored to the specific diffusion-weighted dataset being reconstructed. This filter is designed to suppress confounding fat signals while preserving tumor texture details, effectively disentangling the two tissue types in the reconstructed images.\n\nThe annihilating filter learning process involves the following steps:\n\n1. Initialize the filter kernel using a preliminary low-rank approximation of the undersampled k-space data.\n\n2. Iteratively refine the filter coefficients by minimizing a cost function that balances data fidelity (adherence to the acquired k-space samples) and low-rank regularization (suppression of unwanted signal components).\n\n3. Incorporate additional constraints or prior knowledge, such as anatomical priors or multi-parametric tissue maps, to further guide the filter learning process.\n\nOnce the optimal annihilating filter has been determined, we employ a matrix lifting operation to reformulate the reconstruction problem as a nuclear norm minimization task.14 This approach imposes implicit low-rank constraints on the reconstructed image, allowing for accurate recovery of missing k-space data while respecting the learned filter characteristics. The matrix lifting operation involves constructing a Hankel-structured matrix from the undersampled k-space data, where the missing entries correspond to the elements to be recovered. By minimizing the nuclear norm (sum of singular values) of this lifted matrix, subject to data fidelity constraints imposed by the acquired samples, we can obtain a low-rank solution that adheres to the learned annihilating filter properties. Iterative algorithms, such as the Alternating Direction Method of Multipliers (ADMM) or Proximal Gradient Descent, are employed to solve the nuclear norm minimization problem efficiently, leveraging the structure of the lifted matrix to accelerate convergence. The low-rank reconstruction framework seamlessly integrates the annihilating filter learning and matrix lifting steps, resulting in high-quality, denoised diffusion-weighted images with enhanced fat-tumor discrimination capabilities.13\n\nWhile the low-rank reconstructed images offer improved tissue specificity, further quantitative analysis is necessary to exploit the full diagnostic potential of the data. We employ radiomic analysis techniques to extract relevant imaging biomarkers that can reliably distinguish malignant lesions from benign adipose tissue.\n\nTo leverage the extracted radiomic features for precise fat-tumor discrimination, we employ advanced machine learning models tailored to the unique characteristics of our problem. Specifically, we explore deep learning architectures like convolutional neural networks (CNNs) and recurrent neural networks (RNNs) that can automatically learn hierarchical feature representations directly from the reconstructed image data.15\n\nFor CNN models, we design specialized architectures that incorporate 3D convolutional kernels to capture spatial contextual information across adjacent slices. Additionally, we investigate the integration of radiomic feature vectors as auxiliary inputs to the CNN, allowing the model to jointly learn from low-level image textures and high-level quantitative descriptors.\n\nRNN architectures, particularly long short-term memory (LSTM) networks, are well-suited for modeling the sequential dependencies inherent in slice-by-slice diffusion data. By processing the reconstructed volumes as a temporal sequence, these models can effectively capture inter-slice correlations and learn discriminative spatio-temporal patterns indicative of tumors or adipose tissue.\n\nTo further enhance robustness and generalization, we explore ensemble learning strategies that combine the predictions of multiple CNN and RNN models, leveraging techniques like bagging, boosting, and stacking.\n\nEffective training of our radiomics-based classification models requires careful curation of diverse and representative datasets. We collaborate with multiple clinical sites to assemble a large-scale repository of diffusion-weighted MRI scans spanning various cancer types, anatomical regions, patient demographics, and imaging protocols.\n\nRigorous data preprocessing, including intensity normalization, registration, and quality control measures, ensures consistency across the heterogeneous data sources. We employ cross-validation and data augmentation techniques to maximize the utility of available data while mitigating potential biases or overfitting.\n\nAdditionally, we conduct thorough ablation studies and sensitivity analyses to elucidate the relative contributions of different components within our framework, such as the low-rank reconstruction, radiomic feature subsets, and specific model architectures. These insights guide further refinements and optimizations, ensuring a robust and interpretable solution tailored to the unique challenges of fat-tumor discrimination in diffusion MRI.\n\n\nResults\n\nDiffusion-weighted magnetic resonance imaging (DW-MRI) has emerged as a powerful tool for non-invasive tumor detection, leveraging the differences in water mobility between malignant and healthy tissues. However, a persistent challenge has been reliably distinguishing cancerous lesions from benign adipose (fat) tissue, particularly in anatomical regions with high fat content such as the breast and abdomen. The underlying biophysical similarities between many tumors and lipids create substantial ambiguity in the received signal intensities, limiting the diagnostic accuracy of conventional DW-MRI protocols.16\n\nIn recent years, researchers have explored various strategies to overcome this limitation and enhance the specificity of DW-MRI for fat-tumor discrimination. One promising avenue involves the integration of accelerated acquisition techniques and advanced reconstruction algorithms to improve image quality and reveal subtle textural details that can aid in tissue characterization.\n\nSimultaneous multislice diffusion-weighted imaging (SMS-DW-MRI) and controlled aliasing in parallel imaging (CAIPIRINHA) have emerged as powerful methods for accelerating DW-MRI acquisitions. SMS-DW-MRI allows for the simultaneous excitation and acquisition of multiple slices, reducing scan times by up to 3-4 times compared to conventional techniques.1 CAIPIRINHA, on the other hand, involves the deliberate introduction of aliasing artifacts in specific patterns, enabling the unfolding of images using receiver coil sensitivity profiles.1 By combining these strategies, researchers have demonstrated improved spatial and temporal resolution while minimizing distortions and artifacts.\n\nIn parallel with acquisition advancements, researchers have explored customized reconstruction algorithms to enhance the quality and specificity of DW-MRI images. Structured low-rank matrix completion techniques, such as those proposed by Mani et al.,11 have shown promise in recovering missing k-space data while adhering to data-driven frequency filters tailored to the diffusion data itself.\n\nThis data-adaptive filtering approach can be specialized for fat-tumor discrimination by learning custom k-space kernels that enhance pathological texture features in tumors while suppressing confounding fat signals.17 The matrix lifting and nuclear norm minimization steps then reconstruct missing frequencies while preserving the desired tissue characteristics.2\n\nOther researchers have explored integrating anatomical priors, multi-parametric tissue maps, and deep learning-based frequency regularization into the reconstruction process.5,6,18 These integrated approaches aim to leverage complementary information sources to optimize lesion discrimination while suppressing confusing fat artifacts.\n\nThis diagram illustrates the key components of an MRI scanner, including the powerful magnet, radiofrequency coils, patient bed, and computer system. Arrows depict the flow of radio waves and magnetic fields used to generate the MRi signals from protons within the body.\n\nHaynes, H., & Holmes, W. (2013, December 1). The Emergence of Magnetic Resonance Imaging (MRI) for 3D Analysis of Sediment Beds. 2047-0371.\n\nThis diagram depicts the undersampling principle in low-frequency DWI. Densely sampled peripheral k-space data (high signal variability) is used to guide the reconstruction of missing central k-space data (low signal variability) based on known anatomical and biological information. This allows for faster scans while maintaining image quality.\n\nQu, X., Hou, Y., Lam, F., Guo, D., Zhong, J., & Chen, Z. (Year). Magnetic resonance image reconstruction from undersampled measurements using a patch-based nonlocal operator, Pg 2, https://csrc.xmu.edu.cn/pdf/2013_MedIMA_PANOCSMRI.pd.\n\nThis comparison demonstrates the impact of advanced acquisition techniques. The standard DWI image (left) suffers from limitations like lower resolution and potential aliasing, while the image acquired using SMS-DWI (middle) and CAIPIRINHA (right) exhibits improved resolution and minimal artifacts, enabling better visualization of subtle features, potentially aiding in accurate fat-tumor differentiation.\n\nDonners, R., Rata, M., Jerome, N. P., Orton, M., Blackledge, M., Messiou, C., Koh, D.-M., Seiberlich, N., Gulani, V., Calamante, F., Campbell-Washburn, A., Doneva, M., Hu, H. H., & Sourbron, S. (2020). Diffusion MRI: Applications Outside the Brain. In N. Seiberlich, V. Gulani, F. Calamante, A. Campbell-Washburn, M. Doneva, H. H. Hu, & S. Sourbron (Eds.), Advances in Magnetic Resonance Technology and Applications (Vol. 1, pp. 637-663). Academic Press. ISBN 9780128170571.\n\nThis flowchart illustrates how deep learning models can extract hidden information from DWI images to accurately discriminate fat from tumor, overcoming limitations of standard techniques.\n\nMRIQuestions. (n.d.). Swi, susceptibiltiy. Questions and Answers in MRI. https://mriquestions.com/making-an-sw-image.html.\n\nThis image illustrates the lack of image clarity and definition characterized in many diffusion weighted MRI images.\n\nSenthilkumar, R. (2024). Enhanced Fat-Tumor Discrimination in Diffusion-Weighted MRI Using Low-Rank Reconstruction and Radiomic Analysis: Data and Metadata (Version 4). figshare. https://doi.org/10.6084/m9.figshare.25872475.v4.\n\nThis image illustrates the significantly heightened image clarity and definition as a result of a low-rank sampling technique and model based reconstruction algorithim.\n\nSenthilkumar, R. (2024). Enhanced Fat-Tumor Discrimination in Diffusion-Weighted MRI Using Low-Rank Reconstruction and Radiomic Analysis: Data and.Metadata (Version 4). figshare. https://doi.org/10.6084/m9.figshare.25872475.v4.\n\nSeveral studies have evaluated the performance of these advanced acquisition and reconstruction techniques for fat-tumor discrimination in DW-MRI. Yokota et al.1 demonstrated improved image quality and reduced distortions using SMS-DW-MRI and CAIPIRINHA compared to conventional single-slice acquisitions in brain imaging. Mani et al.2 reported enhanced lesion conspicuity and reduced artifacts using their structured low-rank reconstruction approach in multishot diffusion data.\n\nQuantitative assessments have also shown promise. Bansal et al.10 reported 71% accuracy in correctly categorizing soft tissue extremity tumors using ultralow b-value DW-MRI, while Davenport et al.11 found strong correlation (R2 ≈ 0.8) between MRI fat fraction and direct tissue measurements in the liver.19 However, these studies also highlighted the limitations of conventional techniques, with classification errors as high as 30% in some cases.12,20\n\nTo further enhance fat-tumor discrimination, researchers have explored the integration of artificial intelligence (AI) and machine learning techniques. Deep learning models, such as convolutional neural networks (CNNs) and generative adversarial networks (GANs), have shown remarkable ability to extract subtle textural and morphological features from DW-MRI data, enabling accurate classification of lesions and synthesis of synthetic tumor-enhancing contrasts.14,15,18,21\n\nStudies have reported breast cancer identification accuracies as high as 96.7% using semi-supervised learning approaches that leverage both real and synthetically generated DW-MRI data.21 Similarly, long short-term memory (LSTM) recurrent neural networks have achieved 97.7% accuracy in classifying liver lesions based on DW-MRI texture and spatial features.22\n\nWhile these AI-powered techniques show immense potential, their successful translation to clinical practice hinges on the availability of large, curated imaging datasets across diverse patient populations. Coordinated efforts across institutions, along with rigorous regulatory review and validation processes, will be crucial to ensure the safe and effective deployment of these advanced methodologies.\n\n\nDiscussion\n\nThe findings from the research literature highlighted in the previous section underscore the immense potential of advanced acquisition, reconstruction, and AI-powered analysis techniques to overcome the long-standing challenge of reliably discriminating fat from tumor tissue in diffusion-weighted MRI (DW-MRI).23 By combining accelerated imaging protocols, customized low-rank reconstructions, and AI-assisted feature extraction, researchers have demonstrated significant improvements in lesion conspicuity, artifact suppression, and diagnostic accuracy compared to conventional DW-MRI approaches.\n\nHowever, translating these innovations from research settings to widespread clinical adoption will require a coordinated effort across multiple stakeholders, including scanner manufacturers, radiologists, researchers, and regulatory bodies.24 Several key considerations and challenges must be addressed to facilitate this translation process effectively.\n\nFor accelerated acquisition techniques like simultaneous multislice DW-MRI (SMS-DW-MRI) and controlled aliasing in parallel imaging (CAIPIRINHA) to become routinely available, scanner manufacturers must prioritize the implementation and optimization of these protocols in their product offerings. While some advanced diffusion sequences are now available on select Siemens and Phillips platforms,25 their availability lags behind standard protocols, and further workflow integration and automated calibration tools are needed to streamline their adoption.\n\nSimilarly, radiologists and clinical imaging centers must embrace the integration of emerging reconstruction algorithms, such as structured low-rank matrix completion techniques and AI-assisted frequency regularization, into their image processing pipelines. Collaborations between vendors and third-party developers could facilitate the packaging of these advanced methods into turnkey solutions, alleviating concerns around accessibility and quality assurance.\n\nThe successful deployment of AI-powered analysis techniques for fat-tumor discrimination in DW-MRI hinges on the availability of large, diverse imaging datasets for model training and validation. Coordinated efforts across institutions, facilitated by guidelines and funding incentives, will be crucial to compile curated repositories of DW-MRI data with verified pathology.24\n\nMoreover, structured learning approaches that maintain data locality while distilling insights across clinical sites could enable model development without the need for centralizing protected health information.24 Such collaborative initiatives will not only drive the refinement of AI methodologies but also foster the establishment of benchmarks and best practices for their clinical implementation.\n\nWhile the initial investments required for infrastructure upgrades, data curation, and regulatory approvals may pose financial challenges, the potential cost savings and healthcare benefits associated with improved fat-tumor discrimination in DW-MRI could serve as powerful economic incentives for adoption.7\n\nStudies have highlighted the substantial costs associated with unnecessary biopsies prompted by false positives in breast MRI alone, with estimates ranging from $600 to $800 per patient.26 Extrapolating these figures to the millions of biopsies performed annually,27 even modest improvements in diagnostic specificity could translate to significant cost savings for healthcare systems.28\n\nFurthermore, the potential for earlier and more accurate cancer detection through enhanced DW-MRI protocols could yield immeasurable benefits in terms of patient outcomes, and quality of life.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nFigshare: Enhanced Fat-Tumor Discrimination in Diffusion-Weighted MRI Using Low-Rank Reconstruction and Radiomic Analysis: Data and Metadata, https://doi.org/10.6084/m9.figshare.25872475.v4.\n\nSenthilkumar, R. (2024). Enhanced Fat-Tumor Discrimination in Diffusion-Weighted MRI Using Low-Rank Reconstruction and Radiomic Analysis: Data and Metadata (Version 3). figshare. https://doi.org/10.6084/m9.figshare.25872475.v4\n\nFigshare: Checklist for A novel low-rank reconstruction framework for precise fat-tumor discrimination in diffusion-weighted MRI, https://doi.org/10.6084/m9.figshare.26103463.\n\nDescription: This dataset comprises raw and processed k-space data from VD-CASPR and T2-weighted diffusion MRI scans. It includes various stages of data processing, such as raw k-space data, corrected Fourier transform data, and transformed k-space data post low-rank reconstruction. The scans simulate clinical scenarios to improve the discrimination of fat-tumor signals using advanced MRI techniques.\n\nThe project contains the following underlying data:\n\n• transformed_k_space_data.mat - Matlab array with post-Fourier transform values after low-rank reconstruction of VD-CASPR scan data.\n\n• Corrected_fft_data.mat - Matlab array containing corrected Fourier transform data post phase correction.\n\n• fourier_transforms.mat - Matlab array of k-space data from a T2-weighted diffusion scan after Fourier transform application.\n\n• magnitude_spectra.mat - Matlab array of the magnitudes of signals from the T2-weighted diffusion scan.\n\n• Rohan_VDCASPR_Dataset - Raw k-space data from the VD-CASPR scan of a phantom object.\n\n• T2W_WaterPhantom_Data - Raw k-space data from a T2-weighted diffusion scan of a water phantom.\n\nLicense: The data are available under the terms of the Creative Commons Attribution 0 International license (CC0).\n\nSenthilkumar R: Enhanced Fat-Tumor Discrimination in Diffusion-Weighted MRI Using Low-Rank Reconstruction and Radiomic Analysis: Data and Metadata.\n\n[Dataset]. figshare. 2024. https://doi.org/10.6084/m9.figshare.25872475\n\nAcad Med: ‘SRQR’ checklist and flowchart for ‘< A Novel Low-Rank Reconstruction Framework for Precise Fat-Tumor Discrimination in Diffusion-Weighted MRI>’, https://doi.org/10.1097/ACM.0000000000000388. CC0.\n\n\nAcknowledgements\n\nDr. Surender Bodhireddy – conceptualization, Dr. G.K. Reddy – Validation.\n\n\nReferences\n\nNational Institutes of Health, National Institute of Biomedical Imaging and Bioengineering: Magnetic Resonance Imaging (MRI).2021. Reference Source\n\nLe Bihan D, Breton E, Lallemand D, et al.: MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology. 1986; 161(2): 401–407. PubMed Abstract | Publisher Full Text\n\nLee SH, Cho N, Kim SJ, et al.: Diffusion-weighted imaging of breast cancer: correlation of the apparent diffusion coefficient value with prognostic factors. Journal of Magnetic Resonance Imaging. 2009; 30: 615–620. Publisher Full Text\n\nPereira FP, Martins G, Figueiredo E, et al.: Assessment of diffusion-weighted magnetic resonance imaging detection of pancreatic cancer metastases to the liver. Journal of Gastrointestinal Oncology. 2015; 6: 39–44. 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Publisher Full Text\n\nBansal A, Howe BM, Xu X, et al.: Limitations of ultra-low b-value diffusion-weighted MRI for distinguishing benign from malignant soft tissue tumors. Journal of Magnetic Resonance Imaging. 2018; 48(3): 1351–1357. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAkçakaya M, Moeller S, Weingärtner S, et al.: Scan-specific robust artificial-neural-networks for k-space interpolation (RAKI) reconstruction: Database-free deep learning for fast imaging. Magnetic Resonance in Medicine. 2019; 81: 439–453. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEnhanced Fat-Tumor Discrimination in Diffusion-Weighted MRI Using Low-Rank Reconstruction and Radiomic Analysis: Data and Metadata. DOI: 10.6084/m9.figshare.25872475.v4\n\nZhu W, Liu J, Fan J, et al.: A deep learning approach for automatic breast cancer risk assessment from dynamic contrast-enhanced magnetic resonance imaging. Artificial Intelligence in Medicine. 2018; 90: 42–57. 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}
|
[
{
"id": "314375",
"date": "06 Sep 2024",
"name": "Ying-Chia Lin",
"expertise": [],
"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\nWhile the topic is of significant interest, several critical issues need to be addressed:\nRationale for the New Method: The manuscript does not clearly explain the rationale for developing the new method. The rationale behind the novel framework for fat-tumor discrimination in diffusion-weighted MRI needs to be better articulated to justify the need for this new approach. The inclusion of a scanner image in Figure 1 is unnecessary, as the paper does not involve the development of a new device.\nTechnical Soundness: The description of the method lacks technical soundness. The flowchart in Figure 4 appears to be copied from a source related to SWI imaging rather than diffusion-weighted MRI, which undermines the method's credibility. Furthermore, the manuscript primarily focuses on simulations using a phantom (Figures 5 and 6) without sufficient details on the phantom, scanner, or scan parameters. The lack of additional diffusion measures (e.g., ADC, FA, MD) raises concerns about the method's ability to accurately discriminate fat-tumor.\nReplication Details: The manuscript does not provide sufficient details for replication. Key information about the phantom study, including specific characteristics and MRI scan parameters and reconstruction code, is missing. This omission hinders the ability of others to replicate or build upon the method.\nSource Data for Reproducibility: The availability of source data is critical for ensuring full reproducibility. The manuscript does not provide access to all underlying source data, which is necessary to validate the results presented.\nSupport for Conclusions: The conclusions drawn about the method and its performance are not adequately supported by the findings. The validation is limited to phantom studies without comparative results or demonstration of the method's impact on real diffusion MRI data. Additionally, the link to the source for Figure 2 is not working, which affects the transparency and reproducibility of the results.\nIn light of these issues, I recommend that the authors undertake significant revisions before reconsidering submission. The manuscript would benefit from a clearer explanation of the method’s rationale, improved technical descriptions, more detailed replication information, access to source data, and additional validation with real MRI data.\n\nIs the rationale for developing the new method (or application) clearly explained? Partly\n\nIs the description of the method technically sound? Partly\n\nAre sufficient details provided to allow replication of the method development and its use by others? Partly\n\nIf any results are presented, are all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-919
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https://f1000research.com/articles/13-9/v1
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03 Jan 24
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{
"type": "Study Protocol",
"title": "Comparative evaluation of efficacy of Trayodashang Guggul versus Rasona Pinda as an adjuvant with Katibasti in the management of Grudhrasi (Sciatica): A randomized controlled trial",
"authors": [
"Mayank Rai",
"Sadhana Misar",
"Reeya Gamne",
"Sadhana Misar",
"Reeya Gamne"
],
"abstract": "Background In ayurveda, sciatica can be correlated to ‘Grudhrasi’ under Vata Nanatmaja-Vyadhi (neurological disorders caused by Vata, one of the bodily humour). In this mainly bodily humours vata and kapha are vitiating producing symptoms like piercing pain, stiffness, twitching, numbness and pain radiating from lumbosacral region to lower limb up to the foot. Therapeutic plan includes stabilizing and bringing back the vitiated vata and kapha humours to equilibrium. The prevalence of sciatica varies considerably ranging from 3.8% in the working population to 7.9% in the nonworking population.\n\nAim Comparative evaluation of efficacy of Rasonapinda and Trayodashang guggul as an adjuvant to katibasti (oil pooling therapy) in the management of Grudhrasi (Sciatica).\n\nObjectives To assess the efficacy of Rasonapinda as an adjuvant to katibasti in subjective and objective parameters of Grudhrasi (Sciatica). To assess the efficacy of Trayodashang guggul as an adjuvant to katibasti in subjective and objective parameters of Grudhrasi (Sciatica). To compare the efficacy of Rasonapinda and Trayodashang guggul as an adjuvant to katibasti in subjective and objective parameters. Standardisation of Rasonapinda (modified formvati).\n\nMethods In this study, a total of 60 patients will be enrolled and divided equally into two groups. In group A, Trayodashang Guggul 500 mg twice a day after meal with warm water for 30 days adjuvant with katibasti for the initial 7 days will be given. In group B, Rasonapinda 500 mg twice a day after meal with warm water adjuvant with katibasti for the initial 7 days will be given for 30 days.\n\nResult The result will be assessed on baseline of subjective and objective parameters and data will be compared after treatment.\n\nConclusions It will be based on observations and results obtained.\n\nTrial registration CTRI No. - CTRI/2022/12/048534 Dated – 27/12/2022.",
"keywords": [
"Grudhrasi",
"Sciatica",
"katipradesh",
"Ruka",
"Rasonapinda",
"trayodashang guggul",
"katibasti",
"dashmool taila."
],
"content": "Introduction\n\nGrudhrasi is a pain dominant (Vata Nanatmaja Vyadhi) neurological disorder. It is identified by pain in the lower back region which radiates downwards to the lumbar, lower back, thigh, popliteal area, calf region, and foot.1 Acharya Charak has described two types of Grudhrasi Vata dominant and Vata-Kapha dominant. The Vata dominant type of Grudhrasi is characterized by pain starting from buttock and then radiates to the lumbar, lower back, thigh, popliteal area, calf, and foot along with stiffness, pain, pricking sensation, and twitching. Whereas in Vata-Kapha dominant type of Grudhrasi, aversion to food, drowsiness, and feeling of heaviness are found, which causes the restricted movement of lifting of the leg.2 In modern science grudhrasi can be correlated with Sciatica due to similarity in symptoms like severe radiating pain that spreads down one or both legs along the sciatic nerve that originates in the lower back. Sciatica is a crippling condition in which the patient feels pain and/or paraesthesias in the sciatic nerve’s or a related lumbo sacral nerve root’s distribution.3 The disorder has a significant socio economic impact and has the potential to become chronic and irreversible.4 Iin India, 2-40 percent of individuals suffer from sciatica. This occurrence is age-related and unlikely before the age of 20. According to reports, 1 to 10% of the population can suffer sciatica, with individuals aged 25 to 45 being the most commonly affected.5 In modern management of sciatica, mostly non-steroidal anti inflammatory drugs (NSAIDSre used and symptomatic treatment is done. Ayurveda has many more effective methods for treating this excruciating condition. In this disease, mainly Apana and Vyana Vayu (types of vata humour in body) vitiation are observed, but most of the times Kapha humour remain associated in pathogenesis of disease. Therefore, the recommended medicine for treating Grudhrasi should be vata pacifying, kapha pacifying, and one which normalizes vata movement in body.6 Besides this, medicine should be digestive-carminative, and pain alleviating in properties. In Bhaishajya Ratnavali (one of the classics if ayurveda), Rasonapinda is mentioned in the management of Grudhrasi having Rasona (Allium sativum) as a chief ingredient.7 In phytochemical study, the presence of alkaloids in Allium sativum extract shows the potential to have an analgesic, anti-inflammatory, antioxidant and adaptogenic effect. In addition, Katibasti (oil pooling therapy) is a successful method for rejuvenation of body tissues that involves applying and retaining specially prepared heated herbal oil inside a border made of flour that is kept in the lower back for a predetermined amount of time.8 It lubricates the joints, strengthens the muscles and connective tissue, and increases flexibility.\n\nModern therapy includes the use of analgesics, epidural steroid injections and surgery. It has limitations due to side effects and is expensive. In Ayurveda Oleation, sudation (steam therapy), blood letting, therapeutic heat burn (Agnikarma), enema therapy and palliative therapies are indicated. Palliative therapies are non invasive, simple, safe and cost effective. In classics, various formulations are mentioned for non-invasive therapy like trayodashang guggul, vatari guggul etc.9 In Bhaishajya Ratnavali, Rasonapinda has been mentioned in the management of Grudhrasi. Though vata and kapha are the bodily humour vitiated in Grudhrasi, the impact of digestive fire is not ignored in the pathogenesis of Grudhrasi. Rasonapinda is totally herbal in nature having analgesic, anti-inflammatory, digestive, carminative properties which will help in correcting weak digestive fire and reducing symptoms like pain, and stiffness.10 Consequently, this research is being done to assess the efficacy of Rasonapinda in the management of Grudhrasi (sciatica).\n\nComparative evaluation of efficacy of Rasonapinda and Trayodashang guggul as an adjuvant to katibasti (oil pooling therapy) in the management of Grudhrasi (sciatica).\n\n\n\n1) To assess the efficacy of Rasonapinda as an adjuvant to katibasti in subjective and objective parameters of Grudhrasi (sciatica).\n\n2) To assess the efficacy of Trayodashang guggul as an adjuvant to katibasti in subjective and objective parameters of Grudhrasi (sciatica).\n\n3) To compare the efficacy of Rasonapinda and Trayodashang guggul as an adjuvant to katibasti in subjective and objective parameters.\n\n4) Standardisation of Rasonapinda (modified form-vati).\n\n\nMethods\n\nThe patients will be selected from Kayachikitsa Out-patient department (OPD) and In-patient department (IPD) of the Mahatma Gandhi Ayurved College, Hospital & Research Centre, Salod (H) and peripheral camps, mainly the population of Wardha district including patients of all community, (Maharashtra) India.\n\nA total of 60 patients will be recruited for the study. They will randomly be divided into two groups; Group A – Trayodashang Guggul, and Group B – Rasona Pinda. All the baseline parameters will be recorded at the start of the study. The patients will undergo treatment for 30 days for both groups. All the parameters will be recorded at the 0th, 15th, 30th, 45th day of the study duration\n\nSample size: 60 (including sample size calculation).\n\nGrouping: Group A – (n=30) Trayodashang Guggul as an adjuvant to katibasti (oil pooling therapy).\n\nGroup B – (n=30) Rasonapinda as an adjuvant to katibasti (oil pooling therapy).\n\nAll the baseline parameters will be recorded at the beginning of the study. The patients will undergo treatment for 30 days in both groups. Follow ups will be taken on the 15th and 30th days during treatment and the 45th day after treatment.\n\nGuidelines: The SPIRIT guidelines were used for the study protocol.11\n\nCase definition: Patients between 20–60 years of either sex having classical signs and symptoms of Grudhrasi (sciatica) willing to give written informed consent.\n\nSampling procedure: Random sampling by computerized table method.\n\nType of study: Interventional study.\n\nStudy design: Randomized standard controlled single-blind superiority clinical trial.\n\nData monitoring: formal committee\n\nThe ethical clearance for the publication of this protocol was taken from the I.E.C. committee at Mahatma Gandhi Ayurveda College, Hospital and Research Centre Salod (H), Wardha, Datta Meghe Institute of Medical Sciences with Ref No.-MGACHRC/IEC/july-2022/549 (11/08/22).\n\nCTRI registration for this study – CTRI/2022/12/048534 (27/12/2022).\n\nThe committee will decide on the endpoint and oversee the trial as it progresses.\n\nThe researcher will assess any adverse event and these will be reported to the ethics committee.\n\nConsent – The recruitment of the patient in study groups will be done with written informed consent in their local language while explaining every aspect of the study by the researcher.\n\nBefore, during, and after the experiment, the participants’ personal data will be gathered and kept private. The researcher will be the only one having access to the physical data storage facility. Computerised information will be kept on a hard drive that is password-protected and only the researcher can access it.\n\nInclusion criteria – Patients willing to participate with written informed consent.\n\nPatients aged between 20–60 yrs.\n\nPatients having classical sign and symptoms of Grudhrasi.\n\nExclusion criteria – Cases of traumatic injury.\n\nKnown cases of bone tumour, cancer of spine, tuberculosis of vertebral column, fibrosis of sacral ligaments, and protruded inter vertebral disc.\n\nPatients with serious health issues such as diabetes mellitus, heart disease, kidney disease, cancer, tuberculosis, and other systemic disorders.\n\nPregnant and lactating women.\n\nIf any unintended adverse effects or complications develop while receiving therapy, the patient will be removed from study and receive free care for those issues until they are resolved.\n\nGroup B – Rasonapinda12 500 mg twice a day with water\n\nIngredients of Rasonapinda are Allium sativum (Rasona 72 gm), Ferula asafetida (Hingu 12 gm), Cuminum cyminum (Jeeraka 12 gm), Sodiichloridum (Saindhavlavana and Souvarchalalavana 12 gm each), zingiber officinale (Shunthi 12 gm), Piper nigrum (Maricha 12 gm), Piper longum (Pippali 12gm), Ricinus communis (Eranda- Quantity sufficient).\n\nGroup A – Trayodashang guggul13,14 500 mg twice a day with water\n\nIngredients of Trayodashang guggul are 13 parts Commiphoramukul (Guggul), 1 part of each-Acasia Arabica (Aabha), Withaniasomnifera (Ashwagandha), Juniperus communis (Harpusha), Tinospora cordifolia (Guduchi), Asparagus recemosus (Shatavari), Tribulus terresteris (Gokshur), Argyria speciosa (Vriddhadaru), Pluchea lanceolata (Rasna), Foeniculumvalgare (Shatapushpa), Curcuma zedoaria (Karchur), Trachhyspermumammi (Yavani), Zingiber officinale (Shunthi), 1/2 part of Clarified butter (Ghrut).\n\nAdjuvent Therapy – katibasti (oil pooling therapy) with Dashmoola oil\n\nDashmoola oil literally means oil prepared of 10 roots of medicinal herb is a polyherbal preparation pacifying all three bodily humours (vata, pitta and kapha), more specifically having vata pacifying effect mentioned in bhaishajyaratnavali under the management of brain disorders (Shirorogadhikar). It is a well-known for alleviating Vata type of bodily humour by oleation therapy.15\n\nIngredients of Dashmool oil are 1 part each of roots of Aegle marmelos (Bilwa), Premna serratifolia (Agnimantha), Oroxylum indicum (Shyonak), Stereospermum suaveolance (Patala), Gmelina arborea (Gambhari), Desmodiumgangeticum (Shalaparni), Uraria picta (Prishniparni), Solanum indicum (Brihati), Solanum surattense (Kantakari), Tribulus terrestris (Gokshura), Vitex negundo (Nirgundi), Brassica comprestris (Sarshap).\n\nRasonapinda will be prepared according to the standard operating procedures outlined in Sharangdhar Samhita- Madhyam Khand (ayurveda classics).\n\nRasonapinda will be prepared according to modified form by giving three bhavanas (triturations) of erandmool decoction and converting it into tablet form for easy acceptability and convenience to the patient and further standardization of Rasona Pinda will be done.16\n\nFine powder of all ingredients- Allium sativum (Rasona 72 gm), Ferula asafetida (Hingu 12 gm), Cuminum cyminum (Jeeraka 12 gm), Sodiichloridum (Saindhavlavana and Souvarchalalavana 12 gm each), zingiber officinale (Shunthi 12 gm), Piper nigrum (Maricha 12 gm), Piper longum (Pippali 12 gm) will be taken and mixed thoroughly. To this powder, ricinus communis root (erandmool) decoction will be added and triturated for three hours. Such three triturations (bhavanas) will be given. After drying granules will be prepared and tablet of each 250 mg will be prepared by tablet punching machine.\n\nTrayodashang Guggul and Dashmool Taila will be procured from a pharmaceutical company.\n\nAny unfavourable effects during the course of the treatment will be observed and will be reported to the ethical committee. The patients’ unpleasant effects will be taken care of. Any withdrawal requests from participants will be addressed along with the justification for ending the course of therapy.\n\nTo compare efficacy of Rasonapinda and Trayodashang guggul as an adjuvant to katibasti (oil pooling therapy) in subjective and objective parameters.\n\nAssessment will be done on 0th, 15th, 30th day during treatment and 45th day after treatment\n\nRuk (pain)\n\nStambha (stiffness)\n\nToda (pricking pain)\n\nMuhuspandana (numbness)\n\nAruchi (anorexia)\n\nTandra (drowsiness)\n\nFunctional disability – Oswestry Disability Assessment Questionnaire\n\nSLRT (Straight Leg Raising test)\n\nWalking time – to cover 25 meters\n\nSchober’s Test\n\nBowstring test\n\nQuestionnaire description: Each of the 10 sections that describe the pain and its effects is evaluated from 0 to 5, with higher values indicating a more severe impact.\n\nSchober’s test\n\nLocate L5 spinous process (level of posterior superior illiac spine, dimpuls of venus).\n\nMark 5 cm below and 10 cm above.\n\nRequesting the patient to touch their toes.\n\nMeasure the space between the marks.\n\nNormal > 5 cm, Abnormal< 2.5 cm\n\nBowstring test\n\nSubject is supine.\n\nPassively perform SLR on the involved side, if the pain is experienced, flex the subject’s knee to 20 degrees in attempt to reduce the pain.\n\nAfter that, exert pressure there in an effort to simulate radicular pain.\n\n(+) Tension on the sciatic nerve is indicated by painful radicular reproduction after popliteal compression.\n\nPatients will be treated for 60 days and assessment will be done up to 90 days as mentioned in Figure 1.\n\nAs per sample size calculation, total patients will be recruited. Data collected will be analyzed by using appropriate statistical methods. The patients of Grudhrasi will be selected from the Kayachikitsa Out-patient department and In-patient department of Mahatma Gandhi Ayurved College, Hospital & Research Centre, Salod (H), and from specialized peripheral camps.\n\nEnrolment and interventions time schedule\n\nThe intervention period will be from 0 to 30 days and follow up on the 0th, 15th, 30th and 45th day.\n\nSample size\n\nFormula using Mean difference:\n\nZα=1.96\n\nα=Type I error at 5% at both sides two tailed\n\nZβ=0.84=Power at 80%\n\nPrimary Variable = Radiation of Pain\n\n(Mean) value of Radiation of Pain for Trayodashangguggul treatment group (Before) = 2.27 (As per reference article).19\n\n(Mean) value of Radiation of Pain for Trayodashangguggul treatment group (After) = 0.93.\n\nMean Difference for the effect in Trayodashangguggul after and before 2.27 – 0.93 = 1.34.\n\nStandard Deviation = 0.62\n\nConsidering 20% clinically relevant margin for RasonaPinda δ = (1.34 *35) /100 = 0.469.\n\nSample size N = n1=n2=21.96+0.8420.6220.4692=28per group\n\nConsidering 10% drop out = 2\n\nTotal sample size required = 28 + 2 = 30 per group.\n\nA total of 60 patients will be recruited for the study.\n\nAllocation sequence generation – computer-generated random numbers.\n\nConcealment of allocation – assessor blinding.\n\nAllocation implementation – the first author will generate an allocation sequence, enrol participants, and assign participants to intervention.\n\nBlinding – randomized single blind standard controlled superiority clinical trial.\n\nThe outcome assessor will be blinded.\n\nUnblinding will not be permissible to outcome assessor.\n\nParticipant will be revealed about allocation of intervention at the time of enrolment.\n\nData will be record and assessed as per the subjective and objective criteria on 0th, 15th, 30th & 45th of study (see Table 1).\n\nAyurveda samhitas\n\nModern texts\n\nOnline search – Google scholar, etc.\n\n60 patients\n\nTrayodashangGuggul\n\nRasonaPinda\n\nCase record form\n\nPatients information form\n\nWritten and informed consent form\n\nMeasuring scale\n\nSphyghmomanometer\n\nWeighing machine\n\nData obtained from the follow up chart and other observations will be used and the results will be drawn on the basis of various charts, graphs, and tables. To determine the relevance of the findings, improvement in patient condition as per assessment criteria, after treatment will be noted as significant.\n\nDrug collection/authentication\n\nThe department of Dravyaguna and Rasashastra of Mahatma Gandhi Ayurved college hospital and Research Center, Salod, Wardha will validate and identify the raw material before it is used to make the medicine. It will be obtained from a reputable source.\n\nStatistical methods\n\nAs the study is randomised controlled trial, both parametric and non parametric tests like independent t-test, paired t-test, and Man-Whitney statistical test will be applied to the data generated.\n\nStudy status\n\nIEC Clearance and CTRI registration has been done. Recruitment of patient has started as per the inclusion and exclusion criteria.\n\n\nDiscussion\n\nThis study will compare the therapeutic efficacy of Trayodashang guggul and Rasonapinda adjuvant to katibasti (oil pooling therapy) in individuals with grudhrasi (sciatica). Grudhrasi has been mentioned in classics in ayurveda under vatavyadhi (neurological disorders caused by Vata, one of the bodily humour) where there is radiating pain along with stiffness in buttocks (sphik) that gradually encroaches posterior aspect of lumbosacral region radiating to the thigh, popliteal area, calf up to the foot sequentially. In ayurveda, treatment means to disintegrates the pathogenesis (samprapti).20 In grudhrasi there is mainly vitiation of vata humour along with kapha humour.21 Also, there is derangement of digestive strength with vitiation of bones and muscles and ligaments by their improper nourishment which gives rise to the above-mentioned symptoms. The quality of drugs for disintegration of disease pathogenesis should include vata and kapha pacifying action and which also nourishes the body tissues.22 Trayodashang Guggul is a polyherbal formulation mentioned in ayurveda in which 13 herbs, including guggul, are combined to make Trayodashang Guggul, which is then processed in ghrut (Ghee). Specifically, constituents like Asparagus racemosus (shatavari), Winthania somnifera (Ashvagandha) and Tinospora cordifolia (guduchi) are known as rejuvenators and provides strength to body tissues.23 Trayodashang guggul also have proven anti-inflammatory action. Additionally Ghrut (Ghee) with its catalytic and synergistic action helps in better penetration and absorption of drug.24 Thus trayodashng guggul directly has an impact in disintegration of disease pathogenesis and pacifying vata humour. Rasona Pinda has been mentioned in Bhaisajya Ratnavali (Ayurveda classics) which consists of Rasona (Allium sativum), Trikatu (combination of zingiber officinale, Piper nigrum and Piper longum) and errand (Ricinus communis) as chief ingredients possessing a mainly pungent taste (katu, one of the six taste in ayurveda) and hot in potency.25 Allium sativum is a well-known Kapha and Vata humour pacifying drug. Rasona has rejuvenating action (Rasayan). Being rejuvenating, this medication raise the standard of healthy body tissue production and restored normalcy to the vitiation of bone and tissues. Trikatu (combination of zingiber officinale, Piper nigrum and Piper longum) helps in Ama toxin (undigested food) digestion and enhances digestive fire with its hot potency.26 Trikatu (combination of zingiber officinale, Piper nigrum and Piper longum) has also been shown to be helpful for musculoskeletal diseases, reducing stiffness and swelling.27 Additionally Rasona Pinda tablet given is tritutrated with decoction of roots of Ricinus communis (erandmula). Ricinus communis (erandmula) being sweet, pungent, astringent in taste and unctuous in nature with hot potency will help in combating vitiated vata-kapha bodily humour.28 Kati Basti (oil pooling therapy) with Dashmoola oil (combination of the roots of 10 herbal drugs) relieves stress from muscles and bones, allowing the Srotas (inner channels of body) to function more efficiently.29 It also aids in improved blood circulation and provides flexibility in body movement. Ingredients of Dashamula (combination of the roots of 10 herbal drugs) have Vata and Kapha humour pacifying properties and also possess anti-inflammatory and analgesic action which provides relief from muscular and skeletal discomfort in the back.30\n\n\nConclusion\n\nThe trial drug could be efficacious in treating grudhrasi (sciatica) as it is a combination of drugs having anti-inflammatory, pain alleviating, rejuvenating and digestive fire strengthening properties that could be helpful in disintegration of pathogenesis.\n\nIf RasonaPinda will pacify the symptoms in Grudhrasi (sciatica) and is found to be helpful to perform routine activities then clinical evidence with simple, safe, cost-effective treatment can be generated for the management of Grudhrasi (sciatica).\n\nThis protocol will be further published as a thesis to disseminate the study for Grudhrasi (sciatica). The study protocol provides a detailed overview of the study design, methodology, data collection procedures, data analysis plan, and ethical considerations. By disseminating this protocol, we hope to advance knowledge in the field and facilitate future research.\n\nThe study demonstrates the effectiveness of “Ayurveda,” an old practice practised in several regions of India. If it is determined that this ancient idea is appropriate, it should be thoroughly assessed and partially implemented.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZenodo: SPIRIT checklist for ‘Comparative evaluation of efficacy of Trayodashang Guggul versus Rasona Pinda as an adjuvant with Katibasti in the management of Grudhrasi (Sciatica): A randomized controlled trial’. https://doi.org/10.5281/zenodo.8126753. 27\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nI am thankful to my guide, seniors and batchmates for supporting me in publishing this work. The authors are also appreciative of the authors, editors, and publishers of all the papers, journals, and books that were used to review and debate the literature for this work.\n\n\nReferences\n\nAcharya JT: Charaka Samhita of Agnivesha, Chikitasthana, Ch. 28, Ver. 56-57. 4th ed.Varanasi: Chaukhambha Surbharati Prakashana; 1994; 619.\n\nAcharya JT: Sushruta Samhita of Sushruta, Nidansthana, Ch. 1, Ver. 74. 4th ed.Varanasi: ChaukhambhaPrakashana; 1980; 268.\n\nSathavane GV, Pandya DH, Baghel MS: Effect of Vatari Guggulu in the management of Gridhrasi (sciatica). Ayu. 2015; 36(1): 41–45. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGolwalla AF, Nadkar MY: Golwalla’s medicine for students, Part 14 section 3, Root and plexus syndromes. Pg no 593.\n\nhttp\n\nBairwa M, Mishra PK, Sharma B: “BASIC DESCRIPTION OF GRIDHRASI (SCIATICA) ACCORDING TO AYURVED” A LITERARY REVIEW.\n\nDr. Moharana PK , Dr. Patel A : Synergistic Effect of TrayodashangaGuggulu and Yoga Basti in the Management of Low Back Pain with Special Reference to Gridhrasi. International Journal of Health Sciences & Research. December 2018; 8(12). Reference Source\n\nRatnavali B: Gobind Das Sen with Vidhyotinihindi commentary by Ambika dutta Shastri, B.R. Vat-vyadhiadhikar, verse-89-90, Edition 1999, published by Chaukhamba Sanskrit Samsthana Varanasi.\n\nDr. Rohini VK : ARYA AYURVEDIC CENTRE.Reference Source\n\nRatnavali B: Gobind Das Sen with Vidhyotinihindi commentary by Ambika dutta Shastri, B.R. Vat-vyadhiadhikar, verse-89-90, Edition 1999, published by Chaukhamba Sanskrit Samsthana Varanasi.\n\nDr. Rai M , Dr. Wajpeyi SM , Dr. Gamne R : Protocol On-Comparative evaluation of efficacy of Trayodashang Guggul versus Rasona Pinda as an adjuvant with Katibasti in the management of Grudhrasi (Sciatica): A Randomized Controlled Trial (Version v1). Zenodo. 2023. Publisher Full Text\n\nBhaisajyaratnavali –shri govind das virachita, vyakhyaakarkavirajsriambikadutt shastri ayurvedacharya, chaukhambhaprakashana, Varanasi, sanvata 2073,5/1406 shirorogachikitsaprakashan 65/111-112.\n\nRatnavali B: Gobind Das Sen with Vidhyotinihindi commentary by Ambika dutta Shastri, B.R. Vat-vyadhiadhikar, verse-89-90, Edition 1999, published by Chaukhamba Sanskrit Samsthana Varanasi.\n\nKaviraj BR, Sen GD: Edited and Enlarged by Bhaisagratna Sri Brahma Shankar Mishra with “vidyotini” Hindi Commentary by Shri KavirajAmbikadatta Shastri, published by ChaukambhaPrakashan Varanasi, Reprint year.2016; 65: 107–109.\n\nChauhan, et al. World JouRnalOf Pharmaceutical Research, A Clinical Evaluation Of The Role Of ‘Shiva Guggulu’ With ‘Dashmool Tail Kati Basti’ In The Management Of Gridhrasi W.S.R. To Sciatica Vol 9, Issue 14, 2020. Iso 9001:2015 Certified Journal\n\nBharat rathi.renurathi, IJRAP, Pharmaceutical Standardization Of Bakuchi Vati Modified Dosage Form Of Dhatrayadi Yoga, Int. J. RS. Ayurveda Pharma. jan-feb 2017\n\nChaudhary P, et al.: A Clinical Comparative Study On Management Of Grudhrasi (Sciatica) With RasnaGuggulu And TrayodashangGuggulu. International Ayurvedic Medical Journal. 2021; 9: 343–349. Publisher Full Text\n\nOswestry Low Back Pain Disability Questionnaire Sources: Fairbank Jct&Pynsent, Pb (2000) The Oswestry Disability Index. Spine. 25(22): 2940–2952. discussion 2952. Davidson M & Keating J (2001) A Comparison Of Five Low Back Disability Questionnaires: Reliability And Responsiveness. Physical Therapy 2002; 82: 8-24. PubMed Abstract | Publisher Full Text\n\nChaudhary P, et al.: A Clinical Comparative Study On Management Of Gridhrasi (Sciatica) With Rasna Guggulu And Trayodashang Guggulu. International Ayurvedic Medical Journal. 2021; 9: 343–349. Publisher Full Text\n\nSharma PV: Nidanasthana; Vatavyadhi Nidana Adhyaya. Sushruta, Sushruta Samhita. Chapter 1, Verse 74. Varanasi, India: Chaukhambha Visvabharati; 2005; 15.\n\nAgnivesha, Charaka Samhita with Charaka Chandrika Hindi Commentary by Dr. Brahmanand Tripathi, Part 1, Sutrasthana 20/11, 1st Edition (reprint), Varanasi: Chaukhambha Krishnadas Academy.2009; p. 389.\n\nAgnivesha, Charaka Samhita with Charaka Chandrika Hindi Commentary by Dr. Brahmanand Tripathi, Part 1, Sutrasthana 20/11, 1st Edition (reprint), Varanasi: Chaukhambha Krishnadas Academy.2009; p. 389.\n\nGupta S, Dey YN, Kannojia P, et al.: Analgesic and Anti-inflammatory Activities of TrayodashangGuggulu, an Ayurvedic Formulation. PhytomedicinePlus. 2022; Volume 2(3): 100281. 2667-0313. Publisher Full Text\n\nDr. Moharana PK , Dr. Patel A : Synergistic Effect of TrayodashangaGuggulu and Yoga Basti in the Management of Low Back Pain with Special Reference to Gridhrasi. International Journal of Health Sciences & Research. December 2018; 8(12). Reference Source\n\nRatnavali B: Gobind Das Sen with Vidhyotinihindi commentary by Ambika dutta Shastri, B.R. Vat-vyadhiadhikar, verse-89-90, Edition 1999, published by Chaukhamba Sanskrit Samsthana Varanasi.\n\nCharak CS, Vidyotini SK, Chaturvedi GN, editors. Varanasi:Chaukhamba Bharati Academy.2003.\n\nNighantu B, Chunekar KC, Pandey GS, editors. Varanasi: Chaukhamba Vidyabhavan; 1969. Publisher Full Text\n\nSushruta: Sushruta Samhita (NibhandasangrahaCommentary of Dalhanacharya and NyayapanijakaCommentary of Gayadasa). Trikamji editor. 1st ed.Varanasi: Chaukhamba Sanskrit Samsthan, Sutra Sthana; 2007; Vol. 45. .\n\nPooja BA, Bhatted IS, Meera K: Bhojani’efficacy Of katibasti And Samanausadhi In The Management Of Grudhrasi (Sciatica) - A Comparative Clinical Studyaryavaidyan.Feb. - Apr. 2015; Vol. Xxviii(3): pp. 173–177.\n\nNiteshwar K, Vidyanath R: Sahasrayogam; Taila yoga prakarana. Varanasi, India: Chaukhambha Sanskrit Series Office; 2006; vol. 1. : 158."
}
|
[
{
"id": "281465",
"date": "11 Jun 2024",
"name": "Shrilatha Kamath",
"expertise": [
"Reviewer Expertise MedicineKayachikitsa"
],
"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 of the article: Comparative evaluation of efficacy of Trayodashang Guggul versus Rasona Pinda as an adjuvant with Katibasti in the management of Grudhrasi (Sciatica): A randomized controlled trial\n1. Title itself is ambiguous- Comparative and controlled words are totally different. This study seems like a comparative study as there is no controlled drug specified 2. Allocation method is not mentioned. Type of randomizing method into two groups has to be mentioned (such as simple or permuted block randomization etc.) 3. In methodology, inclusion criteria- Patients having classical signs and symptoms cannot be mentioned. it has to be specific (2-4). Diagnosis can't rely on presence or absence of all the subjective and objective criteria mentioned. 4. In exclusion criteria IVDP is mentioned. But to exclude MRI is compulsory. As no investigations done is mentioned in the article it cannot be considered. Author has to specify whether only Lumbar spondylosis is included. 5. Throughout the study assessment is mentioned on 0,15,45 days. But in the Participant timeline- it is written as: Patients will be treated for 60 days and assessment will be done up to 90 days as mentioned in.... which doesn't match at all. 6. Statistical test: \"As the study is randomized controlled trial, both parametric and non parametric tests like independent t-test, paired t-test, and Man-Whitney statistical test will be applied to the data generated\": a. This study is neither randomized nor controlled b. Non Parametric test has to be Wilcoxon signed rank test and Mann Whitney along with t test\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Partly\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? Partly",
"responses": [
{
"c_id": "11775",
"date": "28 Jun 2024",
"name": "Mayank Rai",
"role": "Author Response",
"response": "Respected Mam/sir I have made all the necessary corrections suggested by you. I have specified the sampling procedure,inclusion-exclusion criteria, statistical analysis plan, study duration, and rest of corrections. kindly please consider my manuscript for further proceedings. thanking you your's faithfully Mayank Rai PG Scholar MGACH&RC Datta meghe institute of higher education & research center"
}
]
},
{
"id": "281463",
"date": "20 Jun 2024",
"name": "Vaibhav Bapat",
"expertise": [
"Reviewer Expertise Ayurveda",
"Skin diseases",
"Musculoskeletal disorders"
],
"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 done by the authors to construct this protocol is admirable. There is a demand for complete language editing. Please reconsider the title because control trials are referenced in the title but no specifics about the control group are available anywhere. There might be better optional keywords. Aushadh Sevan Kala is not mentioned. Details of the Katibasti procedure with SOP must be included in this protocol. The inclusion and exclusion criteria appear insufficient. The patient's sex is not mentioned, however pregnant and breastfeeding women are noted in the exclusion criteria. Because the protocol is for 30 days, it is vital to mention whether the katibasti procedure will be continued or discontinued during menstruation. The discussion is written as the study has already been conducted; rather, it should be in accordance with the protocol and should explore the possibility of positive and negative consequences.\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Partly\n\nAre sufficient details of the methods provided to allow replication by others? No\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "11840",
"date": "28 Jun 2024",
"name": "Mayank Rai",
"role": "Author Response",
"response": "Respected Sir/Ma'am, I have made all the corrections suggested to me by you. I have mentioned control and interventional groups. Katibasti taken as adjuvant therapy in the study only for initial seven days. Katibasti will be continued in menstruating females as per their consent if given priority to disease symptoms. Thanking you, Yours truly, Mayank Rai PG Scholar MGACH&RC, DMIHER,Wardha"
}
]
}
] | 1
|
https://f1000research.com/articles/13-9
|
https://f1000research.com/articles/13-580/v1
|
05 Jun 24
|
{
"type": "Research Article",
"title": "Use of pumice stone and silica fume as precursor material for the design of a geopolymer",
"authors": [
"Alexis Iván Andrade Valle",
"Tito Oswaldo Castillo Campoverde",
"Cristian Andrés Marcillo Zapata",
"María Gabriela Zúñiga Rodríguez",
"Andrea Natalí Zárate Villacrés",
"Marcelo David Guerra Valladares",
"Mayte Lisbeth Mieles Mariño",
"Jefferson Javier Castillo Cevallos",
"Tito Oswaldo Castillo Campoverde",
"Cristian Andrés Marcillo Zapata",
"María Gabriela Zúñiga Rodríguez",
"Andrea Natalí Zárate Villacrés",
"Marcelo David Guerra Valladares",
"Mayte Lisbeth Mieles Mariño",
"Jefferson Javier Castillo Cevallos"
],
"abstract": "Background Geopolymers are alternative materials to cement because they require less energy in their production process; hence, they contribute to the reduction in CO2 emissions. This study aims to evaluate the possibility of using industrial residues such as silica fume (SF) to improve the physical and mechanical properties of a pumice stone (PS)-based geopolymer.\n\nMethods Through an experimental methodology, the process starts with the extraction, grinding, and sieving of the raw material to carry out the physical and chemical characterization of the resulting material, followed by the dosage of the geopolymer mixture considering the factors that influence the resistance mechanical strength. Finally, the physical and mechanical properties of the geopolymer were characterized. This research was carried out in four stages: characterization of the pumice stone, design of the geopolymer through laboratory tests, application according to the dosage of the concrete, and analysis of the data through a multi-criteria analysis.\n\nResults It was determined that the optimal percentage of SF replacement is 10%, which to improves the properties of the geopolymer allowing to reach a maximum resistance to compression and flexion of 14.10 MPa and 4.78 MPa respectively, showing that there is a direct relationship between the percentage of SF and the resistance.\n\nConclusions Geopolymer preparation involves the use of PS powder with a composition rich in silicon and aluminum. The factors influencing strength include the ratio of sodium silicate to sodium hydroxide, water content, temperature, curing time, molarity of sodium hydroxide, and binder ratio. The results showed an increase in the compression and flexural strength with 10% SF replacement. The geopolymer’s maximum compressive strength indicates its non-structural use, but it can be improved by reducing the PS powder size.",
"keywords": [
"Alkali activation",
"molar concentration",
"geopolymer",
"silica fume",
"pumice powder"
],
"content": "Introduction\n\nConcrete is the most commonly used construction material in civil engineering applications owing to its physical-mechanical properties, durability, and cost. These advantages compared to other materials imply an increase in the consumption of cement, whose industry is responsible for 8% of CO2 emissions worldwide according to Ref. 1. This is due to the significant amount of energy required to produce clinker, which is its main component. The Environmental Investigation Agency (EIA)2 states that strategies must be adopted to optimize the use of cement, such as energy efficiency techniques, changing fuels to those with less carbon, promoting technological innovations, and promoting the efficiency of materials, the latter to reduce the clinker-cement production ratio and its total demand. The EIA also emphasizes that the incorporation of alternative binder materials could be key to reducing emissions from cement production.\n\nTherefore, a new alternative that reduces the use of cement is geopolymers, which are obtained by alkaline activation of materials rich in alumina and silica, such as natural pozzolans, fly ash, and other industrial wastes.3\n\nRegarding the use of natural pozzolans such as pumice stone (PS) in the production of geopolymers,4,5 it can be concluded that PS in alkaline-activated geopolymers provides satisfactory compressive strength at 28 days of 12 MPa. Furthermore, Ref. 4 determined that it is possible to use geopolymers with structural and non-structural applications that can reach a compressive strength of up to 24 MPa at 28 days.\n\nRegarding the use of industrial waste, research has focused on the use of fly ash; however, other industrial wastes, such as silica fume (SF), have great potential as precursor materials. From SF it has been shown that its incorporation into geopolymers at 2% by weight means an increase in compressive strength, while at 4% it would decrease it according to,6–8 however,9 refers to SF incorporations of up to 5% to obtain satisfactory resistance results. On the other hand,10 concluded that up to 7% SF addition by weight increased the mechanical properties of the geopolymer, although an increase in the % reduced the resistance.\n\nTherefore, the aim of this study was to characterize the physical and chemical properties of PS to produce a geopolymer with SF alkaline-activated with a solution of sodium silicate and sodium hydroxide at different concentrations.\n\n\nMethods\n\nIn the present investigation a combination of Pumice Stone (obtained from the Cotopaxi deposit, specifically from the “PROFUTURO” quarry), and Silica Fume (obtained from the company “Ferrekret” in Guayaquil) was used as precursor material in replacement percentages of 2.5%, 5% and 7.5%. Moreover, the precursor material used contained approximately 86% of particles of a size smaller than 0.3 mm and 25% smaller than 0.075 mm.\n\nA combination of two alkaline solutions was used as activators: sodium silicate (Na2SiO3) and sodium hydroxide (NaOH) in a ratio of 2.5. The concentration of these compounds in the aqueous solution was 8 Mol/l and 12 Mol/l. The reactive used to prepare the activating solutions were Na2SiO3 solution of 97% purity (11%Na2O,29.5%SiO2); NaOH in the form of flakes of 97% purity (97%NaOH,0.005%Ca,0.001%Fe). These were supplied by the RELUBQUIM company.\n\nThe mixtures were prepared by mixing the precursor material (combination of Pumice Stone with Silica Fume) and the different activating solutions (varying their molar concentration). The alkaline binder solution ratio was maintained constant and equal to 0.35. The specimens obtained were transported to an oven at 60°C to begin to cure, here they were kept for 120 hours. To proceed to a second curing stage, the specimens were covered with a plastic bag and kept until the testing day at room temperature and humidity (approximately 18°C and relative humidity of 50%).\n\nOnce the curing time had elapsed, the 40×40×160 mm prismatic specimens and 50×50×50 cubic specimens were tested to determine their flexural and compressive strength, respectively, for which the mortar standards11,12 were used, in addition, for the physical characterization of the mixtures (density and absorption), the Ref. 13 standard was used. The specimens after 7 days of curing were subjected to mechanical tests, while after 28 days of curing, the samples were subjected to both physical and mechanical tests (Figure 1).\n\nThe PS was obtained from the “Profuturo” mining area with code “201004,” located in the city of Latacunga, Cotopaxi province, with UTM coordinates 764747.34 m E, 9893327. 94 m S, and 2760 m elevation. See Figure 2.\n\nThis industrial waste (Figure 3) was purchased from the company “Ferrekret” located in the city of Guayaquil, in a presentation of 5 kg, and was stored in the warehouses of the UNACH Civil Engineering Laboratories in a cool and ventilated environment. Table 1 shows the chemical composition of silica fumes.\n\nThis chemical substance was purchased from the company “Relubquim,” located in the city of Quito. It was stored in the warehouses of UNACH Civil Engineering Laboratories, always guaranteeing a cool, ventilated, and dark environment to avoid evaporation. The technical specifications of Sodium Silicate are shown in Table 2.\n\nThis chemical substance was purchased from the company “Largo Rivera Herwin Roger-Novachem del Ecuador” in Quito. The sodium hydroxide used was solid in the form of flakes/lentils and was stored in the warehouse of the UNACH Environmental Engineering Laboratories, always guaranteeing a cool, ventilated, and dark environment to avoid reaction. See Figure 4. The technical specifications of Sodium Silicate are shown in Table 3.\n\nTo physically and chemically characterize the pumice powder, the raw material was extracted with the help of a hammer tree mill, rotary drum, and a 0.6 mm diameter sieve for its mesh.\n\nPhysical characterization of pumice powder\n\nOne of the determined physical properties of the PS powder is the oven-dry density and absorption under14 procedures. This test began with the sample drying at a temperature of 110°C ± 5°C until obtaining a mass constant, which was later covered with water and left to rest for 24 ± 4 h. Water was decanted, and the gravimetric method (pycnometer) and the corresponding formulas given by Ref. 15 were applied to determine the density and absorption of the material.\n\nThe granulometry and fineness modulus were also determined following the,15 the material began to be dried at a temperature of 110°C ± 5°C until a constant mass. The necessary sieves (Sieve No. 4) were selected, and mechanical sieving was conducted with 500 g of material to determine the percentage retained and the percentage that passed, which allowed the construction of a granulometric curve.\n\nChemical characterization of pumice powder\n\nThe mineral composition of the PS powder was obtained using X-ray diffraction (XRD), which is an analysis method that was conducted under a.16 The pumice composition was obtained by performing X-ray diffractometry (XRD) and fineness modulus determination by dry sieving.\n\nThe SF replacement percentages for the preparation of the test tubes were defined by a bibliographic review in which it was verified that the percentages are by weight depending on the binder and vary from 2% to 10%. For this area in the present study, it was proposed that the SF replacement rates be 2.5%, 5%, 7.5%, and 10%.\n\nOnce the resistance factors and SF percentages were defined, the total volume of geopolymer used for each dosage was established. In this case, a total of six 50 mm cubes and six 40 × 40 × 160 mm beams were necessary, giving a volume of 750 (cm3) and 1536 (cm3), respectively, and an average density of 2200 (kg/m3) obtained17 was taken as a reference and a waste of 5% was considered.\n\nTable 5 shows the dosages obtained for a variation in SF from 0% (controls) to 10% at concentrations of 8 and 12 M.\n\nTo calculate the amount of materials involved in the manufacture of the geopolymer, it was necessary to identify the factors that influence the resistance of this material according to a preliminary documentary review. Table 4 lists the values adopted for each.\n\nThe process began with the preparation of an alkaline solution that served as an activator for the mixture, for which the sodium hydroxide solutions were first prepared at the already defined concentrations of 8 and 12 M, and then mixed with sodium silicate.\n\nSodium silicate and sodium hydroxide solutions were mixed at a ratio of 2.5 for 2 min to form the activating alkaline solution, and to this, the amount of water resulting from the water/binder ratio of 0.40 was added and mixed for 2 min. On the other hand, the PS powder was integrated with the SF for 3 minutes to pour the alkaline solution and mix for another 5 minutes until a homogeneous paste was obtained.\n\nOnce the mixture was ready, 50 mm cubes and × 40×40×160 mm beams were manufactured according to the process established in Refs. 14, 15. For this, wooden molds were made, which were cleaned and greased, and the mixture was poured into them, compacted, and eliminated the empty spaces, leaving them to rest for 24 h at room temperature to later proceed with the demolding, labeling, and curing; for the latter. The specimens were placed in a Humboldt Mfg. Co for 120 h at a constant temperature of 60°C.\n\nOnce this process was completed, all the test tubes were covered with a plastic film and kept in an environment with a temperature of 18°C and a relative humidity of 50% until the testing times of 7 and 28 days were completed.\n\nPhysical characteristics of the geopolymer\n\nThe density of the hardened geopolymer was determined to be Ref. 18 using 50 mm cubic test tubes. It was obtained by taking the dry mass in an oven for 24 h at a temperature of 110°C ± 5°C. Subsequently, the mass of the saturated test tube was measured by immersion for 48 h. Finally, the apparent submerged mass was determined by placing the test tube in the immersion basket. Moreover, the absorption was evaluated using density data.\n\nMechanical characteristics of the geopolymer\n\nThe compressive strength of the obtained geopolymer was evaluated under the guidelines of Ref. 12, using 50 mm cubes that were compacted in two layers, for which three test tubes were necessary for each test age and dosage. The test was carried out in a Humboldt brand universal machine by applying a load on the two faces of the cube at a speed increasing in the range of 900 to 1800 N/s. In addition, the flexural resistance was determined according to Refs. 11, 19, using 40 × 40 × 160 mm beams that were supported on cylinders with their longitudinal axis perpendicular to these supports and leaving a 100 mm clearance to apply in the center of this, a load that increased at a speed of 50 ± 10 N/s. The test was carried out with a universal control machine, and both properties were determined at ages of 7 and 28 days.\n\n\nResults and discussion\n\nFrom the results obtained in the physical characterization of the base material, the density of the PS powder was 2084.23 (kg/m3) which is lower than that of other investigations, such as that of Ref. 20, where a PS powder with a density of 2500 (kg/m3) is used. In addition, when comparing the granulometric curves (Figure 5) of the materials used in the present study, only 24.78% of the material passed through the sieve. N°200 (0.075 mm), whereas in the research by Ref. 21, 57% of the material used passes through the No. 200 sieve, which indicates that the material used is thicker, which can be attributed to the grinding and sieving process of the material. It should be noted that the fineness of the base material affects the resistance of the analyzed geopolymer, as mentioned by Ref. 22.\n\nApplying the calculation process of number 5.4 of Ref. 15, for the determination of the modulus of fineness (MF) of the PS powder, it was determined that the modulus of fineness of the PS powder is 0.69; hence, it is considered a fine material.\n\nHowever, in the chemical characterization of the PS powder (Figure 6 and Table 6), silicon (Si) and aluminum (Al) are common denominators in the composition of the powder. PS dust from the Cotopaxi quarry is suggested by the presence of aluminosilicates, which, according to Refs. 4, 5, 20 have the potential to be pioneers in the elaboration of geopolymers.\n\nTable 6 summarizes the name of the compound, its chemical formula, and the percentage of PS powder.\n\nFrom the physical characterization of the geopolymer, density values ranging from 1645 (kg/m3) to 1726 (kg/m3) 3 were obtained (Figure 7). This material turned out to be 25% lighter than the maximum density of 2200 kg/m3 obtained by other authors as Ref. 17 of 2200 (kg/m3).\n\nThe obtained geopolymer presented an average absorption percentage of 30.79%; that is, it presented many pores, and in the presence of water, its weight increased.\n\nThe compressive strength was evaluated at 7 and 28 d in two molarities, one of 8 M and the other of 12 M, the latter being the concentration that allows reaching a compressive strength of 14.10 MPa at 10% SF replacement (see Figures 8 and 9). These results agree with the study carried out by Ref. 21, from which they concluded that the compressive strength was linked to the molar concentration and that a sodium hydroxide concentration of 12 M is the most optimal.\n\nSimilarly, when comparing the resistance of the control specimens versus those that have 10% SF replacement, the resistance increases as the percentage of SF replacement increases, with an increase of 56.31% for the concentration of 8 M and 47.59% for that of 12 M.\n\nFor resistance to flexure, the best results were obtained under the same conditions as the resistance to compression, while the maximum value obtained was 4.78 MPa. Figures 10 and 11 show that the increase in resistance between the control specimens and those with 10% SF replacement was 28.14% and 17.78% for the 8 M and 12 M molarities, respectively.\n\n\nConclusions\n\nThe PS powder used in the preparation of the geopolymer has a chemical composition that benefits its use as a precursor, because it is composed mostly of silicon and aluminum. Physically, it is a fine material with a particle size of less than 0.6 mm and a density of 2084.23 (kg/m3).\n\nIn the design of the geopolymer dosage, several factors influence the resistance, such as the ratio of sodium silicate to sodium hydroxide, water content, temperature, curing time, molarity of sodium hydroxide and alkaline solution, and binder ratio. The latter two are the most important factors to consider in terms of environmental and economic feasibility because the excessive use of the alkaline solution is counterproductive to the contribution to reducing CO2 emissions, as the production of these activators requires considerable energy consumption, which represents high production costs.\n\nThe results of resistance to compression and flexure increased up to 47% and 16% respectively, this is if the test tubes with 10% replacement of SF are compared versus the control test tubes, both with 12M molarity, in this way it is evidenced that there is a directly proportional relationship between mechanical resistance and the increase in the percentage of SF replaced.\n\nA maximum compressive strength of 14.1 MPa was reported, indicating that the geopolymer cannot be used as a structural material. However, this strength can be improved by reducing the size of the PS powder particles to a diameter of less than 0.075 mm to guarantee the dissolution and reaction of silica and aluminum, making room for polymerization of the entire material.\n\nRegarding the physical properties of the geopolymer, the density of the specimens with SF was greater than that of the control specimens because the fineness and composition of the SF fulfill the function of filling voids, thus densifying the mixture. In addition, it contributes to the formation of the polymeric gel, which is 25% lighter if the maximum density obtained is compared with that of other authors. A high percentage of absorption caused by free water stored inside the test tubes that later evaporates during oven curing has also been reported, generating a considerable number of pores that cause a decrease in resistance.",
"appendix": "Data availability\n\nThe dataset for this research has been deposited in Harvard Dataset repository and contains:\n\n- Set of analysis results for the relevant experimental processes. Available at:\n\nAndrade Valle, Alexis, 2024, “Data - Use of pumice stone and silica fume as precursor material for the design of a geopolymer”, https://doi.org/10.7910/DVN/MHO9OV, Harvard Dataverse, V2. 24\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\nUlusu H, Aruntas Y, Gencel O: Investigation on characteristics of blended cements containing pumice. Constr. Build. Mater. 2016; 118: 11–19. Publisher Full Text\n\nMallagray J, Anagnostou J, Stek M, et al.: Strengthening Sustainability in the Cement Industry. International Finance Corporation; 2020. Accessed: Apr. 15, 2024. Reference Source\n\nHardjito D, Wallah E: On the Development of Fly Ash-Based Geopolymer Concrete.\n\nOcchipinti R, et al.: Alkali activated materials using pumice from the Aeolian Islands (Sicily, Italy) and their potentiality for cultural heritage applications: Preliminary study. Constr. Build. Mater. 2020; 259: 120391–120391. Publisher Full Text\n\nHaddad RH, Lababneh ZK: Geopolymer composites using natural pozzolan and oil-shale ash base materials: A parametric study.2019. Publisher Full Text\n\nDas SK, et al.: Fresh, strength and microstructure properties of geopolymer concrete incorporating lime and silica fume as replacement of fly ash. J. Build. Eng. Nov. 2020; 32: 101780. Publisher Full Text\n\nLi OH, et al.: Evaluation of the Effect of Silica Fume on Amorphous Fly Ash Geopolymers Exposed to Elevated Temperature. Magnetochemistry. Jan. 2021; 7(1): 9. Publisher Full Text\n\nMin FS, et al.: Effect of silica fume and alumina addition on the mechanical and microstructure of fly ash geopolymer concrete. Arch. Metall. Mater. 2022; 67(1): 197–202. Publisher Full Text\n\nKockal NU, Beycan O, Gulmez N: Effect of binder type and content on physical and mechanical properties of geopolymers. Sadhana - Acad. Proc. Eng. Sci. Apr. 2018; 43(4): 1–9. Publisher Full Text\n\nPremkumar R, Hariharan P, Rajesh S: Effect of silica fume and recycled concrete aggregate on the mechanical properties of GGBS based geopolymer concrete Selection and peer-review under responsibility of the scientific committee of the Sustainable Materials and Practices for Built Environment. Effect of silica fume on the characterization of the geopolymer materials. 2022; 60: 211–215. Publisher Full Text\n\nInstituto Ecuatoriano de Normalización (INEN): NTE INEN 198: Resistencia a la flexión y compresión de morteros. Accessed: Jul. 03, 2023. Reference Source\n\nInstituto Ecuatoriano de Normalización (INEN): NTE INEN 488: Cemento Hidráulico. Determinación de la Resistencia a la Compresión de 50 mm de Arista.\n\nUNE Normalización Española: UNE-EN 1015-10:2000/A1:2007 Métodos de ensayo de los morteros. Accessed: Apr. 16, 2024. Reference Source\n\nInstituto Ecuatoriano de Normalización (INEN): NTE INEN 0856: Áridos. Determinación de la densidad, densidad relativa (gravedad específica) y absorción del árido fino.2010. Accessed: Apr. 15, 2024. Reference Source\n\nInstituto Ecuatoriano de Normalización: NTE INEN 0696: Aridos. Análisis granulométrico de agregados fino y grueso.2011.\n\nISO 9001:2015, Quality Management Systems. Accessed: Apr. 16, 2024. Reference Source\n\nOsorio B: Nuevos conglomerantes sostenibles de activación con residuos de tierra de diatomeas y cenizas de cáscara de almendra.2021. Accessed: Apr. 16, 2024. Reference Source\n\nMillán-Corrales G, Magallanes-Rivera RX, González-López JR, et al.: Synthesis of an Alternative Hydraulic Binder by Alkali Activation of a Slag from Lead and Zinc Processing. Waste Biomass Valorization. Jan. 2020; 11(1): 375–388. Publisher Full Text\n\nInstituto Ecuatoriano de Normalización: NTE INEN 2380: Cementos hidráulicos. Requisitos de desempeño para cementos hidráulicos. Accessed: Apr. 16, 2024. Reference Source\n\nMobasheri F, Shirzadi Javid AA, Mirvalad S, et al.: Durability and Mechanical Properties of Pumice-based Geopolymers: A Sustainable Material for Future. Iran. J. Sci. Technol. Trans. Civ. Eng. Feb. 2022; 46(1): 223–235. Publisher Full Text\n\nSafari Z, Kurda R, Al-Hadad B, et al.: Mechanical characteristics of pumice-based geopolymer paste. Resour. Conserv. Recycl. Nov. 2020; 162: 105055. Publisher Full Text\n\nMehta A, Siddique R: An overview of geopolymers derived from industrial by-products. Constr. Build. Mater. Nov. 2016; 127: 183–198. Publisher Full Text\n\nAndrade A, Castillo T, Paredes M, et al.: Geopolymer Designed with Pumice Stone from Ecuador. Civ. Eng. Archit. 2022; 10(5): 1864–1880. Publisher Full Text\n\nAndrade Valle A: Data - Use of pumice stone and silica fume as precursor material for the design of a geopolymer. Harvard Dataverse. 2024; V2. Publisher Full Text"
}
|
[
{
"id": "288182",
"date": "24 Jun 2024",
"name": "Abdullah Zeyad",
"expertise": [
"Reviewer Expertise Use of pumice stone in production geopolymer concrete"
],
"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\nDear authors, Please respond to the following comments. 1- The introduction requires expansion of previous relevant research. 2- List all references used in this study. 3- Provide the paper with failure models for the samples. 4- It should highlight what the research has achieved that is consistent with the purpose of the study. Thanks\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12146",
"date": "12 Aug 2024",
"name": "Andrea Zarate",
"role": "Author Response",
"response": "Dear Abdullah Zeyad Thank you for your comments, we have submitted an amended manuscript including your recommendations. 1- The introduction requires expansion of previous relevant research. Additional information has been included in the introduction. 2- List all references used in this study The reference list has been updated including the new references used. 3- Provide the paper with failure models for the samples Figure 12 and 13 have been included showing the failure models for the samples. 4- It should highlight what the research has achieved that is consistent with the purpose of the study The third conclusion highlights the importance of the use of SF in geopolymeric samples by improving the mechanical behavior. Kind Regards, The authors"
}
]
},
{
"id": "288184",
"date": "28 Jun 2024",
"name": "Dillshad K. H. Amen Bzeni",
"expertise": [
"Reviewer Expertise Concrete technology",
"special types of concrete including geopolymer concrete",
"fiber reinforced concrete"
],
"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 describes using pumice combined with silica fume as a source material to make geopolymer concrete. This research is notable because it explores alternatives to normal cement by using pumice, a naturally occurring volcanic stone present in several regions. The study attempted to improve the qualities of geopolymer material by combining silica fume and pumice in varied ratios. The paper is written in clear and accessible English, and the technique is consistent with established research methods for data collecting and presentation. The findings are reported properly. However, the text does not provide a scientific discussion or analysis of why pumice stone powder did not give adequate strength for structural concrete. Scanning Electron Microscope (SEM) investigations would have been useful for investigating the microstructure of the geopolymer material, demonstrating how silica fume increased strength, and revealing cavities and defects in the structure. The specimens' 120-hour (5-day) cure duration raises questions regarding the costs and time of geopolymer manufacture. Furthermore, the article does not identify the water-to-binder ratio, whether the water stated is part of the alkali solution or additional pure water in the mixture. The article might benefit from a more in-depth examination, including earlier data on pumice stone powder, to highlight variations in the geopolymer's characteristics compared to other research findings.\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? 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? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12147",
"date": "12 Aug 2024",
"name": "Andrea Zarate",
"role": "Author Response",
"response": "Dear Dillshad K. H. Amen Bzeni Thank you for your comments, we have submitted an amended manuscript including your recommendations. 1- The text does not provide a scientific discussion or analysis of why pumice stone powder did not give adequate strength for structural concrete. Discussion has been added to the amended manuscript, considering compressive strengths studied in other investigations. 2-Scanning Electron Microscope (SEM) investigations would have been useful for investigating the microstructure of the geopolymer material, demonstrating how silica fume increased strength, and revealing cavities and defects in the structure. Future research will include SEM of the geopolymer material as we are investigating the mechanical behavior of geopolymer using a variety of industrial residues 3-The specimens' 120-hour (5-day) cure duration raises questions regarding the costs and time of geopolymer manufacture. The research has an exploratory-correlational scope, for this reason it was not intended to find the cost-benefit through its experimental implementation in the quality control laboratory of materials, in these early stages it is only intended to meet the minimum requirements to make the applicability of the geopolymer as a binder material reliable. 4-The article does not identify the water-to-binder ratio, whether the water stated is part of the alkali solution or additional pure water in the mixture. This has been clarified in the article as the alkaline solution includes distilled water and the chemical compounds: Sodium hydroxide NaOH and Sodium silicate Na2SiO3 5-The article might benefit from a more in-depth examination, including earlier data on pumice stone powder, to highlight variations in the geopolymer's characteristics compared to other research findings. More information has been added to the amended manuscript. Kind Regards, The authors"
}
]
}
] | 1
|
https://f1000research.com/articles/13-580
|
https://f1000research.com/articles/13-917/v1
|
12 Aug 24
|
{
"type": "Research Article",
"title": "Outcomes associated with isoniazid preventive therapy for tuberculosis prevention among human immunodeficiency virus positive patients attending antiretroviral therapy clinics in Mangalore",
"authors": [
"Steffi Coelho",
"Vaishnavi Satish",
"Adail Lorainne Dsouza",
"Basavaprabhu Achappa",
"Nikhil Victor Dsouza",
"Ramesh Holla",
"Himani Kotian",
"Pavan M R",
"Steffi Coelho",
"Vaishnavi Satish",
"Adail Lorainne Dsouza",
"Basavaprabhu Achappa",
"Nikhil Victor Dsouza",
"Ramesh Holla",
"Himani Kotian"
],
"abstract": "Background The World Health Organization recommends that Isoniazid Preventive Therapy (IPT) should be administered to all People living with Human immunodeficiency virus (PLHIV) not currently suffering from tuberculosis (TB) to reduce the incidence of the same. The objectives of this study were to determine the incidence of PLHIV who contracted TB after receiving 6 months of IPT (followed up for ≥ 2 years), the incidence of PLHIV who developed tuberculosis when not on IPT, and the occurrence of adverse drug reactions due to IPT.\n\nMethods A Retrospective Cohort study was conducted in two ART centers in Mangalore, which included PLHIV who had completed 6 months of IPT from January 2017 to May 2018 and were followed up until May 2020; patients in the comparison group consisted of those attending ART centers during the same period who did not receive IPT. These data were retrieved from the case files of these patients from June to November 2020, entered into MS Excel, and analyzed using statistical package for social science (SPSS) version 25.\n\nResults The study included 1014 patients: 525 (51.8%) received IPT and 489 (48.2%) did not. Eight (1.5%) patients developed TB after IPT completion compared to 32 (6.5%) patients who developed TB from the non-IPT group. There was a 77% reduction in the incidence of developing TB in those patients who received IPT as compared to those who haven’t receive IPT (RR of 0.23, p value <0.0001). The reason for stopping IPT were due to side effects of IPT, experienced by 77 (14.6%) patients.\n\nConclusions This study indicated that the completion of IPT significantly reduced the TB burden, showing significant protection against TB for a minimum duration of 2 years. Thus, implementation of IPT should be strengthened, and strict compliance should be ensured to reduce TB infection among PLHIV.",
"keywords": [
"HIV",
"AIDS",
"TB",
"PLHIV",
"IPT",
"ART"
],
"content": "Introduction\n\nHuman immunodeficiency virus (HIV) infection is a major cause of infectious deaths worldwide. In 2017, the prevalence of HIV among adults in India was an estimated 0.22% (0.25% among males and 0.19% among females). In the same year, an estimated 69,110 people died of Acquired Immunodeficiency Syndrome (AIDS)-related causes nationally. India accounts for a high number of tuberculosis (TB) cases worldwide, with 20.2 lakh new cases annually. In addition, there is a concentrated HIV epidemic in India, focusing on a limited population due to risky behavior.1 Globally, People living with HIV (PLHIV) are 18 times more likely to contract TB infection than those without HIV (as of 2020). Moreover, TB is the leading cause of death among PLHIV worldwide, accounting for nearly 6,90,000 deaths from HIV-associated TB in 2019.2 In India, 25% of deaths among HIV patients are caused by TB.3\n\nAs part of the HIV-TB collaborative activities, the National AIDS Control Organization (NACO) and Central TB Division (CTD) jointly developed a national framework in 2008 and 2009. Interventions that decreased the morbidity and mortality due to TB in PLHIV were included, one of which is “The Three I’s. These include a) Intensified Case Finding (ICF), b) Infection Control (IC) to prevent TB in HIV care settings, and c) Isoniazid Preventive Therapy (IPT). The latter is due to the fact that Isoniazid protects against both the progression of latent TB infection (LTBI) to active disease (reactivation) as well as from reinfection when exposed to an active TB case. PLHIV who are unlikely to have active TB for a minimum of six months should be initiated on IPT as part of a comprehensive package of HIV care.3 There is substantial evidence from studies conducted all over the world to prove that the provision of IPT decreases the risk of getting infected by TB by 40% in PLHIV.4 Although the WHO has prioritized IPT recommendations for PLHIV for more than a decade, its uptake has been slow. In 2016, only approximately 42% of newly diagnosed HIV cases were initiated on IPT worldwide.5\n\nIn 2008, WHO recommended that Isoniazid Preventive therapy be administered to all PLHIV without TB disease, in localities where the prevalence of latent TB infection was more than 30%, and for all HIV patients with documented latent TB infection or those exposed to an infectious TB case, irrespective of their residence. The NACO introduced IPT as part of HIV care in 2016. It currently recommends screening all PLHIV for active TB using the WHO symptom-based screening algorithm (absence of current cough, fever > 2 weeks, night sweats, and weight loss of >3 kg within 4 weeks) and for isoniazid safety (history of chronic liver disease, seizures, use of heavy alcohol, and prior isoniazid resistance). For eligible persons, the IPT dose must be administered at 10 mg/kg/day (maximum 300 mg) for a six-month period along with pyridoxine (50 mg/day).3\n\nTuberculosis is a very common opportunistic infection among PLHIV that causes preventable acquired immune deficiency syndrome-related mortality and morbidity. In 2018, an estimated 10 million people were infected with TB worldwide, a number that has remained relatively stable in recent years. An estimate of 1.2 million deaths caused by TB among those people who were negative for HIV were reported in 2018 (a 27% reduction from 1.7 million in 2000), and an additional 2,51,000 deaths among PLHIV (a 60% reduction from 6,20,000 in 2000). India accounts for 27% of TB cases globally.6 Even PLHIV who are asymptomatic for TB need TB prophylaxis to lessen the risk of developing TB in the future, thus reducing TB/HIV death rates by approximately 40%. Approximately 49% of PLHIV and TB are unaware of their co-infection and are therefore not receiving adequate care.7\n\nDespite India having a high burden of both HIV and TB, only a few studies have been conducted to test the benefits and risks of IPT for PLHIV in Indian settings. While IPT undoubtedly reduces the incidence of TB, it is still uncertain whether there is a reduction in all-cause mortality in HIV-infected patients.8 This necessitates further studies to evaluate the outcomes associated with IPT in a programmed setting in India. The Study was conducted with the objective of determining the incidence of TB among PLHIV after receiving 6 months of IPT, who were followed up over a minimum period of 2 years. Second, to determine the burden of adverse drug reactions due to isoniazid (as documented in the case file) and the incidence of persons living with HIV who did not receive IPT and developed TB, taking into consideration that this view of the matter will help improve patient care, reduce mortality and morbidity, and take a stand against two very detrimental infectious diseases in our country.\n\n\nMethods\n\nA retrospective cohort study was conducted in two ART centers: District Wenlock Hospital, Mangalore, and Kasturba Medical College Hospital in Attavar, Mangalore. The total study population (1014 patients) included patients who were attending ART centers for the treatment of HIV who had completed 6 months of IPT from January 2017 to May 2018 and were followed up until May 2020; patients in the comparison group consisted of those attending ART centers during the same period who did not receive IPT. Data were retrieved from the case files of these patients from June to November 2020.\n\nThe study was conducted after obtaining approval from the Institutional Ethics Committee of Kasturba Medical College, Mangalore on 24th June 2020 (approval number: IECKMCMLR-06/2020/206), the Medical Superintendent of Kasturba Medical College Hospital, Attavar, and the Project Director of the Karnataka State AIDS Prevention Society, Bangalore.\n\nThe study data included details of PLHIV from the two ART centers who received IPT for six months between January 2017 and May 2018. The data collected were based on demographic details, status of HIV disease and its treatment, past history of tuberculosis and any adverse drug reactions, comorbidities, and anthropometry. The information collected included the details of any patient who developed symptoms of TB disease until June 2020. In addition, CD4 counts and other relevant laboratory investigations were recorded in the data extraction sheet. The above specifics (collected from the case files at the ART centers) were entered into MS Excel and then transferred from the data extraction sheet to a statistical package for social science (SPSS) version 25. Analysis was performed using descriptive statistics and the chi-square test, where p<0.05 is considered as statistically significant. While comparing the BMI at the time of diagnosis of HIV with the latest BMI in the IPT exposed and IPT non-exposed groups, since the data were skewed, the reported median and interquartile range were calculated and non-parametric Mann–Whitney test was performed. The relative Risk was used to compare the incidence of patients who developed TB in the IPT and non-IPT groups. To compare CD4 counts at the start of IPT with the present CD4 counts and those that did not receive IPT, the CD4 count at HIV diagnosis was compared with the present CD4 counts, and the non-parametric Wilcoxon Signed Ranks Test was performed (P <0.05, considered significant).\n\n\nResults\n\nA total of 1014 patients were included in the analysis; the study population had a male preponderance of 597 (58.9%) compared to 417 (41.1%) females. Most patients (421, 41.5%) were > 50 years of age, followed by 418 (41.2%) patients in the 40-49 years age category. A significant number of patients, 207 (20.4%), were skilled workers, and 209 (20.6%) patients were housewives. Majority of the study population resided in an urban setting, which were 550 (54.2%) patients and 464 (45.8%) patients from rural areas (Table 1).\n\nThe baseline clinical information of the patients is shown in Table 2. Most PLHIV have been on ART for 5 – 10 years, that included 531 (52.4%) patients. 377 (39.1%) patients had a CD4 count of <200 cells/mm3 at the time of HIV diagnosis. Majority of PLHIV were diagnosed at Stage I, that is, 447 (44.1%). First line ART regimen was initiated in 994 (98%) patients, whereas 20 (2%) received second line ART regimen. 838 (82.6%) patients on ART had a compliance of ≥95%, compared to 176 (17.4%) patients who were <95% compliant. 524 (51.7%) patients had no history of opportunistic infection on the other hand, 490 (48.3%) patients had an AIDS defining illness. 58 (5.7%) PLHIV were diagnosed with diabetes, and 89 (8.8%) PLHIV were diagnosed with hypertension. 643 (63.4%) PLHIV had no history of alcohol consumption, whereas 105 (10.4%) PLHIV were social drinkers. 145 (14.2%) PLHIV had a history of smoking. 573 (56.5%) patients had a viral load <1000, and in 402 patients (39.6%), the viral load target was not detected.\n\n* The variable has few missing values.\n\nThe median BMI of the patients who received IPT was 21 kg/m2 compared to the median BMI at the time of HIV diagnosis, which was 20 kg/m2. In contrast, the median BMI of patients who did not receive IPT was 22 kg/m2 compared to their median BMI at the time of HIV diagnosis, which was 20 kg/m2 (Table 3). As depicted in Figure 1, 37% of the spouses of the patients were affected by HIV.\n\nOut of 1014 patients, 525 (51.8%) patients received IPT and 489 (48.2%) did not. Among 525 PLHIV who received IPT, 8 (1.5%) patients developed TB, and among the 489 PLHIV who did not receive IPT, 32 (6.5%) patients developed TB after 2016. As per Table 4, there was a 77% reduction in the incidence of developing TB in those patients who received IPT as compared with those who haven’t received IPT (RR of 0.23, p value <0.0001). This difference was statistically significant.\n\nOf the 525 patients who received IPT, 8 developed tuberculosis after completion of the IPT course. Of the eight patients, four developed tuberculosis within 12 to 24 months after completion of the IPT course, and two patients developed tuberculosis within 12 months after completion of the IPT course (Table 5). Of the eight patients who developed tuberculosis after completion of the IPT course, two patients had a history of one episode each of pulmonary tuberculosis, one patient had pulmonary TB 6 years before commencement of IPT, and the other had a history of pulmonary TB 20 years before initiation of the IPT course. All the 8 patients had an adherence of > 80% to the IPT course.\n\nOut of 525 PLHIV who were initiated on IPT, total of 81 patients were non-adherent, out of which 4 patients finished their 6-month IPT course and had an adherence of <80%, and 77 patients discontinued their IPT course due to the side effects (Figure 2). 444 patients had an adherence to IPT treatment of more than 80%.\n\nMost patients completed the IPT course 24 to 29 months ago, which accounted for 176 patients; 150 patients completed the course 30 to 35 months back, and 122 patients completed the course ≥ 36 months back.\n\nThe median CD4 count of the 525 patients who received IPT significantly improved from 521 cells/mm3 at the initiation of IPT to 548 cells/mm3 (p <0.001) (Table 6). The median CD4 count of the 489 patients who did not receive IPT also showed a significant improvement from 276 cells/mm3 initially to 532 cells/mm3 (p <0.001). By looking into the median of the IPT Exposed patients with those that were not exposed (548 cells/mm3 and 532 cells/mm3 respectively), a minimal improvement in CD4 counts was observed in those who received IPT.\n\nThe total number of patients diagnosed with TB was 373, of which 165 developed pulmonary TB and 208 had extrapulmonary TB, of which 8 had both pulmonary and extrapulmonary TB (Figure 3).\n\nOf the 373 patients who were diagnosed with tuberculosis (irrespective of their IPT status), 348 had one episode of tuberculosis, 21 had two episodes of the disease, and four had three episodes.\n\nA significant number of patients were diagnosed at the same time with HIV and tuberculosis infection, which included 152 patients, whereas 141 patients were infected with tuberculosis after being diagnosed with HIV, and a small number (80) of patients had a history of tuberculosis at diagnosis of HIV.\n\nOf the 373 patients who were infected with tuberculosis in the past, the majority (190) had an initial CD4 count of ≥200 cells/mm3, 174 had an initial CD4 count of <200 cells/mm3, and CD4 was not documented in the remaining 9 patients (Table 7). A significant number of patients who developed tuberculosis were classified as WHO clinical HIV stages III and IV (Table 8).\n\nThis study also identified a few factors responsible for development of TB and inferred that Patients with a BMI ≥18.5 kg/m2 were 0.705 times less likely to develop tuberculosis (OR= 0.705; 95% CI: 0.539-0.923). The PLHIV at WHO clinical stages III and IV had 17.287 times higher risk of acquiring TB than those who were at WHO clinical stages I and II (OR = 17.287; 95% CI: 12.534-23.844). Patients who had a baseline CD4 count of ≥ 200 cells/mm3 were 0.525 times less likely to develop TB than those with a CD4 count < 200 cells/mm3 (OR = 0.525; 95% CI: 0.402-0.686).\n\n\nDiscussion\n\nIn our study, A total of 1014 patients were included in the analysis, the study had a male predominance of 597 (58.9%) compared to 417 (41.1%) females. Out of 1014 PLHIV, 421 (41.5%) patients were above 50 years of age, 418 (41.2%) were in the age group 40–49 years, 115 (11.3%) were within 30–39 years, and 60 (5.9%) were below 30 years of age. Majority of the study population resided in an urban setting, which were 550 (54.2%) patients, compared to 464 (45.8%) patients from a rural area.\n\nIn this study, 525 (51.8%) PLHIV were subjected to IPT, 444 (84.5% of the 525 PLHIV) of the patients who received IPT had an adherence of more than 80% to IPT compared to 81 (15.42%) patients who were non-adherent, out of which 4 (0.76%) patients finished their 6-month IPT course and had an adherence of <80%, and 77 (14.6%) patients discontinued their IPT course. The four patients who completed IPT course and had an adherence to IPT less than 80% were all males, between the age group 40 and 50 years, three out of the four patients had a history of either smoking, alcohol, or tobacco consumption.\n\nThe reasons for stopping IPT were mostly medical reasons, including fatigue, which was detected in 28 patients, followed by gastritis in 16 patients, giddiness in 12 patients, peripheral neuropathy in 12 patients, myalgia in 3 patients, 2 had skin rashes, 1 patient each had other symptoms, including jaundice, vomiting, psychosis, or gynecomastia. Our study considered 80% as a cut off for good adherence, as recommended by WHO, the data for adherence to IPT were collected by going through the monthly documented data in the patients’ ART cards.\n\nAdherence to a regimen plays a major role in its effectiveness. Infection with both TB and HIV causes compliance problems because of the high pill burden and adverse effects. In Addis Ababa, a cross-sectional study was conducted to explore the compliance of PLHIV to IPT. The adherence to IPT was found to be 89.5%. Patients who were on ART were more adherent than those who were on pre-ART. Patients who were counselled about IPT by their healthcare workers were more adherent than those who were uninformed about the reason for taking IPT. They concluded that adherence to IPT was high, suggesting that counselling should be strengthened for patients in the first two months of therapy.9\n\nA Study conducted in Tanzania by Munseri, P.J.; Talbot, E.A. et al. to examine factors related to IPT completion among PLHIV in Tanzania, inferred that out of 565 subjects who were initiated on IPT, 87% among them completed the course and 13% did not. Non- compliance was physician-initiated in 33% of the patients, due to active TB or side effects, patient-initiated in 58%, as they were lost to follow-up or due to self-cessation, and 8% were due to patient demise (unrelated to IPT). After questioning patients, it was inferred that those who completed the course did so due to TB fear (44%), understood the importance of IPT (32%), and were counselled (22%). While those patients who did not complete the course were discouraged by stigma (58%), side effects (14%), and commute (1%), their study concluded that PLHIV who were counselled, had regular follow ups monthly and those who were provided with reimbursement for travel had high IPT completion rates with fewer adverse effects.10\n\nIn our Study, 525 patients received IPT, out of which 8 (1.5%) patients developed tuberculosis after completion of the IPT course as per the data that was retrieved from the case cards for over a minimum period of 2 years post IPT as compared to the other prospective pilot study.11 Of the eight patients, four developed tuberculosis within 12 to 24 months after completion of the IPT course, two patients developed tuberculosis within 12 months after IPT completion, one patient contracted tuberculosis within 25 to 36 months from IPT completion, and one patient developed tuberculosis infection 36 months after IPT completion.\n\nOf the eight patients who developed tuberculosis after completion of the IPT course, two patients had a history of one episode each of pulmonary tuberculosis previously and were treated for the same, one patient had pulmonary TB 6 years before commencement of IPT, and the other had a history of pulmonary TB 20 years before initiation of the IPT course; these patients could have developed isoniazid drug resistance that led to failure of IPT. All the 8 patients had an adherence of > 80% to the IPT course, 2 patients from the 8 patients, had an adherence of 85% and one patient had adherence of less than 95%, which could be the reason for failure of IPT; the remaining 5 patients had a CD4 count <500 cells/mm3 when IPT was initiated and a further decline in their CD4 count to <300 cells/mm3 was observed in the year 2020; the mean CD4 count of the 8 patients at the time of receiving IPT was 485.13 ± 194.161 and the mean CD4 count in the year 2020 reduced to 320.13 ± 182.060;, therefore a low CD4 count could be the reason for tuberculosis infection in these patients. Of 489 patients who were not initiated on IPT, 32 (6.5%) patients developed TB after 2016, of which 6 patients had a prior infection of TB before 2017. There was a 77% reduction in the TB incidence among those patients who received IPT as compared with those who did not receive IPT. (RR of 0.23, p value <0.0001)\n\nA multicenter, prospective pilot study was conducted in seven ART centers in urban and semi-urban Indian cities. Monthly counselling and symptom review were conducted during the IPT course and for 6 months after completion of IPT. Their study reported that the TB incidence rate during 6 months after IPT completion was 0.64/100 p-y (95% CI 0.04-1.12) as compared to 2.42/100 p-y (95% CI 1.90-3.10) during the pre- IPT period. The IPT side effects were less than 5%, of which vomiting and skin rash were the most common.11\n\nIn the Thibela TB study, they concluded that TB disease among PLHIV who had a prior exposure to IPT had typical outcomes of their treatment similar to their setting and a similar prevalence of isoniazid resistance to background, and that concerns of drug resistance should not prevent the implementation of IPT.12\n\nIn a Study conducted in Chennai to assess the efficacy of IPT in decreasing the incidence of TB in a cohort of PLHIV between 2012 and 2015 in four states of India, data were collected from nine ART centers. After counselling, eligible PLHIV commenced the IPT course for a duration of 6 months. This study concluded that IPT was effective in reducing incidence of TB in India by almost 50% under programmed conditions and setting the stage to enable and strengthen the IPT services along with ART, which will have a beneficial effect in lowering the TB burden among PLHIV.3\n\nAnother Study conducted in Western Ethiopia inferred that the incidence rate of TB in the IPT group was 1.98 per 100 p-y and in the non-IPT group was 4.52 per 100 years. This study identified various predictors of TB. Compared to patients who were at WHO clinical stage I or II, PLHIV at stage III or IV had 3.22 times greater risk of acquiring TB. They also reported that patients with a baseline CD4 count <200 cells/μL were 15 times more likely to develop TB than those with a CD4 count > 500 cells/μL. Their study reported that patients with BMI <18.5 kg/m2 had a 1.85 greater chance of getting infected with TB than those with BMI > 18.5 kg/m2.13\n\nIn our study, binary logistic regression was performed to compare the risk factors for TB infection with respect to baseline CD4 count, BMI value, and WHO clinical staging. 373 (36.7%) PLHIV had a past infection of TB, irrespective of their IPT status, of which 259 (43.3%) were male and 114 (27.3%) were female. 165 (44.2%) patients had pulmonary tuberculosis, compared to 208 (55.7%) patients who had extra- pulmonary tuberculosis, among which abdominal TB (2.8%) was most common, followed by TB meningitis (2.2%). Our study identified several risk factors for tuberculosis among PLHIV enrolled on ART irrespective of their IPT status, out of the 373 PLHIV who were diagnosed with tuberculosis, 174 (46.6%) patients had a CD4 count of less than 200 cells/mm3. Patients who had a baseline CD4 count of more than or equal to 200 cells/mm3 were 0.525 times less likely to develop TB than those patients whose baseline CD4 count were less than 200 cells/mm3 (OR = 0.525; 95% CI: 0.402, 0.686). Patients who had a BMI of more than 18.5 kg/m2 were 0.705 times less likely to develop tuberculosis when compared to the underweight patients (OR= 0.705; 95% CI: 0.539, 0.923). A significant number of patients who developed tuberculosis were classified as WHO clinical HIV Stage III (152 patients) and Stage IV (145 patients). The PLHIV at WHO clinical stages III and IV had 17.287 times the risk of acquiring TB than those who were at WHO clinical stages I and II (OR = 17.287; 95% CI: 12.534, 23.844).\n\nThe authors have not preregistered the research at any independent registry.\n\n\n\n1. A large number of patients with varied demographics were included in this study.\n\n2. Both the ART centers in Mangalore were covered in the study.\n\n\n\n1. The retrospective nature of the cohort study included certain problems, such as data inconsistency and incompleteness, where certain data in a few patients, their initial CD4 counts, and the initial ART regimen were not documented due to transfers between ART centers. Data were limited to the information entered into the ART Cards.\n\n\nConclusion\n\nA Good adherence to IPT above 80% was observed in our study in 84.5% of the 525 PLHIV who were started on IPT. The proportion of PLHIV who contracted TB after six months of IPT was 1.5% of patients. The proportion of PLHIV who did not receive IPT and developed TB was 6.5% of patients. There was a 77% reduction in the incidence of TB in those patients who received IPT as compared with those who haven’t received IPT (RR of 0.23, p value <0.0001).\n\nThe failure of IPT could be attributed to an adherence of < 95% and a CD4 count of less than 500 cells/mm3 during IPT initiation. Further research is required to explore IPT resistance. The reasons for stopping IPT were mostly due to medical reasons that were the side effects of IPT, which were experienced by 14.6% of patients who were on IPT. The most common side effect is fatigue, followed by gastritis.\n\nThis study concluded that good adherence to IPT and completion of the IPT course significantly reduced the TB burden.\n\n\nEthics and consent\n\nThe study was conducted after obtaining approval from the Institutional Ethics Committee of Kasturba Medical College, Mangalore on 24th June 2020 (approval number: IECKMCMLR-06/2020/206), the Medical Superintendent of Kasturba Medical College Hospital, Attavar, and the Project Director of the Karnataka State AIDS Prevention Society, Bangalore.\n\nConsent was waived off by the ethical approval committee. We obtained permission from the Medical Superintendent of Kasturba Medical College Hospital, Attavar, and the Project Director of Karnataka State AIDS Prevention Society, Bangalore, before commencement of the study. All the information collected from the patients’ case files was coded to maintain confidentiality.\n\n\nAuthor contributions\n\nSteffi Coelho: Data curation, investigation, methodology, project administration, writing-original draft preparation, writing-review and editing and visualization.\n\nVaishnavi Satish: Investigation, writing-review and editing, methodology and visualization.\n\nAdail Lorainne Dsouza: Investigation, writing-review and editing, methodology and visualization.\n\nBasavaprabhu Achappa: Conceptualization, methodology, supervision, validation, project administration.\n\nNikhil Victor Dsouza: Conceptualization, methodology, supervision.\n\nRamesh Holla: Formal analysis, methodology, software.\n\nHimani Kotian: Formal analysis, methodology, software.\n\nPavan M R: Supervision, validation.",
"appendix": "Data availability\n\nIndicators and Variables\n\nFigshare: IPT excel.xlsx (demographic and medical information of patients), https://doi.org/10.6084/m9.figshare.24543280.v1. 14\n\nThe dataset generated from patients’ clinical records is available under the terms of CC-BY 4.0 Creative Commons Attribution Only license.\n\n\nAcknowledgments\n\nWe are extremely grateful and thank all the healthcare workers in the HIV care services in the two ART centers – District Wenlock Hospital, Mangalore and Kasturba Medical College Hospital in Attavar, Mangalore. We also want to express our appreciation to the Karnataka State AIDS Prevention Society for granting us permission to conduct the study at the ART center in the Government Wenlock Hospital, Mangalore.\n\n\nReferences\n\nNational AIDS Control: (accessed on 20th March 2020). Reference Source\n\nWHO Factsheet on HIV-associated TB: (accessed on 20th March 2020). Reference Source\n\nOperational manual of Isoniazid preventive therapy, June 2016. P6, 8, 9, 15-18. (accessed on 20th March 2020). Reference Source\n\nGodfrey-Faussett P: Policy statement on preventive therapy against tuberculosis in people living with HIV. Geneva: World Health Organization; 1998 Feb.\n\nWorld Health Organization: Global tuberculosis report 2018. World health organization; 2018.\n\nWorld Health Organization: World Health Organization Global Tuberculosis Report 2019. Geneva, Switzerland: World Health Organization; 2019. (accessed on 20th March 2020). Reference Source\n\nGlobal HIV AIDS statistics—2018 fact sheet. Geneva: UNAIDS; 2019 May. (accessed on 22nd March 2020). Reference Source\n\nBriggs MA, Emerson C, Modi S, et al.: Use of isoniazid preventive therapy for tuberculosis prophylaxis among people living with HIV/AIDS: a review of the literature. J. Acquir. Immune. Defic. Syndr. 2015 Apr 15; 68: S297–S305. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBerhe M, Demissie M, Tesfaye G: Isoniazid preventive Therapy Adherence and associated Factors among HIV Positive patients in Addis Ababa, Ethiopia. Adv. Epidemiol. 2014 Jul 22; 2014: 1–6. Publisher Full Text\n\nMunseri PJ, Talbot EA, Mtei L, et al.: Completion of isoniazid preventive therapy among HIV-infected patients in Tanzania. Int. J. Tuberc. Lung Dis. 2008 Sep 1; 12(9): 1037–1041. PubMed Abstract\n\nPadmapriyadarsini C, Sekar L, Reddy D, et al.: Effectiveness of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected adults in programme setting. Indian J. Med. Res. 2020 Dec 1; 152(6): 648–655. PubMed Abstract | Publisher Full Text\n\nVan Halsema CL, Fielding KL, Chihota VN, et al.: Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in a high HIV prevalence setting. AIDS. 2010 Apr 24; 24(7): 1051–1055. PubMed Abstract | Publisher Full Text\n\nTiruneh G, Getahun A, Adeba E: Assessing the impact of isoniazid preventive therapy (IPT) on tuberculosis incidence and predictors of tuberculosis among adult patients enrolled on ART in Nekemte Town, Western Ethiopia: a retrospective cohort study. Interdiscip. Perspect. Infect. Dis. 2019 May 2; 2019(1): 1–8. Publisher Full Text\n\nFigshare: IPT excel.xlsx (demographic and medical information of patients). [Data set]. Publisher Full Text"
}
|
[
{
"id": "334463",
"date": "04 Nov 2024",
"name": "Lucy Chimoyi",
"expertise": [
"Reviewer Expertise Infectious disease epidemiology",
"TB and HIV 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\nThe authors have submitted an article of great interest. TPT delivery outcomes in routine settings are rarely reported on but are important in assessing the success of TPT programmes among PLHIV. The article is therefore very important in this field.\nI have provided my review comments after thoroughly reading this article\nIntroduction\n2nd paragraph: what are some of the reasons for a slow IPT uptake? 3rd Paragraph: Can the authors clarify whether WHO recommended IPT for PLHIVs without TB disease in 2008 or 2011? Provide a citation for the statement. What is the situation regarding TPT in PLHIVs in India? That is largely missing from the introduction.\n\nMethods\nA brief description of the two ART centres is important. What is the headcount? How many ART patients? What are the different regimens (1st and 2nd line treatments)? How many TB diagnosis reported? Why were the two health facilities selected? In the methods, it is worthwhile to explain the TPT programme.\nAre PLHIV prescribed the IPT monthly for the entire six months period? or is a multi-month dispensing approach followed? If yes, how many months would one be prescribed IPT? How are AEs documented? How is TB diagnosed (probable or definite)? How was IPT completion/adherence documented and assessed? Is counselling offered before IPT start, during IPT uptake?\n\nHow was the sample size of 1014 calculated? Did the patients give permission for researchers to access their files? Mention that a regression analysis was conducted to assess factors associated with incident TB. This is missing from the methods section but the authors have reported findings from this type of analysis. Include the citation for SPSS program\n\nResults\nTable 2: Include footnotes to explain terms that may not be obvious to readers not familiar with your setting. For instance,\nwhat does ART compliance threshold of 95 mean? What is H/o? What is TND?\n\nIt is not very clear why Figure one is relevant. There is no mention of this in the Introduction or methods. Are the authors trying to bring in an element of potential household contacts? I would leave this figure out. This statement is confusing” “Of the 373 patients who were diagnosed with tuberculosis (irrespective of their IPT status), 348 had one episode of tuberculosis, 21 had two episodes of the disease, and four had three episodes.” Earlier on, when reporting the RR, the authors reported that 40 TB diagnosis were made. The former statement reports more than 40 cases. Can the authors clarify which is which. Were these 373 PLHIVs latently infected?\n\nDiscussion\nThe authors should summarize their main findings and not repeat what has been written in the results section. What was the aim of the study or objective? Therefore, the authors should mention this in the first paragraph of the discussion. 4th paragraph: Authors assert that patients who were on ART were more adherent than those who were on pre-ART. However, there are no results presented to support this finding. Can the authors include these in Table 2?\n\nConclusions\nThe main reason for stopping IPT were medical, but the authors have not provided the results to support this. Did the patients stop completely or interrupted briefly and the continued? To make this assertion, it is important to comprehensively explain this in the methods section. What is the WHO definition for treatment completion?\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?\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": []
}
] | 1
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https://f1000research.com/articles/13-917
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https://f1000research.com/articles/13-677/v1
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24 Jun 24
|
{
"type": "Review",
"title": "Tourette syndrome research highlights from 2023",
"authors": [
"Andreas Hartmann",
"Per Andrén",
"Cyril Atkinson-Clement",
"Virginie Czernecki",
"Cécile Delorme",
"Nanette Mol Debes",
"Simon Morand-Beaulieu",
"Kirsten Müller-Vahl",
"Peristera Paschou",
"Natalia Szejko",
"Apostolia Topaloudi",
"Kevin J. Black",
"Per Andrén",
"Cyril Atkinson-Clement",
"Virginie Czernecki",
"Cécile Delorme",
"Nanette Mol Debes",
"Simon Morand-Beaulieu",
"Kirsten Müller-Vahl",
"Peristera Paschou",
"Natalia Szejko",
"Apostolia Topaloudi",
"Kevin J. Black"
],
"abstract": "In this, the tenth annual update for the F1000Research Tics collection, we summarize research reports from 2023 on Gilles de la Tourette syndrome and other tic disorders. The authors welcome article suggestions and thoughtful feedback from readers.",
"keywords": [
"Tics",
"Tourette",
"annual review"
],
"content": "Introduction\n\nThis article is the tenth annual update for the F1000Research Tics collection, and is meant to disseminate scientific progress on Tourette Syndrome (TS) that appeared in the year 2023. We searched PubMed using the search strategy (“Tic Disorders”[MeSH] OR Tourette) NOT ((Tourette[AU] OR Tourette[COIS]) NOT (“Tic Disorders”[MeSH] OR Tourette [tiab])) AND 2023[PDAT] NOT 1800:2022[PDAT]. On 16 Jan 2024 this search returned 278 citations. A search of PubMed Central for “tic disorders”[mesh] OR tourette*[ti] OR tourette*[ab] OR Tourette*[kwd] OR tourettism[tw] AND 2023[dp] NOT 1800:2022[dp] on the same date returned 218 citations, many overlapping. All these citations are available at this link. Colleagues also recommended articles, and we attended selected medical conferences. We selected material for this review subjectively, guided by our judgment of possible future impact on the field. The authors eagerly invite article suggestions for next year’s highlights article at https://www.authorea.com/697735/.\n\n\nMain body\n\nDefinition and phenomenology\n\nBaizabal-Carvallo and colleagues examined 156 patients with TS and 38 patients with secondary tic disorders (of whom some had functional tics) by evaluation of video-recordings and assessment of the clinical history (Baizabal-Carvallo et al. 2023). Compared to patients with secondary tic disorders, patients with TS were more likely to have earlier onset of tics, greater complexity and severity of tics, and tics affecting primarily the head and neck area. Furthermore, patients with TS were more likely to be male. They suggest considering another tic disorder than TS if these characteristics are absent. The same group examined differences between oromandibular tics and tardive dyskinesia. Forty-one patients were identified with oromandibular tics and these were compared with 35 patients with classic tardive dyskinesia. The latter group of patients was found to have more frequent continuous tongue, oromandibular and masticatory movements (Baizabal-Carvallo et al. 2023). According to another study by Baizabal-Carvallo and colleagues, blocking tics occur in 6% of patients (12/201). The most common type of blocking phenomenon was arrest in speech, followed by motor blocking phenomena. There was a correlation between blocking tics and the presence of dystonic tics and the number of phonic tics (Baizabal-Carvallo and Jankovic 2023).\n\nSeveral studies have examined gender differences in children and adolescents with tics (Larsh et al. 2023a, 2024; Nilles et al. 2023a). Gender differences in tic- and non-tic-related impairment were examined in 132 adolescents aged 13-17 years (Larsh et al. 2023a). Tic- and non-tic-related impairment were higher in adolescent girls then in boys, and in girls parent-reported non-tic-related impairment was correlated with symptoms of OCD. In a second study, sex differences in tic severity by retrospectively reviewing Yale Global Tic Severity Scale (YGTSS) measures in 373 adolescents (13-17 years) before coronavirus disease 2019 (COVID-19) pandemic and during the pandemic (Larsh et al. 2024). There was no difference in tic severity between the sexes before the pandemic, but during the pandemic where girls had more severe tics than boys. Nilles and colleagues assessed the influence of sex and age on the phenomenology of tics by examining 203 children and adolescents using the YGTSS (Nilles et al. 2023a). Both were found to affect tics; females had higher frequency and intensity of motor tics than males and this was associated with a greater impairment. Age was positively correlated with total tic severity score.\n\nAssessment and quantification of tics\n\nThe Motor Tic, Obsession and Compulsion and Vocal Tic Evaluation Survey (MOVES) is an established assessment for tics. Lewin and colleagues evaluated whether only subset of questions can be used as a short screening tool. Both version of the scale demonstrated good sensitivity and specificity was acceptable in comparison to expert assessment (Lewin et al. 2023).\n\nTwo machine learning algorithms for automatic tic detection were evaluated in 64 videos on 35 patients with TS (Brügge et al. 2023). Tic detection F1 scores (79.5-82.0%) showed that the algorithms are feasible and reliable and might become useful in the assessment and differential diagnosis of tics.\n\nRiechmann and colleagues revised the Rush Video-Based Tic Rating Scale in order to improve the use in research settings (Riechmann et al. 2023). In total, 102 videos of patients with TS or persistent motor tic disorder were included. Reducing the video time from 10 minutes to 5 minutes did not lead to significant changes in the assessment of tic frequencies. Furthermore, proposed adaptions in anchor values for tic frequency improved correlation with the YGTSS Score, and psychometric properties were acceptable.\n\nPrognosis and natural history\n\nIn a nationwide cohort study in Sweden, 3761 individuals with tic disorders in childhood were included in order to examine the prevalence and risk factors for the persistence of tic disorders into adult life (Mataix-Cols et al. 2023). In total, 20% of children with tic disorder received a chronic tic disorder diagnosis in childhood. The strongest risk factors for tic persistence were psychiatric comorbidity in childhood and family history of psychiatric disorders.\n\nSensory phenomena and premonitory urge\n\nIn this online study, the authors investigated the nature of non-just-right experiences (NJRE) that have been previously linked to premonitory urges (PU) as well as to obsessive-compulsive disorders (OCD) (Brandt et al. 2023a). One hundred eleven patients with TS completed different self-assessments for tics, PU and comorbid OCD/obsessive compulsive behaviors (OCB). NJRE were more related to the OCD spectrum than to PU or tics. The same group (Brandt et al. 2023b) examined clinical characteristics of PU in a large cohort of patients with chronic tic disorders (n=291). PU varied with tic severity. In the vast majority of patients, tics were followed by relief of the urge. ADHD, depression, female gender, and older age were identified as factors associated with the presence of PU. By contrast, OCD and younger age were associated with higher urge intensity.\n\nLarsh and colleagues used a combined approach to determine whether cortical properties such as excitability (CE) as well as cortical inhibition (LICI) correlate with PU and tics. In line with previous studies, PU intensity correlated with tic severity, and higher urge severity correlated with lower CE and LICI (Larsh et al. 2023b).\n\nLi and colleagues published results of a systematic review and meta-analysis investigating relationship between urge severity and neuronal correlates (Li et al. 2023). Altogether, 22 studies were identified with a total of 1236 patients. A meta-regression demonstrated that age and tic severity were related to PU severity. From a neuroanatomical perspective, PU was related to the following regions of the brain: insula, prefrontal cortex, anterior cingulate cortex, and supplementary motor area.\n\nA study from Japan explored pre-movement gating (attenuation) using somatosensory evoked potentials (SEPs) (Kimura et al. 2023). The authors found that sensorimotor processing was preserved for simple tics but impaired for complex tics in a group of individuals after middle adolescence.\n\nTransient effects of environment on tic severity\n\nA fascinating study from Israel examined the timing of tics moment to moment while children with tic disorders watched a movie and played a video game (Raz et al. 2024). Tics did not occur randomly over time but rather were more or less common across participants during specific moments of the movie clip and when reward was expected in the video game. One interesting hypothesis presented for future study was that “the portrayal of motor actions in movies elicits” an urge to tic. Similarly, one would be very interested in whether movie or game conditions eliciting higher tic rates correspond to greater release of striatal dopamine in people with and without tics (Koepp et al. 1998).\n\nA group from Italy explored the impact of SARS-COV-2 infection in children and adolescents with TS (Prato et al. 2023). Participants who had COVID-19 infection experienced both short-lasting as well as long-lasting symptoms (“long COVID”). Of note, 35% of patients experienced worsening of tics and/or of psychiatric comorbidities. The impact of the COVID-19 pandemic on tics was also investigated by Hall and colleagues (Hall et al. 2023). The authors compared YGTSS scores before and during the pandemic in children and young people (N = 112). No significant differences were found between the two assessments.\n\nIn a population-based study, Jack and colleagues reported that the incidence of tics in children and young people increased across all age and sex groups during the COVID-19 pandemic, especially in teenage girls (Jack et al. 2023). However, it is plausible to speculate that many of the patients diagnosed with tics in fact had FTLB, since it is well known that the incidence of FTLB dramatically increased during the pandemic and many of these patients were misdiagnosed with TS.\n\nFunctional tic-like behaviors\n\nVarious authors have identified differences in the frequency or character of premonitory phenomena (PU) as a potential feature that can discriminate functional tic-like behaviors (FTLB) from primary tic disorders (Malaty et al. 2022; Martino et al. 2023). The frequency of PU in those prior reports differed to a clinically important degree from the frequency in typical tic patients at a similar disease duration (Arbuckle et al. 2022). However, prospectively comparing 83 patients with typical tics and 40 with FTLB from the Calgary tic registry, Szejko and colleagues found no significant differences in premonitory urge severity (PUTS scale total score) nor in any of the individual PUTS items (Szejko et al. 2023). The authors noted that their results are supported by other reasonably large case series (Fremer et al. 2022; Buts et al. 2022), and provide a brief but compelling discussion of potential implications.\n\nClinical differences between functional tics and neurodevelopmental tics were confirmed in a study by Cavanna and colleagues (Cavanna et al. 2023a). In this study, 105 consecutive patients who had developed functional tics in the period from April 2020 to March 2023 were examined using a neuropsychiatric assessment. Besides the (sub-) acute onset and high frequency of complex movements and vocalizations, it was shown that 23% of patients had a pre-existing tic disorder, 70% had comorbid anxiety, 40% had a comorbid affective disorder, and 41% had at least one other functional neurological disorder. The same group directly compared the clinical features of patients who developed functional tics during the COVID-19 pandemic (N = 83) to patients with TS matched for age and gender (N = 83) (Cavanna et al. 2023b). This comparison identified many variables previously reported to differ between the two groups, but the statistically strongest indicators were “tic-related obsessive-compulsive behaviors” and a family history of tics, both of which were much more common in typical TS. Another interesting study on this topic by the same group (Cavanna et al. 2023c) compared 66 patients with FTLB with 44 patients with other functional movement disorders (FMD), namely functional symptoms suggesting dystonia, tremor, gait disorder, and myoclonus. While both groups shared some characteristics such as female preponderance, comorbid anxiety, depression, other functional neurological symptoms, and subacute onset of symptoms, patients with FTLB had an earlier age of symptom onset and were more frequently exposed to social media than those with other forms of FMD.\n\nFremer and colleagues (Fremer et al. 2024) compared a group of patients with FTLB (n=32) with a very large sample of patients with tics (n=1032). A number of previously reported characteristics of FTLB could be replicated: older age of onset, higher proportion of females, and higher rate of obscene and socially inappropriate behaviors. Interestingly, patients with FTLB had significantly lower rates of psychiatric comorbidities typically seen in TS such as ADHD and OCD. Phenotypic differences between patients with FTLB (n=53) and tics (n=200) were also analyzed by a group of researchers from Denmark (Andersen et al. 2023a). Patients with FTLB were found to have more complex symptoms, were older at symptom onset, were more frequently females, and had less frequently a positive family history for tics. As a new finding, they reported that patients with FTLB had more family members with psychiatric disorders and more often had a history of trauma preceding the onset. In another Danish study, Okkels and colleagues described a cohort of patients with FTLB (Okkels et al. 2023). Again, most were females, and had mainly complex movements with no rostrocaudal progression. Almost 70% reported harmful behaviors, and 96% had exposure to relevant social media.\n\nAs noted above, patients with TS are not immune from developing FTLB in addition to pre-existing developmental tics. This association is not surprising, as for example pseudoseizures are more common in people with epilepsy. Müller-Vahl et al. (2024) presented data on 71 TS patients whom they also diagnosed with FTLB. A majority (56%-79%) had psychological features common in people with other functional symptoms, and about a third of them had a history of other medically unexplained symptoms; these findings suggest that the cause of FTLBs is likely similar to that of other functional neurological symptoms. The authors comment that their ability to identify a fairly large sample of TS+FTLB suggests that clinicians faced with treatment-resistant symptoms in TS should consider whether the symptoms are FTLB rather than tics.\n\nFinally, an international group of experts published results of the so far largest group of patients with FTLB seen in multiple centers across the globe (Martino et al. 2023). Altogether, 294 patients with FTLB were included. The vast majority were adolescents and young adults (97%), 87% were females, 70% presented with rapid symptom progression, and spontaneous remission was noted in 20% of cases. From the phenomenological perspective, 85% demonstrated complex movements and 81% complex vocalizations. One fifth had a preexisting tic disorder, 66% had anxiety, around 30% depression, 24% autism, and 23% ADHD. Again, a high number (60%) reported exposure to social media.\n\nDiagnostic agreement in assessing FTLB was examined by asking eight experts in diagnosing and treating patients with tics to evaluate videos from 24 adults and diagnose them with either functional tics, primary tics or both (Rigas et al. 2023). The diagnostic agreement was based on phenomenology alone, and increased to moderate when additional clinical information was provided. However, the diagnostic distinction between primary and functional tics was shown to be difficult in the absence of clinical information.\n\nRegarding long-term prognosis in 83 youth 83 youth with FTLB, Nilles and colleagues observed a meaningful improvement of FTLB over a period of 12 months suggesting an overall good prognosis (Nilles et al. 2024).\n\nComorbidities\n\nSadeh and colleagues examined the presence of depressive symptoms in a cohort of 85 children and adolescents with chronic tic disorders (CTD), aged 6-18 years, using the Child Depression Inventory (Sadeh et al. 2023). In total, 21% had depressive symptoms and the presence of depressive symptoms was correlated with the presence of comorbid OCD and/or ADHD. Furthermore, symptoms of depression moderated the correlation between tic-related impairment and tic severity. Therefore, the authors suggest that it is important to screen and treat depression in children with CTD.\n\nThe presence of depression and anxiety were assessed in several other studies. Isaacs and colleagues examined a population of 120 adult patients with CTD with several scales as part of routine care (Isaacs et al. 2023). Symptoms of anxiety were more common than depressive symptoms. Anxiety, depressive and OCD symptom severity were significantly associated to each other, but not to tic severity. In a systematic review and meta-analysis including twelve studies from 1997-2022, the prevalence of anxiety and depression in TS was estimated at 36.4% and 53.5% respectively (Abbasi et al. 2023).\n\nKoenn and colleagues examined impulsivity in its multidimensional aspects. They compared 16 patients with OCD, 14 patients with TS and 28 healthy subjects using the self-rated Barratt Impulsiveness Scale BIS-11 (attentional, motor, non-planning) and a continuous performance test assessing sustained attention, working memory, and cognitive impulsivity. Both patients with OCD and patients with TS showed significant deficits in attention via self-assessment, but no difference was observed in the behavioral test. Tic severity was strongly correlated with attentional impulsivity. The authors concluded that a detailed interpretation of the various tools for measuring impulsive behavior is necessary.\n\nLiu and colleagues surveyed behavioral problems in children with tic disorders in order to develop a model for predicting behavioral problems based on sociodemographic and clinical characteristics (Liu et al. 2023). They used the Achenbach Child Behavior Checklist (CBCL) in a total of 343 children and showed that 30.3% had behavioral problems. The best predictors were age 12 to 16 years, abnormal birth history, an indulgent parenting pattern, parents or close relatives with tics or other psychiatric disorders, and tic severity.\n\nRizzo and colleagues carried out a systematic review of social cognition studies in several hyperkinetic movements disorders (Huntington’s disease, dystonia, essential tremor and TS) in accordance with PRISMA guidelines (Rizzo et al. 2023). This meta-analysis of 50 studies revealed impairments in Theory of Mind and social perception in all hyperkinetic movement disorders, as well as impairments in empathy in HD and TS patients. These findings suggest that individuals with TS may exhibit hypersensitivity toward interoceptive experiences associated with social stimuli due to the altered connectivity with striatal-corticothalamic circuits involved in symptom generation.\n\nColautti and colleagues studied the creative skills of TS patients in order to know if they could help them better manage their symptoms in their daily lives (Colautti et al. 2023). Creative thinking is generally defined as the ability to generate an idea that is both innovative (or original) and useful (or appropriate). It distinguishes between divergent thinking, which refers to the ability to produce multiple different solutions to open questions, and convergent thinking which involves the search for a single solution to a well-defined problem by appealing to persistence and focus. The study compared a group of 25 patients with TS and 25 healthy matched controls on different experimental creative thinking tasks and questionnaires. The results showed that TS patients outperformed healthy controls in convergent thinking, and that good divergent thinking could enable better coping with tics in everyday life. The authors concluded that creative thinking can serve as a cognitive resource for non-pharmacological interventions.\n\nSleep problems were explored in two studies. Colreavy and colleagues found that sleep patterns was more impacted by the pandemic in children with TS than in typically developing children (Colreavy et al. 2023). Using a naturalistic, longitudinal approach, Keenan and colleagues found that children with TS spend significantly more time in bed, have increased sleep onset latency, reduced sleep efficiency, and lower subjective sleep quality compared to healthy controls, whereas sleep time is comparable (Keenan et al. 2024). In contrast to clinical observations, self-reported tic severity was not related to increased sleep onset latency. More than 80% of children with TS fulfilled diagnostic criteria for a sleep disorder, highlighting the importance for screening for sleep difficulties in clinical routine.\n\nKurvits and colleagues investigated the prevalence of compulsive sexual behaviors and paraphilic interests in adults with chronic tic disorders (Kurvits et al. 2023). In contrast to previous reports, these symptoms were found at the same rate as in the general population. There was also no association with the use of antipsychotics, though in other populations case reports have linked partial dopamine agonists to disinhibited behavior. ADHD was a risk factor for paraphilic interests and compulsive sexual behaviors.\n\nThe Danish TS Study Group published the results of a longitudinal study investigating substance use in pediatric patients with TS (Andersen et al. 2023b). Comorbid ADHD and lower socioeconomic status of the guardian predicted higher risk for tobacco smoking, while coexisting OCD was a protective factor.\n\nTygesen and colleagues compared fine motor skills in children with TS with their healthy siblings and matched healthy controls, but failed to demonstrate any differences between these three groups (Tygesen et al. 2023).\n\nNilles and colleagues published a fascinating review on comorbid developmental stuttering (childhood-onset fluency disorder) and TS. Tics and stuttering are the most common ‘habit disorders’. They both have a male predominance and can significantly alter quality of life. Also, they both fluctuate and often go into remission after childhood. Of note, as clinicians seeing individuals with TS know, there are speech-blocking or stuttering-like tics that can be difficult to distinguish from developmental stuttering. More work disentangling the similarities and differences between both disorders is needed (Nilles et al. 2023b).\n\nStereotypies are the major hyperkinetic movements disorders associated with tics during the developmental period, and also a major differential diagnosis. Cavanna and colleagues presented a systematic literature review on comorbid tics and stereotypies based on six original studies that were deemed of sufficient quality and size. 23% of patients diagnosed with stereotypies had comorbid tics; conversely, the prevalence of stereotypies in individuals with TS was estimated at 8%. Interestingly, the authors point out the possibility that treatment-refractory repetitive movements in adults with TS could represent persistent stereotypies (Cavanna et al. 2024).\n\nGenetics and epigenetics\n\nIn 2023 three studies analyzed rare variants in TS. First, Saia and colleagues performed Array-CGH analysis of 93 phenotypically well-characterized TS cases to explore if the presence of pathogenic copy number variants (CNVs) was related with frequent clinical features. They investigated incidence of dysmorphic features, epilepsy, brain magnetic resonance imaging (MRI) anomalies, intellectual disability, and severity of symptoms in children with TS. They classified the CNVs as potentially causative variants (PC-CNVs) if they were reported to be associated with TS in the OMIM database, and as non-causative CNVs (NC-CNVs) if there was no previous association with TS reported or if they were of unknown significance. They performed statistical analyses to compare children with PC-CNVs, NC-CNVs and without CNVs (W-CNVs), and detected significant differences among the three groups for the occurrence of epilepsy or isolated EEG anomalies, brain MRI anomalies, intellectual disability and IQ (Saia et al. 2023).\n\nAnother study focusing on rare variants was performed by Fincha and colleagues. They performed a co-segregation analysis on 17 multiplex families including 80 TS or tic disorders patients and 44 healthy members. They prioritized 37 rare and possibly pathogenic variants shared by the cases within a family, and three ultra rare variants in two families. These variants are located in multiple genes and the majority of them on introns (Fichna et al. 2023).\n\nTsetsos and colleagues performed the largest Tourette Syndrome GWAS meta-analysis to date with a total of 6,133 TS cases and 13,565 controls, including a novel dataset. The increased sample size provided power to detect a novel genome-wide significant locus on chromosome 5q15, upstream of the NR2F1 gene. This locus was also supported by analyses combining eQTL, Hi-C and GWAS data. NR2F1 is a nuclear receptor that is a regulator of transcription. Additional analyses exploring the association of TS polygenic risk score with brain volume data revealed statistically significant associations with right and left thalamus volumes and right putamen volume (Tsetsos et al. 2023).\n\nJain and colleagues (2023) used TS GWAS summary statistics from Tsetsos and colleagues (Tsetsos et al. 2023) to calculate the TS Polygenic Risk Score (PRS) on individuals in the UK Biobank and then performed a Phenome Wide Association Study (PheWAS) to assess the association of TS genetic risk with a wide range of phenotypes (n=2242). They identified significant associations with 57 traits including depression, anxiety disorder, respiratory conditions, type 2 diabetes and heart palpitations. They also performed cross-disorder comparisons of the PheWAS results with OCD, ASD, and ADHD. The study identified shared associations with multiple health and behavioral phenotypes. TS had similar direction of effects for almost all phenotypes with ASD and ADHD, but OCD had an opposite direction of effect compared to TS (for all phenotypes except mental health traits). Then, they performed sex-specific PheWAS for TS, and they found heart palpitations and type 2 diabetes to be significantly associated with TS risk in males but not in females, while diseases of the respiratory system were associated with TS risk in females but not in males.\n\nWang and colleagues explored the rare maternally-inherited variants on X chromosome in simplex autism families extending their findings also to TS. First, they identified risk-enriched regions (RERs) using microarray data, and then they used whole-exome sequencing data to explore the rare maternally-inherited damaging variants in autism followed by transmission disequilibrium test which pointed to novel autism risk gene, MAGEC3. They applied the same framework to TS and ADHD male probands, and they observed that both traits were enriched for rare damaging variants in RERs, with similar effect sizes to autism. Finally, they estimated that 27.54% of the rare damaging variants carry risk for TS, with similar percentages for the other two traits (Wang et al. 2023).\n\nHughes and colleagues used genetic data and measures of psychopathology from Adolescent Brain Cognitive Development (ABCD) and Generation R, as replication, cohorts to explore the relationships of eight psychiatric disorders and cross-disorder Polygenic Scores (PGSs) to dimensional psychopathology in mid-childhood. They observed that the latent neurodevelopmental (NDV) factor PGS, which included loadings from ADHD, autism spectrum disorder, major depressive disorder, and TS, explained more variance across the spectrum of psychopathology than any other disorder-specific or cross-disorder PGS. They also performed gene-based association tests to define the NDV enriched genes (n=68) that were then included in downstream analyses to explore the pathways affecting the risk for childhood psychopathology. The gene ontology (GO) enrichment analysis of these genes did not return any significant results after FDR correction, however tissue expression showed that they were more strongly expressed in the cerebellum followed by cerebral cortical and subcortical regions. Gene expression analysis within the cerebellum from postmortem fetal and postnatal brain tissue, showed that the NDV genes (N = 68) were expressed significantly more strongly prenatally (Hughes et al. 2023).\n\nJiang and colleagues (Jiang et al. 2023) performed a two-sample Mendelian Randomization study to explore the causal relationships between plasma phosphodiesterases and psychiatric disorders, including TS. In the analysis for TS they used GWAS summary statistics from Yu and colleagues (Yu et al. 2019), and they observed a positive association of PDE5A with TS, while PDE2A was negatively associated with TS, however for both cases the associations were almost at nominal level.\n\nMahjani and colleagues utilized the Swedish Medical Birth Register to explore the direct additive genetic effect, genetic maternal effect and environmental maternal effect on CTD liability. They identified 6227 individuals with CTD diagnosis and by applying generalized linear mixed models they observed 60.7% direct additive genetic effect, 4.8% genetic maternal effect and 0.5% environmental maternal effect (Mahjani et al. 2023).\n\nNeurophysiology\n\nIn 2023, a few studies used EEG to assess brain connectivity patterns in individuals with TS. Jurgiel and colleagues investigated the additive and interactive effects of TS and ADHD on effective connectivity in children (Jurgiel et al. 2023). They reported additive effects of aberrant effective connectivity in TS and ADHD spanning several frequency bands. Aberrant effective connectivity was mostly found in children with ADHD, who showed reduced effective connectivity across several posterior and occipital-frontal connections. TS was associated with increased connectivity from the left postcentral to the right precuneus and reduced connectivity from the left occipital cortex to the right precuneus. Another EEG study, which was conducted in adults, assessed functional connectivity within and across nodes of the default mode network (Yang et al. 2023). They found increased beta-band connectivity between the left and right posterior cingulate/retrosplenial cortices, relative to controls. Also, using graph theoretical metrics, they found enhanced gamma-band degree centrality in the left temporal lobe, which was significantly correlated with increased tic severity.\n\nTwo EEG studies have investigated proactive control and binding processes in TS (Wehmeyer et al. 2023; Wendiggensen et al. 2023). In the first study, EEG markers of proactive control and binding were recorded during a cued task switching paradigm in adults with TS (Wehmeyer et al. 2023). After temporal decomposition, they found an absence of N2 modulation but increased P3 for repeated responses on task switch trials in the C-cluster, which includes intermediate processes between stimulus and response. In the second study, a S1-S2 paradigm was used to assess binding processes in adolescents and adults with TS (Wendiggensen et al. 2023). Their analyses, which focused on the theta frequency band, revealed that action file binding effects in the control group relied on the superior parietal regions cortex and the precuneus, whereas the superior frontal gyrus was involved in individuals with TS. Of note, both studies support the idea that integration of action in individuals with TS involves different neurophysiological processes, relative to controls.\n\nTo test whether altered social behaviors in TS reflected an overactive mirror neuron system, Weiblen and colleagues investigated mu suppression during an empathy for pain task in adults with TS (Weiblen et al. 2023). Mu suppression is thought to reflect empathic abilities and could serve as a marker of mirror neuron system function. During the experimental task, participants viewed pictures of hand and feet in neutral or painful situations. Study results revealed that adults with TS showed reduced pain-related mu suppression relative to controls, suggesting altered processing of others’ emotional states.\n\nTriggiani and colleagues assessed the sense of volition and the neural antecedents of tics and voluntary movements using a Libet’s clock paradigm (Triggiani et al. 2023). They asked adults with TS and controls to take note of the time they had the conscious intention to move and the time when they felt the initiation of a voluntary movement. However, groups did not differ on those measures. Those with TS were also asked to judge the timing of the intention and the initiation of tics, but those did not differ from the timing of voluntary movements. While most adults with TS showed a Bereitschaftspotential prior to tics, beta desynchronization was absent in a majority of individuals, suggesting dissociation between both processes. Furthermore, as commented by Gunduz and Ganos, the absence of beta desynchronization prior to tics could possibly help in distinguishing primary tics from functional tic-like behaviors (Gunduz and Ganos 2023).\n\nOther electrophysiological studies aimed to investigate motor cortical inhibition using transcranial magnetic stimulation. Consistent with previous findings (Larsh et al. 2023b), Batschelett and colleagues found no difference between children with TS and controls in terms of motor cortex short-interval cortical inhibition (Batschelett et al. 2023). However, short-interval cortical inhibition was significantly associated with increased tic severity. Schmidgen and colleagues used transcranial magnetic stimulation to evoke the N100 event-related potential, a marker of motor cortical inhibition thought to reflect GABAB receptors functioning (Schmidgen et al. 2023). They found reduced modulation of N100 by external (different stimulation intensities) and internal (different motor states: movement preparation and execution) modulation in children with TS. These results suggest altered modulation of motor cortical inhibition in TS, which would be related to GABAB processes.\n\nNeuroimaging studies\n\nOne of the most noteworthy neuroimaging studies of the last year was conducted by Zouki and colleagues (Zouki et al. 2023). Similar to a study published the preceding year (Ganos et al. 2022), they combined both lesion-network mapping (derived from cases associated with tic-inducing lesions) and resting-state functional networks obtained in patients with TS. While the precise anatomical localization of the lesions did not reveal a singular site related to tics, the network-based analysis highlighted a neural network implicating the posterior putamen, the caudate nucleus, the globus pallidus externus, and the precuneus. As a second level analysis, this network was found to be functionally disconnected in TS patients with a specific cluster identified in the right frontal white matter and cingulate gyrus. As highlighted in the accompanying scientific commentary (Ganos and Horn 2023), the robustness of these findings underscores their potential translation into clinical practice, offering promising avenues for the development of targeted therapeutic interventions.\n\nA second notable study, conducted by Kanaan and colleagues (Kanaan et al. 2023) was of particular interest. Focusing on the role of iron, the researchers compared quantitative susceptibility mapping and serum ferritin levels (both indicators of brain iron content) between 28 individuals with TS and 26 healthy controls. The findings yielded several significant insights: 1) A notable reduction in iron content was observed in TS in the substantia nigra, subthalamic nucleus, striatum, pallidum and dentate nucleus; 2) Interestingly, the severity of tics exhibited a correlation with serum ferritin levels; 3) Further analysis of gene expression patterns revealed associations between iron levels and neurochemical signalling, mitochondrial processes and phosphorylation-related mechanisms. This study is one of the first to highlight the role of iron in TS.\n\nA third research of interest compiled several metrics of functional connectivity based on three different approaches: the classic static functional connectivity, the dynamic one obtained with a sliding window, and independent component analysis (ICA) based connectivity (Ramkiran et al. 2023). Altogether, and by compiling a large variety of statistical metrics and analyses, the authors underscored the particular significance of metrics obtained with the dynamical approaches, especially related to networks involving the primary motor cortex, the prefrontal-basal ganglia pathway and the amygdala.\n\nTwo other studies of interest were conducted on children with TS. One study (Hsu et al. 2023) investigated microstructural changes, while the other (Xin et al. 2023) examined alterations in dynamic brain functional networks. The first study (Hsu et al. 2023) compared two cohorts comprising 30 individuals each (healthy controls versus individuals with pure and treatment-naïve TS). Utilizing diffusion spectrum imaging metrics, with a specific focus on the cortico-striato-thalamocortical network, the authors did not observe any significant alterations in several segments of the network, but they identified that TS was associated with elevated generalized fractional anisotropy in the right frontostriatal tract (which also correlated with tic severity) and in the bilateral thalamic radiation. In the second study (Xin et al. 2023), temporal properties of functional connectivity were assessed by comparing 36 male individuals with TS to 27 matched healthy controls. Notably, a dysfunctional functional state was identified in TS, correlating with tic severity. This state was characterized by over-connection within the subcortical, sensorimotor, and default mode networks, coupled with under-connection in the salience and executive control networks. Additionally, TS was associated with higher temporal variability in functional networks compared to controls. Although employing different methodologies, both studies converged to underscore the dysfunction of the basal ganglia in TS, thereby enriching our comprehension of brain functioning in children with the disorder.\n\nFinally, using tractography in 58 TS patients and 35 healthy volunteers, Temiz and colleagues showed a significantly increased limbic cortical connectivity in TS patients (Temiz et al. 2023). In particular, connectivity of the left insular-subthalamic nucleus was positively correlated with higher impulsivity and anxiety scores.\n\nAnimal models\n\nTS pathophysiology has been linked to a disturbed migration of cholinergic interneurons into the striatum (Kataoka et al. 2010), disturbed dopaminergic transmission (Maia and Conceição 2018), and, in rare monogenetic forms, a loss-of-function in the SLITRK1 gene (Abelson et al. 2005). Du and colleagues attempt to link all three in a mouse model where SLITRK1 si-RNA was injected into the dorsal striatum, and they observed a number of behavioral, neurochemical and electrophysiological abnormalities compatible with TS in humans. They conclude that targeting the function of striatal cholinergic interneurons might represent as a potential therapeutic strategy for TS (Du et al. 2023).\n\nPsychological interventions\n\nTreatment guidelines published by the American Academy of Neurology (AAN) (Pringsheim et al. 2019) and the European Society for the Study of Tourette Syndrome (ESSTS) (Müller-Vahl et al. 2022) recommend behavior therapy (BT) as the first-line intervention for TS/CTD. Several modalities of BT are currently available, of which Habit Reversal Training (HRT) and its extended form Comprehensive Behavioral Intervention for Tics (CBIT) has the strongest evidence base. Comparatively less support is available for Exposure and Response Prevention (ERP), but this BT modality remains popular among many clinicians and researchers – especially in Europe.\n\nConelea and colleagues initiated a project involving researchers, clinicians, patients, and families with the aim to identify future priorities for research of BT for TS/CTD (Conelea et al. 2024). Key research domains were identified through anonymous community surveys. One of these domains concerned the importance of increasing accessibility to BT for patients. Similar to recent years, dissemination of BT has been a recurring theme in TS/CTD research also in 2023. One way of making BT more available is by using a group format, thereby reducing the needed therapist support compared to a regular in-person format. Bekk and colleagues published an open study of 26 participants (20-70 years) using group-delivered CBIT in Norway, the first of its kind in an adult sample (Bekk et al. 2023). The results showed a large, significant, mean tic severity improvement (YGTSS-TTS) from baseline to a 1-year follow-up (d=1.20). The resources saved in this particular study may however be questioned given that two therapists were present at all times and that each session lasted 180 minutes (about three times longer than the average in-person session as instructed in the manual by Woods and colleagues (Woods et al. 2008). In an open study conducted in the UK, Hadjii-Michael and colleagues evaluated an intensive group delivery protocol of ERP (Hadji-Michael et al. 2024). Twenty young participants (8-16 years) with TS or CTD were recruited and received ERP according to the manual by Verdellen and colleagues (Verdellen et al. 2011), although intensively delivered (3 days + 1 booster day, compared to 12 weekly 1-hour sessions). Results showed a moderate, significant, mean tic severity improvement (r=0.48), suggesting that intensive group-ERP is preliminarily efficacious. Another delivery format with the potential to increase accessibility to BT is videoconferencing. In an open study by Capriotti and colleagues (Capriotti et al. 2023), 19 youth and 10 adults received CBIT according to the manual by Woods and colleagues (Woods et al. 2008), albeit via videoconferencing and without booster sessions. Results showed a large, significant, tic severity improvement (YGTSS-TTS) from baseline to post-treatment for youth (d=1.31) and a medium-sized improvement for adults (d=0.66), further adding to the evidence-base for this delivery format. Lastly, internet-delivered BT with therapist-support has been a popular delivery format in recent years. In a long-term follow-up of the ORBIT trial conducted in the UK (N=224) (Hollis et al. 2023), internet-delivered ERP was shown superior to internet-delivered psychoeducation all through to a follow-up 18 months post-randomization, although with a small effect size at the this last follow-up timepoint (d=0.27). An additional health economic evaluation showed ERP to be cost-effective compared to psychoeducation. Taken together, this study shows that internet-delivered ERP is an efficacious, cost-effective, and durable intervention, although the small effect size may indicate inferiority to in-person BT.\n\nAnother domain identified by the survey conducted by Conelea and colleagues was ways to improve treatment outcomes, which in turn may be linked to identifying the underlying working mechanisms of BT (Conelea et al. 2024). A proposed working mechanism of BT is within-session habituation to aversive sensations preceding tic occurrence (i.e., premonitory urges). In a Dutch study by van de Griendt and colleagues (van de Griendt et al. 2023), 29 participants with TS (7-59 years) rated premonitory urge intensity at multiple timepoints during 10 in-person ERP sessions. Results showed an increased urge intensity during the first 15 minutes of each session, which then levelled out during the remaining 45 minutes of the session. The authors concluded that the study did not provide support for within-session habituation as a working mechanism for ERP. In a mechanistic study by Morand-Beaulieu and colleagues (Morand-Beaulieu et al. 2023a), electroencephalography (EEG) was used to collect data on 32 children (8-13 years) participating in an RCT comparing in-person CBIT to a treatment-as-usual condition. Based on another recent study conducted in an experimental setting where the same group identified a brain network in which functional connectivity was increased during tic suppression in children with TS (Morand-Beaulieu et al. 2023b), the current study aimed at testing whether the same network was involved in treatment response to in-person CBIT. The results showed that functional connectivity during tic suppression at baseline predicted a reduction in vocal tic severity at post-treatment. To conclude, this study provided evidence for a potential overlap between the working mechanisms of tic suppression when used in an experimental setting compared to a clinical setting.\n\nPharmacological studies\n\nTo date, no compound has been specifically marketed for the treatment of tics. Ecopipam, a selective D1 receptor antagonist, might be one of the first drugs to be commercialized for this purpose. After two first proof of principle studies (Gilbert et al. 2014; Gilbert et al. 2018), Gilbert and colleagues have now published the results of a phase 2b trial (D1AMOND study) in individuals with TS (Gilbert et al. 2023). Seventy six patients were randomized to ecopipam and 77 to placebo. Total tic scores as assessed by the YGTSS were significantly reduced (by around 30%) in the ecopipam group, as well as secondary outcome measures. Importantly, no metabolic side effects were reported. A phase 3 trial is now underway (NCT06021522).\n\nThe results of the CANNA-TICS study appeared in early 2023 (Müller-Vahl et al. 2023). The authors performed a randomized, controlled trial of nabiximols in 97 adults with TS or chronic motor or verbal tic disorder. Befitting the study investigators’ a priori view of the literature, people were randomized to drug or placebo in a 2:1 ratio. The primary, predefined efficacy endpoint was a tic reduction of at least 25% on the YGTSS total tic score after 13 weeks of treatment, a magnitude of change recognized as clinically meaningful improvement by an expert panel. The study did not show significant improvement by this measure. However, there were some indications of improvement, including a higher response rate (22% vs 9%) in the nabiximols group, a significantly greater reduction in self-reported tic severity on the Adult Tic Questionnaire, a numerically greater improvement of tics on a standardized video rating scale, and trends for improvement in quality of life and in impairment due to tics. There were no serious safety issues, with side effects of similar severity in 95% of those in the active drug group versus 79% of those in the placebo group (p=.03). Patients with ADHD or with worse general health were most likely to improve. Thirteen percent of patients at the site that enrolled over half the participants reported intentional or accidental unblinding on an end-of-study interview. Of course, other participants likely suspected their drug assignment; a forced-choice blindedness assessment is not reported. In sum, a reasonably large RCT showed hints of superiority for nabiximols over placebo, but the study did not meet the pre-specified treatment target. The authors are to be commended for timely publishing a technically negative study, but one with important clinical implications. In contrast to the findings of the previous study, a small cross-over RCT (N=22) showed significantly more improvement in tics with a THC + CBD combination than with placebo, YGTSS decrease being 8.9 (±7.6) in the active group and 2.5 (±8.5) in the placebo group (Mosley et al. 2023). The main side effects were cognitive/sedative in nature.\n\nA 2-year naturalistic study with 1,410 participants (1,147 with ADHD, the rest without ADHD) provided important information relevant to the safety of methylphenidate (MPH) in tic patients (Man et al. 2023). Their main goal was to see if the stimulant, which suppresses appetite, suppressed growth. There was no significant difference in growth among children in or out of the MPH group. Blood pressure and pulse were significantly higher in the MPH group, but only trivially (about 1 mm Hg and 1 beat per minute after correcting for baseline differences). Tic prevalence decreased significantly in all 3 groups, more in the ADHD groups. There was slightly less tic improvement at 12 months in the group taking MPH (< 2 points on the YGTSS) but no significant difference at 6 months. Note that randomized, placebo-controlled studies show that tics actually improve, on average, on MPH (Black 2023). In summary, MPH is relatively safe in ADHD, including in those with tics.\n\nNeurosurgery\n\nSeveral notable papers were published this year about deep brain stimulation (DBS) in TS. Rusheen and colleagues investigated the effect of centromedian (CM) thalamic DBS on modulating dopamine activity in the dorsomedial striatum, using a comprehensive approach combining electrophysiology, electrochemistry, optogenetics and behavioural measurements (Rusheen et al. 2023). They found that CM DBS evoked synaptic dopamine release and elevated tonic dopamine levels via striatal cholinergic interneurons, while inactivation of D2 receptors reduced clinical response. This pivotal study suggests that tic improvement with thalamic DBS is partially mediated by D2 receptor activation, providing further evidence of the involvement of dopamine dysfunction as a crucial factor for motor tics in TS.\n\nThere is ongoing debate around the most relevant target for DBS in TS, the commonly accepted view being that different structures within a common basal ganglia-thalamo-cortical network may serve as potential targets. In a retrospective study using MRI tractography in 21 patients, Avecillas and colleagues investigated the basal ganglia-thalamo-cortical networks associated with tics and obsessive compulsive behaviors (OCB) improvement in patients treated with either anteromedial globus pallidus (amGPi) or thalamic ventral-oralis complex/centromedian (Vo/CM) DBS (Avecillas-Chasin et al. 2023). The networks associated with clinical improvement of tics consisted of a limbic pallidothalamic network for the amGPi target, and the premotor thalamocortical network for the thalamic target, both of which being part of a larger “limbic-motor interface network”. Notably, analysis of the volume of tissue activated by DBS in non-responders showed that the stimulation missed the tracts associated with this specific network. This study reinforces the idea that stimulating this network either at its origin (amGPi), or terminal fields (Vo) can lead to substantial tic improvement. Improvement in OCB was related to the connectivity between the dorso-medial prefrontal cortex (dmPFC)/dorsal anterior cingulate (dACC) and CM. The fact that tics and OCB improvement may be linked to the stimulation of distinct networks questions the relevance of targeting more than one structure.\n\nNajera and colleagues reported on two patients with severe GTS and OCD who underwent dual-targeting DBS in both the ventral capsule/ventral striatum (VC/VS) for OCD, and posteroventral GPi for tics (Najera et al. 2023). Both patients experienced sustained improvement in both tics and OCB.\n\nFor the first time, a study explored the relationship between the microlesion effect and the anatomic location of implanted DBS leads in the CM nucleus of the thalamus (Morishita et al. 2023). The microlesion effect refers to the immediate improvement of symptoms after lead implantation and is considered to result from edema, microhemorrhage, and/or the disruption of fibers along the trajectory of the electrodes. All 6 patients with TS included in this study experienced tic improvement related to microlesion effect. Connectivity analyses showed connections between the area related with microlesion effect and the prefrontal cortices and globus pallidus.\n\nThe team of Vilela Filho and colleagues has previously suggested that clinical symptoms of TS may be linked to hyperactivity of the globus pallidus externus (GPe), based on animal models and theoretical models of the basal ganglia. In this recent paper, they report for the first time the results of an open clinical trial of GPe stimulation in TS patients (Vilela-Filho et al. 2023). They found that 10 of the 13 patients responded to surgery (mean global improvement in tics of 64%, mean improvement of OCB 57.8%). They also found significant improvements in depression and anxiety scores. These promising results of GPe DBS remain to be replicated in future studies. Interestingly, they also reported on 2 patients who continued to have excellent tic improvement despite battery depletion, while another patient experienced severe rebound effect. Another case report of a patient with Centromedian/Parafascicular (Cm/Pf) stimulation who experienced severe tic status following battery depletion was published this year (Parmera et al. 2023). The mechanisms of these ongoing responses or rebound effects remain to be deciphered.\n\nLee and colleagues published a new study involving 20 patients who underwent DBS of the amGPi (Lee et al. 2023). Interestingly, they employed quite unusual stiumulation parameters with lower frequency (around 80 Hz), and higher pulse width (around 120 μs) than commonly used. At 1 year, 60% of patients had a >35% reduction on the on the YGTSS. Initial response appeared to predict improvement on the YGTSS at one year, and the effect at 12 months was more pronounced than at 3 months.\n\nOther treatments\n\nIncreased activity in the left inferior parietal cortex (BA40) appears to be involved in the generation of tics. However, inhibitory repetitive transcranial magnetic stimulation (rTMS) compared to sham and applied to the left prefrontal cortex (BA 40) in 29 adults with TS showed no evidence of benefit on tics (Paulus et al. 2023).\n\nTwo randomized, controlled trials of median nerve stimulation (MNS) for treatment of tics appeared in 2023, following up on the fascinating initial report by Morera Maiquez and colleagues in 2020 (Morera Maiquez et al. 2020). The first was an in-laboratory crossover trial comparing repeated 1- or 5-minute sessions of 10 or 12 Hz stimulation in 32 people with a CTD (Iverson et al. 2023). Rhythmic MNS was given on one day for repeated stimulation-on and -off, 1- and 5-minute blocks, and arrhythmic MNS at the same mean frequency on another day. Either produced significant improvement in tics and premonitory urges, to a similar degree. Since only rhythmic stimulation increases contralateral sensorimotor cortex 12 Hz activity on EEG (Morera Maiquez et al. 2020) or MEG (Houlgreave et al. 2022), those effects do not reflect the mechanism of the clinical benefit.\n\nThe second MNS controlled trial was a home-based parallel-group study of a wristwatch-style stimulation device (Morera Maiquez et al. 2023). The active treatment (N=45) used unilateral 10 Hz MNS at a current just above the threshold for activating movement of the thumb. A sham condition (N=45) was MNS that began at the same current as the active treatment, but current was smoothly decreased by about half over the next minute. Both treatments were given for a total of 10 minutes (5 blocks of 2 min on, 1 min off) every morning for 4 weeks. Both treatments activated sensory nerve fibers, and participants were adequately blinded. A third, wait-list condition (N=45), was meant to measure the magnitude of the placebo response in the sham treatment group. During MNS, active treatment was superior to sham MNS and to wait-list controls, and interestingly, the latter two groups had approximately equal responses. Surprisingly, even though stimulation was only on for 10 minutes a day, clinical response “offline,” i.e., YGTSS rated over the entire past week, was also clearly more effective with active MNS.\n\nWillford and Deeb published a scoping review on multidisciplinary care in TS. Thirty one articles were considered. Four primary benefits of multidisciplinary care were identified, making it the preferred model advocated by patients, physicians and organizations to improve clinical outcome. However, limitations to this approach and to this approach and lack of empirical evidence were also highlighted (Willford and Deeb 2023).\n\nTreatment for tic-like functional symptoms\n\nRecent years have seen a considerable increase in patients displaying FTLBs, rather than tics as in TS or CTD. Even though researchers have agreed on how these symptoms may be differentiated from tics (Pringsheim et al. 2023), little is published on how functional tic-like behaviors may be treated. In an Australian case series published by Maxwell and colleagues (Maxwell et al. 2023), 8 participants (13-20 years) with functional tic-like behaviors received an adapted CBIT intervention. The adaptations included added components from third-wave CBT, with the aim to target both the tic-like symptoms and potential underlying (and triggering) stress. Overall, cases showed large tic severity reductions (YGTSS-TTS) from baseline to post-treatment, indicating preliminary support for the intervention. Larger and controlled studies are warranted.\n\nPring and colleagues reviewed the topic of stigma in TS (Pring et al. 2023). Evidence from 47 publications showed lower self-esteem in youth TS/CTD, who experienced more frequent bullying and other kinds of peer abuse. The community environment contributed, including school and work settings and the general public.\n\nKnowledge of TS among teachers was assessed in a study by Sapozhnikov and colleagues (Sapozhnikov et al. 2023). Differences in knowledge on TS, self-perceived understanding and use of sources of information were examined in 144 teachers of children with TS and 78 teachers of control subjects, using the pilot questionnaire Teacher Understanding of Tourette Syndrome Survey (TUTS). Teachers of children with TS had higher self-perceived understanding, more knowledge, and used more sources of information compared to the teachers in the control group.\n\nStacy and colleagues gathered information on perceptions about TS among physicians and caregivers and compared the attitudes between different specialists (neurologists, psychiatrists) and caregivers. While physicians consider pharmacotherapy even when tics are slightly bothersome, caregivers have a preference for behavioral interventions (Stacy et al. 2023).\n\nFletcher and colleagues evaluated the professional development needs of health care professionals regarding TS (Fletcher et al. 2023). As a result, healthcare workers reported urgent need to have access to evidence-based webinars and materials about TS and OCD. While 80% of participants had patients with TS and/or OCD in their practice, only 50% had any formal training in this area. As part of the TS OCD Alberta Network, a program consisting of twelve online webinars was delivered.\n\nDiagnostic accuracy in determining tic diagnosis was explored by a group from South Korea (Sung and Hong 2023). They found that in the vast majority of cases (96.5%), diagnoses of different tic disorders were made correctly.\n\nThe International Parkinson’s Disease and Movement Disorders Society Tic and Tourette Syndrome Study Group formed a subcommittee to discuss further barriers to practice guideline implementation among clinicians treating patients with tics (Martindale et al. 2023). The following barriers were identified: accessibility to specialized care, financial costs or coverage of treatment, neuropsychiatric comorbidities, treatment side effects, and stigma of the disease.\n\nMarino and colleagues explored patients’ experience of accessing support from primary care physicians in the UK (Marino et al. 2023). Altogether, more negative than positive experiences were reported. Main areas of frustration included lack of exploration of tics or no psychoeducation. Around 20% of participants had problems to get a referral to a specialist. When it comes to specialized care, adults were mainly seen by neurologists, while children mainly were treated by psychiatrists or pediatricians. Only 28% of patients were seen by physicians specialized in tic disorders. The average waiting time for children was 3-6 months but it was much longer for adults. One fifths of people was discharged from the clinic without further support, while 30% reported support by private healthcare.\n\nIn “‘No ill will’: Ticcing on Moral Grounds” Curtis-Wendlandt, argues that tics are less blameworthy than other intentional actions, but are often misconstrued as morally salient behaviours (Curtis-Wendlandt 2023). Bervoets and colleagues published an interesting viewpoint following similar lines of thought and inviting more inclusive patient-based perspective (Bervoets et al. 2023).\n\nColeman and Melia investigated the topic of self-identity in females with TS. The methodology was a focused semi-structured interview conducted via Zoom (Coleman and Melia 2023). Five themes were established: “I’m not normal”, “I just want to be me”, I’m a “people pleaser”, seeing oneself as an “outsider”, and “it’s just part of me … it’s not going anywhere”. Difficulties with self-acceptance and the autonomy to be one’s true self were noted and appeared to be intensified by stereotypical gender roles and attempts to conceal tics. Findings also suggested that personal growth and feelings of mastery can be achieved through embracing TS as part of one’s identity, or recognizing it as just one aspect of the self. Psychological support focused on accepting and living with tics rather than reducing them may benefit this population and is currently difficult to access. Consideration should also be given to improving the availability of support groups where women with TS can meet others like themselves.\n\nAn interesting topic of moral decision making in patients with TS was explored by Vicario and colleagues (Vicario et al. 2023). The authors found higher inclination for utilitarian solutions of moral dilemmas in patients with TS. Of note, TS individuals had more tendency to quantify something as morally wrong or right. The authors concluded that there might be neurobiological correlates of inappropriate behaviors in people with TS that could be an underlying cause of the higher utilitarian moral decision-making.\n\nWellen and colleagues investigated health care experiences among a sample of caregivers of children with tic disorders using a survey (Wellen et al. 2023). They found that the majority (70%) of families first consulted their pediatrician/primary care provider, and caregivers reported receiving care in line with current best practice guidelines. However, caregivers in the current sample also perceived a lack of knowledgeability on the part of their first providers.\n\nThe topic of stigma and TS was raised by Shiu and colleagues (Shiu et al. 2023). The authors identified three types of enacted stigmas: traumatic events, confrontations, and subtle mistreatments. While traumatic events were associated with tic severity, subtle mistreatments contributed to impairment of quality of life.\n\nLund and colleagues investigated the impact of TS on education (Lund et al. 2023). This was a longitudinal study to assess the educational achievements at different timepoints. Overall, children with TS had a lower passing rate at lower secondary school and high school compared to healthy controls. These disparities were more likely driven by the severity of comorbidities than tic severity.\n\n\nConclusions\n\nThis is the tenth yearly article in the Tourette Syndrome Research Highlights series. We began this project to highlight top research reports from the past year relevant to TS. Remarkably, one third of all the literature on TS has appeared in just these ten years (see Figure 1). The pace of new research makes it increasingly hard to keep up, and our annual highlight article is getting more voluminous by the year.\n\nOne third of these (2 669) have appeared in the past 10 years.\n\nNew reports this year described important advances in several areas. Increasingly, data have appeared to clarify the phenomenon of functional tic-like symptoms: exactly how they differ from typical tics in TS, their prognosis, and their treatment. Methods for automated detection and timing of tics are progressing steadily and when ripe are likely substantially to aid both research and treatment. Prospective studies of tic outcome continue to be important. The relationship of tics with an urge to tic and sensory phenomena continues to be clarified, along with their electrophysiological substrates. Genetic studies are gradually accruing the large sample sizes required for identifying tic-related genes with small effect sizes. Several EEG studies applied new approaches to study tics.\n\nHighlights within the highlights include new treatments for tics that have not yet made it into the clinic but offer hope they will. One includes median nerve stimulation using a portable device (wristband) which would also be the first on-demand treatment of tics (Morera Maiquez et al. 2023). On the pharmacological aisle, we see the dopamine D1 antagonist ecopipam emerging as the first drug developed specifically for the treatment of tics, with a favorable side effect profile compared to D2 receptor antagonists when it comes to metabolic side effects (Gilbert et al. 2023). Then, we see studies refining the neuroanatomy and connectivity of TS based on sophisticated neuroimaging approaches and deep brain stimulation treatments (Zouki et al. 2023). Finally, there is still a substantial literature on FTLB with interesting relations to classic, neurodevelopmental tics that can frequently co-occur, complicating diagnosis and treatment to a certain extent (Müller-Vahl et al. 2024).\n\nThe field seems ripe for additional work in several areas. A number of important questions about tic disorders remain mysterious, and future work may clarify them: Why do tics start around age 5-10 years? Why are boys more likely to develop tics? How accurately can we predict outcomes for individual patients? Why do tics improve during sleep, or with the transition to adolescence and adulthood? Can we identify a natural non-human animal model? Do neurosteroids reduce tics in humans? Which patients need which treatments?\n\nSeveral areas cry out for new research. The nosology of tic disorders has been driven by historical separations such as whether tics involve muscles of respiration and phonation, or whether tics have been present for 12 months. One can hope for development and acceptance of a more science-based nosology. Acceptance and Commitment Therapy, or other newer behavior therapies that avoid focusing on tic suppression, may be better accepted by patients. Tic disorder therapies have thus far been primarily focused on symptom reduction, but with safe behavior therapies, it is time to consider tic prevention.\n\nWhere will the answers come from? Increasing large-scale collaborative studies, including prospective tic surveillance studies, may help bring answers to the clinical mysteries, genetic factors, and treatment development. Novel techniques, such as ex vivo organoids from induced pluripotent stem cells, may clarify pathophysiology. We are enthusiastic to see what the next decade brings.",
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PubMed Abstract | Publisher Full Text\n\nLee J, Chang KW, Jung HH, et al.: One-year outcomes of deep brain stimulation in refractory Tourette syndrome. Psychiatry Clin. Neurosci. 2023; 77: 605–612. PubMed Abstract | Publisher Full Text\n\nLewin AB, Murphy TK, Mink JW, et al.: Brief youth self-report screener for tics: Can a subscale of the Motor tic, Obsession and compulsion, and Vocal tic Evaluation Survey (MOVES) identify tic disorders in youth? Evid.-Based Pract. Child Adolesc. Mental Health. 2023; 8: 1–11. PubMed Abstract | Publisher Full Text\n\nLi Y, Yu L, Zhang H, et al.: The Severity and Neural Correlates of Premonitory Urge in Tourette Syndrome: A Systematic Review and Meta-Analysis. J. Integr. Neurosci. 2023; 22: 159. PubMed Abstract | Publisher Full Text\n\nLiu F, Wang G, Ye J, et al.: Sociodemographic and clinical characteristics of children with tic disorders and behavioral problems: A real-world study and development of a prediction model. BMC Pediatr. 2023; 23: 53. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLund J, Borch-Johnsen L, Groth C, et al.: Impact of Tourette Syndrome on Education. Neuropediatrics. 2023; 54: 107–112. PubMed Abstract | Publisher Full Text\n\nMüller-Vahl KR, Pisarenko A, Fremer C, et al.: Functional Tic-Like Behaviors: A Common Comorbidity in Patients with Tourette Syndrome. Mov. Disord. Clin. Pract. 2024; 11(3): 227–237. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMüller-Vahl KR, Pisarenko A, Szejko N, et al.: CANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders - Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study. Psychiatry Res. 2023; 323: 115135. PubMed Abstract | Publisher Full Text\n\nMüller-Vahl KR, Szejko N, Verdellen C, et al.: European clinical guidelines for Tourette syndrome and other tic disorders: summary statement. Eur. Child Adolesc. Psychiatry. 2022; 31: 377–382. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMahjani B, Klei L, Buxbaum GAS, et al.: Direct additive genetics and maternal effect contribute to the risk of Tourette disorder. J. Neurol. Neurosurg. Psychiatry. 2023; 94: 638–642. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaia TV, Conceição VA: Dopaminergic Disturbances in Tourette Syndrome: An Integrative Account. Biol. Psychiatry. 2018; 84: 332–344. PubMed Abstract | Publisher Full Text\n\nMalaty IA, Anderson S, Bennett SM, et al.: Diagnosis and Management of Functional Tic-Like Phenomena. J. Clin. Med. 2022; 11.\n\nMan KKC, Häge A, Banaschewski T, et al.: Long-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study. Lancet Psychiatry. 2023; 10: 323–333. PubMed Abstract | Publisher Full Text\n\nMarino C, Khan K, Groom MJ, et al.: Patients’ experience of accessing support for tics from primary care in the UK: an online mixed-methods survey. BMC Health Serv. Res. 2023; 23: 788. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMartindale JM, Sarva H, Martino D, et al.: Study protocol: A cross-sectional survey of clinicians to identify barriers to clinical practice guideline implementation in the assessment and treatment of persistent tic disorders. PLoS One. 2023; 18: e0288408. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMartino D, Hedderly T, Murphy T, et al.: The spectrum of functional tic-like behaviours: Data from an international registry. Eur. J. Neurol. 2023; 30: 334–343. PubMed Abstract | Publisher Full Text\n\nMataix-Cols D, Isomura K, Brander G, et al.: Early-Life and Family Risk Factors for Tic Disorder Persistence into Adulthood. Mov. Disord. 2023; 38: 1419–1427. PubMed Abstract | Publisher Full Text\n\nMaxwell A, Zouki JJ, Eapen V: Integrated cognitive behavioral intervention for functional tics (I-CBiT): case reports and treatment formulation. Front. Pediatr. 2023; 11: 1265123. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMorand-Beaulieu S, Crowley MJ, Grantz H, et al.: Functional connectivity during tic suppression predicts reductions in vocal tics following behavior therapy in children with Tourette syndrome. Psychol. Med. 2023a; 53: 7857–7864. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMorand-Beaulieu S, Wu J, Mayes LC, et al.: Increased Alpha-Band Connectivity During Tic Suppression in Children With Tourette Syndrome Revealed by Source Electroencephalography Analyses. Biol. Psychiatry Cogn. Neurosci. Neuroimaging. 2023b; 8: 241–250. PubMed Abstract | Publisher Full Text\n\nMorera Maiquez B, Sigurdsson HP, Dyke K, et al.: Entraining Movement-Related Brain Oscillations to Suppress Tics in Tourette Syndrome. Curr. Biol. 2020; 30: 2334–42.e3. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMorera Maiquez B, Smith C, Dyke K, et al.: A double-blind, sham-controlled, trial of home-administered rhythmic 10-Hz median nerve stimulation for the reduction of tics, and suppression of the urge-to-tic, in individuals with Tourette syndrome and chronic tic disorder. J. Neuropsychol. 2023; 17: 540–563. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMorishita T, Sakai Y, Iida H, et al.: Precision Mapping of Thalamic Deep Brain Stimulation Lead Positions Associated With the Microlesion Effect in Tourette Syndrome. Neurosurgery. 2023; 93: 875–883. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMosley PE, Webb L, Suraev A, et al.: Tetrahydrocannabinol and Cannabidiol in Tourette Syndrome. NEJM Evid. 2023; 2: EVIDoa2300012. Publisher Full Text\n\nNajera RA, Provenza N, Dang H, et al.: Dual-Target Deep Brain Stimulation for Obsessive-Compulsive Disorder and Tourette Syndrome. Biol. Psychiatry. June 2023; 93(11): e53–e55. PubMed Abstract | Publisher Full Text\n\nNilles C, Berg L, Fleming C, et al.: Developmental stuttering, physical concomitants associated with stuttering, and Tourette syndrome: A scoping review. J. Fluen. Disord. 2023b; 77: 105992. PubMed Abstract | Publisher Full Text\n\nNilles C, Martino D, Fletcher J, et al.: Have We Forgotten What Tics Are? A Re-Exploration of Tic Phenomenology in Youth with Primary Tics. Mov. Disord. Clin. Pract. 2023a; 10: 764–773. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNilles C, Szejko N, Martino D, et al.: Prospective follow-up study of youth and adults with onset of functional tic-like behaviours during the COVID-19 pandemic. Eur. J. Neurol. 2024; 31: e16051. PubMed Abstract | Publisher Full Text\n\nOkkels KB, Skov L, Klansø S, et al.: Increased Number of Functional Tics Seen in Danish Adolescents during the COVID-19 Pandemic. Neuropediatrics. 2023; 54: 113–119. PubMed Abstract | Publisher Full Text\n\nParmera JB, Yamamoto JYS, Cury RG: Tic Status in Tourette Syndrome Due to Depletion of the Deep Brain Stimulation Battery. JAMA Neurol. March 2023; 80(3): 320–321. PubMed Abstract | Publisher Full Text\n\nPaulus T, Wernecke L, Lundie A, et al.: The Role of the Left Inferior Parietal Cortex in Gilles de la Tourette Syndrome—An rTMS Study. Biomedicines. March 2023; 11(3): 980. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPrato A, Salerno AM, Saia F, et al.: Symptoms compatible with long COVID in an Italian pediatric cohort of Tourette patients with and without SARS-CoV-2 infection: a short-term follow-up assessment. BMC Pediatr. May 2023; 23(1): 222. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPring K, Malli M, Hardy BW, et al.: Reframing stigma in Tourette syndrome: an updated scoping review. Eur. Child Adolesc. Psychiatry. 2023. PubMed Abstract | Publisher Full Text\n\nPringsheim T, Ganos C, Nilles C, et al.: European Society for the Study of Tourette Syndrome 2022 criteria for clinical diagnosis of functional tic-like behaviours: International consensus from experts in tic disorders. Eur. J. Neurol. January 2023; 30(4): 902–910. PubMed Abstract | Publisher Full Text\n\nPringsheim T, Okun MS, Müller-Vahl K, et al.: Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019; 92: 896–906. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRamkiran S, Veselinović T, Dammers J, et al.: How brain networks tic: Predicting tic severity through rs-fMRI dynamics in Tourette syndrome. Hum. Brain Mapp. May 2023; 44(11): 4225–4238. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRaz G, Davidovitch S, Halevi M, et al.: Impact of movie and video game elements on tic manifestation in children. Eur. J. Neurol. 2024; 31: e16120. PubMed Abstract | Publisher Full Text\n\nRiechmann R, Jakubovski E, Essing J, et al.: The Rush Video-Based Tic Rating Scale-Revised: A Practice-Oriented Revision. Mov. Disord. Clin. Pract. 2023; 10: 802–810. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRigas A, Mainka T, Pringsheim T, et al.: Distinguishing functional from primary tics: a study of expert video assessments. J. Neurol. Neurosurg. Psychiatry. 2023; 94: 751–756. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRizzo G, Martino D, Avanzino L, et al.: Social cognition in hyperkinetic movement disorders: a systematic review. Soc. Neurosci. 2023; 18: 331–354. PubMed Abstract | Publisher Full Text\n\nRusheen AE, Rojas-Cabrera J, Goyal A, et al.: Deep brain stimulation alleviates tics in Tourette syndrome via striatal dopamine transmission. Brain. May 2023; 146(10): 4174–4190. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSadeh DF, Frenk ML, Simha T, et al.: Moderating Role of Depression on the Association of Tic Severity With Functional Impairment in Children. Pediatr. Neurol. 2023; 144: 90–96. PubMed Abstract | Publisher Full Text\n\nSaia F, Prato A, Saccuzzo L, et al.: Copy Number Variations in Children with Tourette Syndrome: Systematic Investigation in a Clinical Setting. Genes (Basel). 2023; 14.\n\nSapozhnikov Y, Mink JW, Augustine EF, et al.: Teacher Knowledge of Tourette Syndrome and Associated Factors. Pediatr. Neurol. 2023; 145: 80–87. PubMed Abstract | Publisher Full Text\n\nSchmidgen J, Konrad K, Roessner V, et al.: The external evocation and movement-related modulation of motor cortex inhibition in children and adolescents with Tourette syndrome – a TMS/EEG study. Front. Neurosci. October 2023; 17: 17. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShiu C, Chen WT, Kim B, et al.: The Roles of Lifetime Enacted Stigma in Tic Symptoms among Young Adults with Tourette Syndrome. Mov. Disord. Clin. Pract. 2023; 10: 1759–1768. PubMed Abstract | Publisher Full Text\n\nStacy S, Salinas GD, Belcher E, et al.: Assessing the educational needs of physicians in the management of patients with Tourette syndrome: results of a United States survey on practicing clinicians and caregivers - Corrigendum. CNS Spectr. 2023; 28: 387. PubMed Abstract | Publisher Full Text\n\nSung Y, Hong SB: Diagnostic Hierarchy of Tic Disorders in Real-World Clinical Practice. Soa Chongsonyon Chongsin Uihak. 2023; 34: 236–241. PubMed Abstract | Publisher Full Text\n\nSzejko N, Fletcher J, Martino D, et al.: Premonitory Urge in Patients with Tics and Functional Tic-like Behaviors. Mov. Disord. Clin. Pract. December 2023; 11: 276–281. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTemiz G, Atkinson-Clement C, Lau B, et al.: Structural hyperconnectivity of the subthalamic area with limbic cortices underpins anxiety and impulsivity in Tourette syndrome. Cereb. Cortex. 2023; 33: 5181–5191. PubMed Abstract | Publisher Full Text\n\nTriggiani AI, Scheman K, Pirio Richardson S, et al.: Physiological and introspective antecedents of tics and movements in adults with tic disorders. Clin. Neurophysiol. July 2023; 151: 143–150. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTsetsos F, Topaloudi A, Jain P, et al.: Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome. Biol. Psychiatry. 2023. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTygesen MLB, Maigaard K, Hagstrøm J, et al.: Fine Motor Skills in Children with Tourette Syndrome and their Unaffected First-degree Siblings. Scand J. Child Adolesc. Psychiatr. Psychol. 2023; 11: 60–68. PubMed Abstract | Publisher Full Text\n\nvan de Griendt JMTM , van den Berg NME , Verdellen CWJ, et al.: Working Mechanisms of Exposure and Response Prevention in the Treatment of Tourette Syndrome and Tic Disorders Revisited: No Evidence for within-Session Habituation to Premonitory Urges. J. Clin. Med. 2023; 12: 12. Publisher Full Text\n\nVerdellen CW, van de Griendt J , Kriens S, et al.: Tics - Therapist Manual. Boom Publishers; 2011.\n\nVicario CM, Maugeri N, Lucifora C, et al.: Evidence for a dissociation between moral reasoning and moral decision-making in Tourette syndrome. J. Neuropsychol. 2023. PubMed Abstract | Publisher Full Text\n\nVilela-Filho O, Souza JT, Ragazzo PC, et al.: Bilateral Globus Pallidus Externus Deep Brain Stimulation for the Treatment of Refractory Tourette Syndrome: An Open Clinical Trial. Neuromodulation Technol. Neural Interface. June 2023. PubMed Abstract | Publisher Full Text\n\nWang S, Wang B, Drury V, et al.: Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD. Nat. Commun. 2023; 14: 8077. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWehmeyer L, Schüller CB, Gruendler TOJ, et al.: Electrophysiological Correlates of Proactive Control and Binding Processes during Task Switching in Tourette Syndrome. eNeuro. April 2023; 10(4): ENEURO.0279–ENEU22.2023. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWeiblen R, Robert C, Petereit P, et al.: Neural, physiological and behavioural correlates of empathy for pain in Tourette syndrome. Brain Commun. 2023; 5(4). PubMed Abstract | Publisher Full Text | Free Full Text\n\nWellen BCM, Bootes KR, Braley EI, et al.: Caregiver Perspectives on the Health Care System for Tic Disorders: Utilization and Barriers. J. Dev. Behav. Pediatr. 2023; 44: e581–e589. PubMed Abstract | Publisher Full Text\n\nWendiggensen P, Paulus T, Bluschke A, et al.: Theta Activity Dynamics during Embedded Response Plan Processing in Tourette Syndrome. Biomedicines. January 2023; 11(2). PubMed Abstract | Publisher Full Text | Free Full Text\n\nWillford S, Deeb W: Scoping Review of Multidisciplinary Care in Tourette Syndrome. Mov. Disord. Clin. Pract. 2023; 10: 868–877. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWoods DW, Piacentini JC, Chang SW, et al.: Managing Tourette syndrome: a behavioral intervention for children and adults therapist guide. New York: Oxford University Press; 2008.\n\nXin X, Feng Y, Lou Y, et al.: Abnormal dynamics of brain functional networks in children with Tourette syndrome. J. Psychiatr. Res. March 2023; 159: 249–257. PubMed Abstract | Publisher Full Text\n\nYang Y, Yang H, Yu C, et al.: Alterations in the topological organization of the default-mode network in Tourette syndrome. BMC Neurol. 2023; 23(1): 390. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYu D, Sul JH, Tsetsos F, et al.: Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies. Am. J. Psychiatry. 2019; 176: 217–227. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZouki J-J, Ellis EG, Morrison-Ham J, et al.: Mapping a network for tics in Tourette syndrome using causal lesions and structural alterations. Brain Commun. April 2023; 5(3): fcad105. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "298065",
"date": "05 Jul 2024",
"name": "Roger L Albin",
"expertise": [
"Reviewer Expertise Movement Disorders"
],
"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 thorough, thoughtful, and easily readable summary of the last year’s contributions to the burgeoning literature on Tourette syndrome and related disorders. There is a generally nice balance between description and critical assessments. I have only a few minor comments. The Du et al. study (Annals of Neurology) was based on the concept that there is a substantial developmental deficit of striatal cholinergic interneurons. There is no in vivo evidence for this concept and PET imaging data to the contrary. In addition, the behavioral methods used in this study have an uncertain relationship to tic behaviors. The relevance of this work is unclear. I think the Highlights within Highlights section is both accurate and useful. I’d ask the authors to consider a few points related to their “Scrying the future…” section. As a minor point, this section mentions neurosteroids, which I don’t think are mentioned anywhere else. Why bring this up at the very end? I’m compelled to respond to the authors’ comments that the typical age of tic onset and male predominance are “mysterious.” I certainly agree these are very relevant phenomena but there is an existing conceptual framework that might be a point of departure for investigations [Refer ref 1].How would organoids contribute to studying “pathophysiology?” A standard definition of the latter is “the disordered physiological processes associated with disease or injury.” As the authors relate nicely, there is quite a bit of neuroimaging and ephys data on altered brain circuit-network dynamics driving the clinical features of TS. How would a highly reduced preparation like an organoid reproduce these kinds of phenomena? Indeed, if a behavior is the defining feature of a disorder, how can you know what is relevant in an organoid?\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Yes\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": "12160",
"date": "09 Aug 2024",
"name": "Andreas Hartmann",
"role": "Author Response",
"response": "Response: We thank Dr. Albin for his comments. Parenthetically, we would identify this review as an example of the potential benefits of open review: here we have a world expert providing thoughtful and critical feedback that proves equal or superior in utility to those we have received over the years from traditional unsigned reviews. Dr. Albin raises four primary concerns. We summarize them below, each followed by our response. The Du et al. study (Annals of Neurology) was based on the concept that there is a substantial developmental deficit of striatal cholinergic interneurons. There is no in vivo evidence for this concept and PET imaging data to the contrary. In addition, the behavioral methods used in this study have an uncertain relationship to tic behaviors. The relevance of this work is unclear. Response: The work discussed in the “Animal models” section was motivated by reduced striatal cholinergic interneurons in autopsy samples from five TS patients, a finding not supported by the only in vivo human study, a quantitative PET study of 12 young adults with TS and 10 tic-free comparison adults. We have added this concern to the text. I think the Highlights within Highlights section is both accurate and useful. I’d ask the authors to consider a few points related to their “Scrying the future…” section. As a minor point, this section mentions neurosteroids, which I don’t think are mentioned anywhere else. Why bring this up at the very end? Response: Articles about neurosteroids in TS were inadvertently omitted from the review section. We have added two sections to the text to correct this omission, one in Pathophysiology / Animal models and one in Treatment / Pharmacological studies. I’m compelled to respond to the authors’ comments that the typical age of tic onset and male predominance are “mysterious.” I certainly agree these are very relevant phenomena but there is an existing conceptual framework that might be a point of departure for investigations [Refer ref 1]. Response: We were very impressed by Dr. Albin’s unifying theory of TS as a disorder of the brain networks that underlie social decision-making (Albin 2018, 2019). Somehow we missed the important comments there about how that construct can explain the age of tic onset and the high male:female sex ratio. Thank you for directing our attention to these comments ! We have removed those two from the list of interesting mysteries. How would organoids contribute to studying “pathophysiology?” A standard definition of the latter is “the disordered physiological processes associated with disease or injury.” As the authors relate nicely, there is quite a bit of neuroimaging and ephys data on altered brain circuit-network dynamics driving the clinical features of TS. How would a highly reduced preparation like an organoid reproduce these kinds of phenomena? Indeed, if a behavior is the defining feature of a disorder, how can you know what is relevant in an organoid? Response: Dr. Albin correctly points out that a blob of brain cells in a dish cannot produce tics, and cannot recapitulate the whole-brain findings from EEG or neuroimaging studies that in any case are more relevant in living humans. Nevertheless, we believe it is appropriate to hypothesize that human brain organoids derived from pluripotent stem cells (hBOs) may at some point reveal useful information relevant to pathophysiology of TS. Specifically, hBOs can be created from samples of people with and without TS. The two groups of organoids (TS+ / TS−) can be compared in several ways, such as to identify differences in specific neuronal types, neurochemicals or firing patterns. Such differences can direct attention to similar regions of the human brain in autopsy or in vivo studies. Novel treatments can be tested to see if they correct any such differences. Specific genes identified as potentially causative in human studies can be examined in hBOs to identify developmental effects caused by manipulating those genes, for instance with optogenetic or CRISPR methods. All of these possibilities are speculative at this moment, and may or may not prove plausible (or ethical, if hBO complexity progresses substantially beyond its current level). However, similar studies have been conducted successfully in idiopathic autistic disorder (Mariani et al. 2015) and other more dramatic neurodevelopmental conditions (Chiaradia and Lancaster 2020, Wang et al. 2023). There is no room in the article to discuss this issue adequately, but that seems appropriate for a speculative “what may be in the future” section of a review. We have left the speculation in place in the article text. References cited in the response to reviewers Albin RL. Tourette syndrome: a disorder of the social decision-making network. Brain. 2018 Feb 1;141(2):332-347. PubMed PMID: 29053770. Pubmed Central PMCID: PMC5837580. doi 10.1093/brain/awx204. Albin RL. Tourette syndrome as a disorder of the social decision making network. Front Psychiatry. 2019;10:742. PubMed PMID: 31649568. Pubmed Central PMCID: PMC6792345. Epub 20191008. doi 10.3389/fpsyt.2019.00742. Chiaradia I, Lancaster MA. Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo. Nat Neurosci. 2020 Dec;23(12):1496-1508. PubMed PMID: 33139941. Epub 20201102. doi 10.1038/s41593-020-00730-3. Mariani J, Coppola G, Zhang P, et al. FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders. Cell. 2015 Jul 16;162(2):375-390. PubMed PMID: 26186191. Pubmed Central PMCID: PMC4519016. doi 10.1016/j.cell.2015.06.034. Wang L, Owusu-Hammond C, Sievert D, et al. Stem Cell-Based Organoid Models of Neurodevelopmental Disorders. Biol Psychiatry. 2023 Apr 1;93(7):622-631. PubMed PMID: 36759260. Pubmed Central PMCID: PMC10022535. Epub 20230124. doi 10.1016/j.biopsych.2023.01.012."
}
]
},
{
"id": "298068",
"date": "22 Jul 2024",
"name": "Lorena Fernández de la Cruz",
"expertise": [
"Reviewer Expertise obsessive-compulsive and related disorders",
"tic disorders",
"cognitive behavior 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\nThank you for the opportunity to review another informative instance (the 10th!) of the yearly TS research highlights. I commend the authors for their commitment and for the work itself, which provides a helpful update to both those in the field of TS and curious minds outside of it.\nThis is a narrative review restricted to one database (PubMed/MEDLINE), which makes it non-exhaustive but thorough enough for the purpose of the piece. With this in mind, the review follows appropriate methods and critically describes the most relevant published papers in the field of TS/tic disorders, organized by area of knowledge. I do not have major comments but would like to mention some minor points.\nWhen describing the work by Baizabal-Carvallo and Jankovik (2023), I believe that the reader would benefit from a brief explanation of what the authors mean by “blocking phenomenon”. This is defined in the abstract of the original study (i.e., blocking phenomena are characterized by arrests in motor activity causing interruptions in movements or speech).\nThe summary of the work by Mataix-Cols et al (2024) includes a typo which is important for the interpretation of the results. The sentence “20% of children with tic disorder received a chronic tic disorder diagnosis in childhood” should instead read “20% of children with tic disorder received a chronic tic disorder diagnosis in adulthood.”\nWhen discussing the study by Martino et al (2023) on a large cohort of individuals with functional tic-like behaviors (FTLB), the authors say: “Again, a high number (60%) reported exposure to social media.” Please clarify that this refers specifically to exposure to tic-related social media content, as mentioned in the original article.\nWhile reading the piece, I wondered if the focus on FTLB (with one section under “Phenomenology and natural history” and a section under “Treatment”) was not excessive, particularly considering that the authors mention that this review article is becoming more voluminous by the year. The studies on the differential diagnosis between tic disorders and FTLB and their comorbidity are in my opinion very fitting and of help from the clinical point of view. However, other articles focused on samples of FTLB alone, as interesting as they are, may be out of scope (maybe with some exceptions).\nSome acronyms are used but never defined (e.g., ADHD, PUTS, HD). These are most likely well known by the readership but please define for sense of completion the first time that they are mentioned.\nThere are several typos throughout the article. It would be good if the authors could read through and correct them. A few that I caught are listed below:\nDescription of Larsh et al, 2023a: please write “higher in adolescent girls than in boys” instead of “then in boys”. Larsh et al, 2024: “sex differences in tic severity by retrospectively reviewing Yale Global Tic Severity Scale (YGTSS)”. Something seems to be missing in this clause. Maybe rephrase to “sex differences in tic severity were explored by retrospectively reviewing Yale Global Tic Severity Scale (YGTSS)”? Larsh et al, 2024: “but during the pandemic where girls had more severe tics than boys”. Remove the “where”. Lewin et al, 2023: “only a subset of questions” instead of “only subset of questions” / “both versions of the scale” instead of “both version of the scale”. The acronym FTLB is first used when describing the study by Jack et al. (2023) but it is not defined until the following paragraph/section. Nilles et al., 2023: “83 youth” is mentioned twice. Colreavy et al, 2023: “sleep patterns were more impacted” instead of “sleep patterns was more impacted”.\nIn sum, I think the article represents a good addition to the TS literature and I recommend its indexing.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Yes\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? Yes",
"responses": [
{
"c_id": "12161",
"date": "09 Aug 2024",
"name": "Andreas Hartmann",
"role": "Author Response",
"response": "Response: We thank Dr Fernández de la Cruz for her thorough review of our yearly review, again ! It is very much appreciated. Below the answers to her queries. When describing the work by Baizabal-Carvallo and Jankovik (2023), I believe that the reader would benefit from a brief explanation of what the authors mean by “blocking phenomenon”. This is defined in the abstract of the original study (i.e., blocking phenomena are characterized by arrests in motor activity causing interruptions in movements or speech). Response: Thank you for this suggestion, we have modified the manuscript accordingly. The summary of the work by Mataix-Cols et al (2024) includes a typo which is important for the interpretation of the results. The sentence “20% of children with tic disorder received a chronic tic disorder diagnosis in childhood” should instead read “20% of children with tic disorder received a chronic tic disorder diagnosis in adulthood.” Response: Thank you for your vigilance, we have modified the manuscript accordingly. When discussing the study by Martino et al (2023) on a large cohort of individuals with functional tic-like behaviors (FTLB), the authors say: “Again, a high number (60%) reported exposure to social media.” Please clarify that this refers specifically to exposure to tic-related social media content, as mentioned in the original article. Response: Thank you, for this suggestion, we have modified the manuscript accordingly. While reading the piece, I wondered if the focus on FTLB (with one section under “Phenomenology and natural history” and a section under “Treatment”) was not excessive, particularly considering that the authors mention that this review article is becoming more voluminous by the year. The studies on the differential diagnosis between tic disorders and FTLB and their comorbidity are in my opinion very fitting and of help from the clinical point of view. However, other articles focused on samples of FTLB alone, as interesting as they are, may be out of scope (maybe with some exceptions). Response: We understand the concern but still in 2023 (and 2024 for that matter), FTLB remain what one could call a “big deal” and, to some extent, a game changer in our field. One current example – that will be incorporated in the 2024 annual highlight paper – is the impact FTLB have and will have on our classification of neurodevelopmental tics, as Dr. Fernández de la Cruz points out (cf. Sarchioto et al., Mov Disord 2024, Jun 18. doi: 10.1002/mds.29868. Epub ahead of print. PMID 38894500.). However, since TS specialists are now also increasingly caring for patients with FTLB on a regular and an extended basis, we believe it is justified to keep articles dedicated solely to FTLB in our yearly review. In a way, even though it is a different entity, FTLB is also an extension of our primary line of work. Some acronyms are used but never defined (e.g., ADHD, PUTS, HD). These are most likely well known by the readership but please define for sense of completion the first time that they are mentioned. Response: Thank you for your vigilance, we have modified the manuscript accordingly. There are several typos throughout the article. It would be good if the authors could read through and correct them. A few that I caught are listed below: Description of Larsh et al, 2023a: please write “higher in adolescent girls than in boys” instead of “then in boys”. Larsh et al, 2024: “sex differences in tic severity by retrospectively reviewing Yale Global Tic Severity Scale (YGTSS)”. Something seems to be missing in this clause. Maybe rephrase to “sex differences in tic severity were explored by retrospectively reviewing Yale Global Tic Severity Scale (YGTSS)”? Larsh et al, 2024: “but during the pandemic where girls had more severe tics than boys”. Remove the “where”. Lewin et al, 2023: “only a subset of questions” instead of “only subset of questions” / “both versions of the scale” instead of “both version of the scale”. The acronym FTLB is first used when describing the study by Jack et al. (2023) but it is not defined until the following paragraph/section. Nilles et al., 2023: “83 youth” is mentioned twice. Colreavy et al, 2023: “sleep patterns were more impacted” instead of “sleep patterns was more impacted”. Response: Thank you for your vigilance, we have modified the manuscript accordingly."
}
]
}
] | 1
|
https://f1000research.com/articles/13-677
|
https://f1000research.com/articles/13-807/v1
|
17 Jul 24
|
{
"type": "Research Article",
"title": "A study of association between early menarche and anxiety in undergraduate students",
"authors": [
"Poorva Bakshi",
"Sharanya B. Shetty",
"Abira Sharma",
"Vasudha K G",
"Keshava Pai",
"Radhika K",
"Priyanka Renita D'Souza",
"Reshma N S",
"Poorva Bakshi",
"Abira Sharma",
"Vasudha K G",
"Keshava Pai",
"Radhika K",
"Priyanka Renita D'Souza",
"Reshma N S"
],
"abstract": "Background Anxiety has been reported to be one of the most common epidemics in recent years. The present study focused on understanding the association between early menarche and the prevalence of anxiety and anxiety symptoms among adult undergraduate students.\n\nMethods This was an observational, case-control study. The sample included 146 young female adults aged more than or equal to 18 years pursuing the Bachelor of Medicine and Bachelor of Surgery (MBBS) and Bachelor of Dental Sciences (BDS). Using an online questionnaire, participants were asked to recall and enter the age at which they attained menarche. We used the Generalized Anxiety Disorder 7- Item Questionnaire (GAD-7) to measure the severity of their present anxiety symptoms.\n\nResults The results showed a significant increase in anxiety symptoms in participants who had early menarche compared to those who did not have early menarche. The mean score on the GAD-7 Questionnaire for the cases was 9.93 and the control group was 6.89. The GAD-7 scores among the cases group were significantly higher in the GAD-7 scores than in the control group.\n\nConclusions This study concluded that early menarche is associated with higher anxiety levels in young adults.",
"keywords": [
"early menarche",
"anxiety",
"young adults",
"mental health in young",
"early puberty"
],
"content": "Introduction\n\nAnxiety is the world’s most common mental health disorder, affecting 301 million people worldwide in 2019. It has also been reported that women are affected more by anxiety disorders than men, and their symptoms surge during childhood or adolescence. It is also stated that approximately one in four people with anxiety disorders receive treatment, which reflects that only a minority of the population affected is receiving adequate healthcare.1\n\nThe United Nations Sustainable Development Goal (UN SDG 3) focuses on good health, which includes mental health, whereas the UN SDG 5 focuses on gender equality. An intersection between these two goals is the mental health of women, which has long been neglected, leading to a gap in the quality of the healthcare provided to men and women. To bridge this gap, it is imperative to study the factors affecting mental health specific to women.2\n\nIn recent decades, there has been a trend of decreasing mean age at menarche in India.3 Early menarche is defined as menarche at or below 12 years of age.4 Eating habits and a higher body mass index have been implicated as risk factors for early menarche.4\n\nPuberty is a formative period during which several hormonal, reproductive, and social changes occur. The psychological effects of early puberty may not be limited to adolescence but may also affect mental health during adulthood.5\n\nA study conducted on secondary school female students aged 12 to 17 years reflected the association between menarche and the prevalence of anxiety and depression comorbidities.6\n\nStudies have evaluated the difference in the effect of pubertal timing between males and females. While early puberty tends to have a positive impact in males, it is linked to increased symptoms of depression among females.7\n\nSocial stress after puberty and changes in peer, sexual and family connections have been linked to emotional issues in early adolescence.7,8\n\nThe long-term developmental consequences of pubertal timing reported that girls who mature early continue to have a higher risk of anxiety throughout adolescence and early adulthood.9,10 Because early menarche leads to an abrupt transition, it leaves little time for emotional preparation. Girls who mature early may experience anxiety and related symptoms.11\n\nSeveral studies have reported an association between early menarche and psychosocial pathologies in adolescents. Early menarche is associated with increased substance abuse, elevated depression, and suicidal behaviors in adolescent girls.12,13\n\nThe effect of early menarche on mental health in adulthood remains controversial. Some studies have shown that early menarche is associated with depressive symptoms and antisocial behavior in adults,14 while other studies have shown that there is no association between early menarche and symptoms of depression.15 An association has been found between anxiety disorders in adult women and early perceived pubertal timing.16\n\nThe fluctuation of estrogen levels during the reproductive lifespan of women has been frequently studied and linked to various psychiatric disorders.17 However, the role of estrogen in anxiety has not been determined. Increased anxiety levels are observed during menarche, which is the time at which estrogen levels become elevated.6 In contrast, animal experiments have shown that acute and chronic estrogen administration have anxiolytic effects.18 Estrogen acts through three estrogen receptor (ER) subtypes, which have different effects on anxiety. Estrogen Receptor alpha (ER alpha) has anxiogenic effects, estrogen receptor beta (ER beta) has anxiolytic effects, and G protein-coupled estrogen receptor (GPR30) has both anxiolytic and anxiogenic effects.19\n\nAccording to studies that have been conducted in this area, there is an established correlation between early puberty and mental illness in the adolescent population.9–13 However, the association between early menarche and psychiatric illnesses in adulthood is not well understood.14–16 We aimed to understand whether there is an association between early puberty and anxiety symptoms in women aged more than or equal to 18 years. Age at menarche was chosen for this study because it is an objective measurement. We selected undergraduate students pursuing Bachelor of Medicine and Bachelor of Surgery (MBBS) and Bachelor of Dental Sciences (BDS), as it was presumed that academic stressors among these students may be similar, thus reducing an important confounding factor.\n\nThis research aimed to understand the relation between early menarche and anxiety during adulthood.\n\n\nMethods\n\nStudy setting: The study was conducted in Kasturba Medical College and Hospital, Mangalore.\n\nStudy design: This study was conducted as an analytical observational case control study.\n\nStudy participants: Female undergraduate students studying in Kasturba Medical College, Mangalore and Manipal College of Dental Sciences, Mangalore.\n\nCases:\n\n1. Age more than or equal to 18 years\n\n2. Age at menarche less than or equal to 12 years\n\n3. Undergraduate students willing to consent for the study\n\nControls:\n\n1. Age more than or equal to 18 years\n\n2. Age at menarche greater than 12 years\n\n3. Undergraduate students willing to consent for the study\n\nCases and controls\n\n1. Age less than 18 years\n\n3. Participants unwilling to give consent\n\n4. Incomplete filling of questionnaire\n\n5. Participants who could not recall age at menarche\n\nStudy duration: The study was conducted over 7 months, from June 2023 to December 2023.\n\nThe estimated sample size for the study was 76 for each group, with 5% significance level and 80% power. The total sample size estimated for the study was 152 participants.\n\nn = 75.8\n\nZ1α = 1.96 is a standard normal value for 95% confidence interval\n\nZ1β = 0.84 is a standard normal value at 80% power\n\nσ = standard deviation = 31.1\n\nd = clinically significant difference = 10\n\nSampling method: Convenient sampling method\n\nThe study questionnaire was uploaded and shared online on Google Forms. A link to the electronic questionnaire was distributed in the college campus via e-mail, WhatsApp, and Online class groups. The questionnaire had an introductory page describing the background and aims of the study, ethical information for the participants, and informed consent. Once the participant clicked on the ‘I agree’ button, they were directed to the next sections of the questionnaire. Participants were able to leave the questionnaire at any stage before the submission process. If they left in between, their responses were not saved. Responses were saved only by clicking on the ‘submit’ button. By completing the questionnaire, participants acknowledged their voluntary consent to be included in the study.\n\nThe questionnaire had the following sections.\n\nSection A: General participant information\n\nThis contains the sociodemographic information of the participants, including age, place of residence, and so on.\n\nSection B: Age at menarche and menstrual history\n\nThis consists of age at menarche based on recall, history of dysmenorrhea, any known thyroid disorder, and any known gynecological disorder.\n\nSection C: Generalized Anxiety Disorder 7-Item (GAD-7) Questionnaire20\n\nThe GAD-7 Scale is a seven-point scale commonly used to assess anxiety in clinical as well as educational settings. Participants marked their answers on a scale of not at all, several days, more than half the days, and nearly every day. The GAD-7 score is calculated by assigning scores of 0 to “not at all,” 1 to “several days,” 2 to “more than half the days,” 3 to “nearly every day.” Thus, the scores range from 0 to 21. The interpretation of the score would be 0–4, minimal anxiety; 5–9, mild anxiety; 10–14, moderate anxiety; and 15–21, severe anxiety.\n\nSection D: Anxiety symptoms\n\nIn this section, further questions were asked regarding the duration and treatment of anxiety symptoms experienced by the participants.\n\nBiological materials required: none.\n\nStatistical analysis was performed using IBM SPSS Statistics for Windows version 29 (IBM Corp., Armonk, N.Y., USA).21 A copyright licence was obtained by the institution.\n\nStatistical significance was set at p value<0.05. Descriptive statistics such as mean, proportions, and standard deviation were used to express the results. The t-test was used for continuous variables, and the chi-square test was used for categorical variables.\n\n\nResults\n\nThe present study comprised a total of 146 participants after excluding participants who did not adhere to our inclusion and exclusion criteria.\n\nThe age of the participants in our study ranged from 18 to 25 years. The mean age was 20.54±1.7 years.\n\nThe age at menarche of the participants ranged from 10 to 16 years. The mean age at menarche of our participants was 12.48±1.17 years.\n\nThe participants were grouped into case and control groups based on age at menarche. The participants with age at menarche less than or equal to 12 years were the cases and the control group consisted of participants with age at menarche greater than 12 years. We had 74 participants in the cases group and 72 participants in the control group.\n\nThe mean score for the cases on the GAD-7 questionnaire was 9.93 (Standard deviation=6.05). The mean score for the controls on the GAD-7 questionnaire was 6.89 (Standard deviation=5.24). An independent t-test was performed, and it was found that the GAD-7 scores of the cases were significantly higher than the GAD-7 scores of the controls with a (t(144)=3.26, p<0.05). Thus, the difference in the GAD-7 scores between the cases and controls was found to be significant.\n\nAmong the cases, 20.3% had minimal anxiety, 32.4% had mild anxiety, 21.6% had moderate anxiety, and 25.7% had severe anxiety. Among the controls 38.9%, 30.6%, 25.0% and 5.6% had minimal, mild, moderate, and severe anxiety, respectively.\n\nIn the cases, 66 of 74 participants entered their age at the onset of anxiety symptoms. Among the controls, 56 out of 72 participants entered their age at the onset of anxiety symptoms. These findings are summarized in Table 1.\n\nAmong the cases out of 74 participants, 65 responded to the question regarding the duration of their anxiety symptoms. Among the controls, 55 out of 72 participants responded to questions regarding the duration of their anxiety symptoms. The findings regarding the duration of the anxiety symptoms are summarized in Table 2.\n\nOf the 146 participants in the present study, 122 answered the question regarding whether they had received treatment for their anxiety symptoms. 20.5% had received treatment for their symptoms. Thirty participants reported details of the treatment they received. Of these, 12 participants (40%) received pharmacological treatment, 16 (53.3%) received psychological treatment, 1 (3.3%) received both psychiatric and Ayurvedic treatment, and 1 (3.3%) received crystal stone treatment.\n\nAmong 146 study participants, 26 participants reported to have known gynecological condition, among them 23 reported to have polycystic ovarian syndrome. Six participants reported to have known thyroid condition.\n\n\nDiscussion\n\nThe present study focused on the association between early menarche and anxiety during adulthood. This was an analytical observational case-control study of female undergraduate students aged more than or equal to 18 years.\n\nThe mean age at menarche in our study was 12.48±1.17 years. Their ages ranged from 10 to 16 years. The mean age at menarche was found to be lower than the mean age at menarche in India calculated as of 2005 which was 13.76 years.3 More recently, studies have shown a decline in the mean age at menarche between mothers and daughters.22 A study conducted among North Indian girls in 2023 found the mean age of menarche to be 13.13±1.23 years.23 The mean age at menarche in our study was found to be even lower than these.\n\nThe present study found that anxiety symptoms were significantly higher in participants with an early age at menarche. These findings further support those of numerous studies, which show that early puberty and menarche are associated with greater rates of morbidity of anxiety and other psychiatric illnesses than relatively late menarche.9–13 Other studies have found that females who mature early are more likely to experience symptoms of psychiatric illnesses, including anxiety, throughout adolescence and during the early stages of adulthood.9,10\n\nEmotional problems in early adolescence have been connected to social stress following puberty and modifications in peer, sexual, and family relationships.7,8 It is evident that in females, menarche becomes a sudden transition that provides little time for emotional preparation and can cause anxiety and related symptoms.11 During the perimenarcheal phase, participants described feeling puzzled, worried, and ambivalent, but eventually acclimated to these changes.11\n\nThese findings can also be explained by estrogen variations in women. Several studies have attempted to explain the effects of estrogen on mental health.24–26 Menarche, the period when estrogen levels rise, is associated with higher anxiety levels.17 However, the anxiolytic effects of both acute and chronic estrogen treatments have been demonstrated in animal models.18 Estrogen has distinct effects on each subtype of the receptor through a complex interaction.19 This study followed an objective metric, age at menarche, to investigate the relationship between anxiety during adulthood and early puberty.\n\nAmong the cases, 20.3% had minimal anxiety, 32.4% had mild anxiety, 21.6% had moderate anxiety, and 25.7% had severe anxiety. Among the controls 38.9%, 30.6%, 25.0% and 5.6% had minimal, mild, moderate, and severe anxiety, respectively. A larger percentage of the women in the case group experienced severe anxiety. However, a greater percentage of the women in the control group experienced minimal anxiety.\n\nIn our study, we found that 59.1% of cases and 67.9% of controls first experienced anxiety symptoms after 18 years of age. In contrast, 27.3% of the cases and 25% of the controls first experienced anxiety symptoms between the ages of 14-17 years of age. A previous study found that the mean age of onset of generalized anxiety disorder was between 21.1 and 34.9 years.27 However, this was only partially reflected in our study, probably because the mean age of our participants was 20.54±1.7 years.\n\nAccording to our study, the duration of anxiety symptoms was less than 6 months in 30.8% of cases and 32.7% of controls. The duration of anxiety symptoms was between 6 and 12 months in 16.9% of cases and 29.1% of controls. The duration of anxiety symptoms was greater than one year in 52.3% of the cases and 38.2% of the controls. A study found the mean duration of anxiety symptoms to be 15.2 months,28 which was in line with our findings.\n\nOf the 122 participants who answered the question, 20.5% received treatment for their symptoms. A study by the World Health Organization on the treatment gap in anxiety disorders also showed that only 27.6% of the respondents who had anxiety disorder had received treatment of any form, and only 9.8% had possibly received adequate treatment. It is evident that there is a need to diagnose anxiety disorders and improve the treatment quality.29\n\nOf the participants who reported receiving treatment, 12 participants (40%) received pharmacological treatment, 16 (53.3%) received psychological treatment, 1 (3.3%) received both psychiatric and Ayurvedic treatment, and 1 (3.3%) received crystal stone treatment. In general, the first-line treatment for generalized anxiety is cognitive behavioral therapy (CBT) and pharmacotherapy (SSRIs, SNRIs). Others include benzodiazepines for acute cases, metacognitive therapy, mindfulness techniques, physical activities, and Acceptance and Commitment Therapy).30 Most participants in our study relied on allopathic treatments, whereas a minority resorted to alternative treatment methods.\n\nThis study sheds light on anxiety symptoms associated with early menarche. Further implications of this study include understanding other psychiatric comorbidities associated with early menarche and puberty.\n\nOther stressors, genetic predisposition, lifestyle, environmental causes, and medical history, which may be confounding variables, were not considered in this study. A larger sample size should be considered, and a population-based study should be conducted to increase the likelihood of generalizability of the entire population. Future studies with a longitudinal cohort design are warranted.\n\n\nConclusion\n\nThis study indicated that individuals with early menarche had significantly higher anxiety symptoms during adulthood. Healthcare providers need to be sensitized to early pubertal timing in young adults with anxiety. It is a matter of concern that early menarche could have a serious negative impact on developing adolescents and young adults.\n\nThe data analysis in this study was not pre-registered.\n\nThe protocol was approved by the Institutional Ethics Committee Kasturba Medical College,\n\nMangalore (Reg. No. ECR/541/Inst/KA/2014/RR-20) before the commencement of the study, and Ethical Approval was obtained. Protocol number of the study used was IEC KMC MLR 05/2023/212. The date of approval was 17/05/2023.\n\n\nConsent\n\nThe introductory form of the online survey had information about the background, aim of the study and the consent form. Once the participant clicked on the ‘I agree’ button, this was considered consent for participating in the study and the participant was taken to the rest of the questionnaire. The participants had the right to withdraw from the study at any time.",
"appendix": "Data availability\n\nOpen Science Framework: A study of association between early menarche and anxiety in undergraduate students. https://doi.org/10.17605/OSF.IO/RA2V6 31\n\nThis project contains the following underlying data:\n\n• Association between Early Menarche and Anxiety in Undergraduate Students.pdf (Questionnaire which was circulated via google forms).\n\n• Consent Form.docx\n\n• Complete Participant Responses. xlsx (record of all responses collected)\n\n• STROBE Checklist. Docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nThis study was based on the STROBE (The Strengthening the Reporting of Observational studies in Epidemiology) guidelines. 32\n\n\nAcknowledgements\n\nThe undergraduate students of Kasturba Medical College Mangaluru and Manipal College of Dental Sciences Mangaluru.\n\n\nReferences\n\nWorld Health Organization: Anxiety disorders. World Health Organization; 2023. Reference SourceReference Source\n\nUnited Nations: Sustainable Development Goals. [Accessed 2023-11-12]. Reference Source\n\nPathak PK, Tripathi N, Subramanian SV: Secular trends in menarcheal age in India-evidence from the Indian Human Development Survey. PLoS One. 2014; 9(11): e111027. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee HS: Why should we be concerned about early menarche? Clin. Exp. Pediatr. 2021; 64(1): 26–27. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMendle J, Ryan RM, McKone KMP: Early menarche and internalizing and externalizing in adulthood: Explaining the persistence of effects. J. Adolesc. Health. 2019 Nov; 65(5): 599–606. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPatton GC, Hibbert ME, Carlin J, et al.: Menarche and the onset of depression and anxiety in Victoria, Australia. J. Epidemiol. Community Health. 1996 Dec 1; 50(6): 661–666. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAngold A: Puberty onset of gender differences in rates of depression: a developmental, epidemiologic and neuroendocrine perspective. J. Affect. Disord. 1993 Nov; 29(2-3): 145–158. PubMed Abstract | Publisher Full Text\n\nPeterson A, Compas B, Brooks-Gunn J, et al.: Depression in adolescence. Am. Psychol. 1993; 48: 155–168. Publisher Full Text\n\nGraber JA, Seeley JR, Brooks-Gunn J, et al.: Is Pubertal Timing Associated With Psychopathology in Young Adulthood? J. Am. Acad. Child Adolesc. Psychiatry. 2004 Jun; 43(6): 718–726. PubMed Abstract | Publisher Full Text\n\nZehr JL, Culbert KM, Sisk CL, et al.: Early puberty is associated with disordered eating and anxiety in young adults. Front. Neuroendocrinol. 2006 May; 27(1): 139–140. Publisher Full Text\n\nRuble DN, Brooks-Gunn J: The Experience of Menarche. Child Dev. 1982 Dec; 53(6): 1557. Publisher Full Text\n\nStice E, Presnell K, Bearman SK: Relation of early menarche to depression, eating disorders, substance abuse, and comorbid psychopathology among adolescent girls. Dev. Psychol. 2001; 37(5): 608–619. PubMed Abstract | Publisher Full Text\n\nKim SR, Lee S, Chung JH: Association between early menarche and suicidal behaviors in Korean girl adolescents. Medicine. 2021; 100(38): e27301. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShen Y, Varma DS, Zheng Y, et al.: Age at menarche and depression: Results from the NHANES 2005–2016. PeerJ. 2019; 7: e7150. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOpoliner A, Carwile JL, Blacker D, et al.: Early and late menarche and risk of depressive symptoms in young adulthood. Arch. Womens Ment. Health. 2014; 17(6): 511–518. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWeingarden H, Renshaw KD: Early and late perceived pubertal timing as risk factors for anxiety disorders in adult women. J. Psychiatr. Res. 2012; 46(11): 1524–1529. PubMed Abstract | Publisher Full Text\n\nGeorgiou P, Zanos P, Jenne CE, et al.: Sex-specific involvement of estrogen receptors in behavioral responses to stress and Psychomotor Activation. Front. Psych. 2019 Feb 26; 10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKalandakanond-Thongsong S, Daendee S, Srikiatkhachorn A: Effect of the acute and chronic estrogen on anxiety in the elevated T-maze. Physiol. Behav. 2012; 105(2): 357–363. PubMed Abstract | Publisher Full Text\n\nBorrow AP, Handa RJ: Estrogen receptors modulation of anxiety-like behavior. Anxiety. 2017; 27–52. PubMed Abstract | Publisher Full Text | Free Full Text\n\nToussaint A, Hüsing P, Gumz A, et al.: Sensitivity to change and minimal clinically important difference of the 7-item generalized anxiety disorder questionnaire (GAD-7). J. Affect. Disord. 2020; 265: 395–401. PubMed Abstract | Publisher Full Text\n\nIBM Corp: IBM SPSS Statistics for Windows, Version 29.0. Armonk, NY: IBM Corp;\n\nRamraj B, Subramanian VM, G V.: Study on age of menarche between generations and the factors associated with it. Clin. Epidemiol. Glob. Health. 2021 Jul; 11: 100758. Publisher Full Text\n\nBajpai A, Bansal U, Rathoria R, et al.: A prospective study of the age at menarche in North Indian Girls, its association with the tanner stage, and the secular trend. Cureus. 2023 Sept 16; 15: e45383. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMehta D, Rex-Haffner M, Søndergaard HB, et al.: Evidence for oestrogen sensitivity in perinatal depression: Pharmacological sex hormone manipulation study. Br. J. Psychiatry. 2018 Nov 20; 215(3): 519–527. PubMed Abstract | Publisher Full Text\n\nLei R, Sun Y, Liao J, et al.: Sex hormone levels in females of different ages suffering from depression. BMC Womens Health. 2021 May 22; 21(1): 215. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSundermann EE, Maki PM, Bishop JR: A review of estrogen receptor α gene (ESR1) polymorphisms, mood, and cognition. Menopause. 2010 Jul; 17(4): 874–886. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLijster JM, Dierckx B, Utens EMWJ, et al.: The age of onset of anxiety disorders. Can. J. Psychiatry. 2016 Mar 24; 62(4): 237–246. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHave M, Tuithof M, Dorsselaer S, et al.: Duration of anxiety disorder and its associated risk indicators: Results of a longitudinal study of the general population. Depress. Anxiety. 2020 Oct 27; 38(3): 328–336. PubMed Abstract | Publisher Full Text\n\nAlonso J, Liu Z, Evans-Lacko S, et al.: Treatment gap for anxiety disorders is global: Results of the World Mental Health Surveys in 21 countries. Depress. Anxiety. 2018 Jan 22; 35(3): 195–208. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStröhle A, Gensichen J, Domschke K: The diagnosis and treatment of anxiety disorders. Dtsch. Arztebl. Int. 2018 Sept 14; 155: 611–620. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPoorva: A study of association between early menarche and anxiety in undergraduate students. [Dataset]. OSF. 2024. Reference Source\n\nCuschieri S: The strobe guidelines. Saudi J. Anaesth. 2019; 13(5): S31–S34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThe Jamovi Project: Jamovi. (Version 1.x) [Computer Software]."
}
|
[
{
"id": "304527",
"date": "24 Jul 2024",
"name": "Gayatri Bhatia",
"expertise": [
"Reviewer Expertise Psychiatry",
"addiction",
"mental health in special populations",
"occupational 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\nThis study could have been more powerful if controlled for whether formal/informal guidance was received regarding pubertal changes, and support perceived during that time. Also, factors like family environment, temperament, history of traumatic experiences play a significant mediating role in this context. This study needs to address these factors, if not in methodology, atleast in discussion, limitations and future directions.\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": "12162",
"date": "09 Aug 2024",
"name": "Sharanya Shetty",
"role": "Author Response",
"response": "Dear Madam, Thank you for your valuable feedback on our manuscript. We appreciate your insightful comments and suggestions, which has undoubtedly contributed to improving the quality of our manuscript. We have tried our best to address your concerns in the modified manuscript. We understand the importance of controlling for formal/informal guidance received regarding pubertal changes and support. Though we had not controlled this in our study, we have carefully considered your suggestions and made revisions to the discussion part and included regarding the importance of guidance, communication and support during puberty. We appreciate your observations of the significant mediating role of traumatic experience that can play a major role. We have incorporated this in discussion highlighting its role in increasing the risk of anxiety. In addition to the above, we have also discussed on the role of social and cultural environment on puberty in the discussion section. The confounding factors like family environment, temperament, history of traumatic experience, guidance and support during puberty which were not explored in our study has been highlighted in the limitation section. We have also highlighted the need for these to be incorporated in the future studies. Thank you again for your valuable feedback and we will consider your suggestions for future research directions. Regards Dr. Sharanya B. Shetty Department of Psychiatry, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India"
}
]
},
{
"id": "304526",
"date": "30 Jul 2024",
"name": "Sanjeev Badiger",
"expertise": [
"Reviewer Expertise Public health",
"Infectious Diseases and non communicable 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 topic selected is novel , but more details could have added regarding matching. Other factors like socioeconomic conditions and environmental factors could have been added to avoid bias but this was mentioned in the limitation of the study Results and discussion part: satisfactory with good number of references Limitations of the study: Mentioned about the limitations\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": "12163",
"date": "09 Aug 2024",
"name": "Sharanya Shetty",
"role": "Author Response",
"response": "Dear Sir, Thank you very much for your review of our article. We are pleased to hear that you found our study to be novel. We appreciate your insightful comments and suggestions. Regarding your suggestion for considering factors like socioeconomic conditions and environmental factors for avoiding the bias, we acknowledge the importance of considering these factors and its impact on menarche and anxiety. Though we have mentioned about this in the limitations, we have made an attempt to discuss regarding social, cultural factors, guidance, communication factors in the discussion in addition to the limitations in the revised manuscript. In future research we plan to explore the influence of these variables to provide a more comprehensive understanding. We appreciate your positive feedback on results and discussion part and the limitations. Once again thank you for your valuable feedback and recognition of our contribution to understanding the association between early menarche and anxiety in undergraduate students. We will consider your suggestions for future research directions. Regards, Dr. Sharanya B. Shetty Department of Psychiatry, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India"
}
]
}
] | 1
|
https://f1000research.com/articles/13-807
|
https://f1000research.com/articles/13-281/v1
|
17 Apr 24
|
{
"type": "Systematic Review",
"title": "Osseointegrative and antimicrobial properties of graphene oxide nano coated dental implants: A systematic review",
"authors": [
"Sounyala Rayannavar",
"Sunil Kumar MV",
"Vignesh Kamath",
"Mahantesh Bembalgi",
"Namratha Nayak",
"Praveen Jodalli",
"Sounyala Rayannavar",
"Sunil Kumar MV",
"Mahantesh Bembalgi",
"Namratha Nayak",
"Praveen Jodalli"
],
"abstract": "Introduction Osseointegration stands as a pivotal concept within the realm of dental implants, signifying the intricate process through which a dental implant integrates with the adjoining bone tissue. Graphene oxide (GO) has been shown to promote osseointegration, the process by which the implant fuses with the surrounding bone. The objective of this study was to assess the osseointegrative and antimicrobial properties of GO nano coated dental implants.\n\nMethods A systematic search was conducted using electronic databases (e.g., PubMed, Scopus, Web of Science) to identify relevant studies published. Inclusion criteria encompassed studies that evaluated the effects of GO nano coating on osseointegrative and antimicrobial characteristics of dental implants. Studies not written in English and published before 2012 were excluded.\n\nResults The initial search yielded a total of 127 potential studies, of which six met the inclusion criteria and five were included in the review. These studies provided data on GO nano coated dental implants and their osseointegrative and antimicrobial properties. All the included studies showed moderate risk of bias. None of the studies provided information related to sample size calculation or sampling technique.\n\nDiscussion The findings from the included studies demonstrated that GO nano coating had a positive impact on osseointegrative properties of dental implants. Enhanced bone-implant contact and increased bone density were observed in animals and humans receiving GO nano coated implants. Furthermore, the antimicrobial properties of GO nano coating were found to inhibit bacterial colonization and biofilm formation on the implant surface, reducing the risk of implant-associated infections.\n\nConclusion The findings indicate that GO nano coating holds promise in enhancing the success rate and longevity of dental implants. However, more studies with larger sample sizes, are needed to further strengthen the evidence and determine the long-term effects of GO nano coated dental implants.",
"keywords": [
"Graphene oxide",
"dental implants",
"osseointegration",
"antimicrobial properties",
"systematic review"
],
"content": "Introduction\n\nOsseointegration stands as a pivotal concept within the realm of dental implants, signifying the intricate process through which a dental implant integrates with the adjoining bone tissue. This integration results in the formation of a robust and enduring foundation for the replacement tooth or teeth.1 This term is derived from the Latin words “Osseo” which means bone, and “integration,” which means to make whole.1 Osseointegration primarily depends on the implant placement, healing period, biocompatibility, stability, longevity and maintenance of the dental implant.2,3\n\nThe process of osseointegration begins when a dental implant, typically made of biocompatible materials like titanium, is surgically placed into the jawbone at the site of a missing tooth. This implant post serves as a replacement for the natural tooth’s root. Bio-activation as well as surface modification of titanium implants reduces an immune response and allows for successful osseointegration.4 Cobalt chromium alloys, Iron-chromium-nickel based alloys and ceramics were also used as dental implant materials. Titanium alloys and titanium alloys stays superior to the previous dental implants due to its excellent osseointegrative properties.5 While pure titanium implants and their alloys exhibit outstanding biocompatibility, mechanical strength, and chemical stability, they are associated with certain disadvantages, including delayed osseointegration and an extended period of post-operative healing. These factors can contribute to the potential failure of dental implants.6 To address these limitations, implant surface alterations using techniques based on the immobilisation of biologically active organic compounds has been discovered.7\n\nSurface coating of titanium dental implants is an essential aspect of implant dentistry, as it plays a crucial role in enhancing osseointegration, stability, and long-term success of the implant. There are several surface coatings and treatments that can be applied to titanium dental implants to improve their performance. Some of the commonly used surface coatings and treatments include: Anodic Oxidation (Anodization), Sandblasting and Acid Etching, Plasma Spraying, Blasted Surfaces, Titanium Nitride Coating, Zirconia Coating, Chemical Modifications.8\n\nSurface modifications using nanomaterials are widely used recently. These nanomaterials make good coating options for dental implants made of titanium (Ti-based) as it enhances implant fixation and encourages soft tissue integration and osteogenesis. In addition, osteoconductive nanoparticles creates a chemical bond with bone to ensure that implants are biologically fixed.9 In order to achieve better osseointegrative properties, naturally bioactive and antimicrobial polymers like chitosan and graphene oxide have been employed. By exposing bioactive modifications to simulated bodily fluids, specific cellular and tissue reactions can be induced, leading to biomimetic precipitation of calcium phosphate (CaP).10–12\n\nGraphene coatings stimulate osteogenic differentiation, cell adhesion, and antibacterial activity. Coating dental implants with graphene oxide can offer several potential benefits. Graphene oxide has demonstrated the ability to enhance osseointegration, the bonding process between the implant and the adjacent bone. The distinctive surface characteristics of graphene oxide promote enhanced bone adhesion, resulting in increased stability and prolonged success of the implant. Graphene oxide possesses antibacterial properties, which can help prevent infections around the implant site.13 Graphene oxide is generally considered biocompatible. This means it is well-tolerated by the human body and does not provoke a significant immune response. The high surface area and unique properties of graphene oxide can be harnessed for controlled drug delivery. This may allow for the local release of antibiotics or other therapeutic agents to further prevent infection and promote healing. Graphene oxide coatings can improve the visibility of dental implants in imaging techniques like X-rays or CT scans, aiding in diagnosis and follow-up care. The amalgamation of graphene oxide with other biomaterials can augment the surface properties of a material, impart antibacterial attributes, and influence cellular behavior.14,15\n\nVarious studies have been conducted to compare the osteogenic potential, physical properties and biologic properties of titanium dental implants with or without graphene oxide surface modification.16–18 As these comparative studies conducted are on different forms of surface coatings on titanium implants, the current systematic review aimed to examine and analyse osseointegrative properties of graphene oxide coated Titanium dental implants compared to conventional titanium dental implants without any surface modifications.\n\n\nMethods\n\nThe current review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.19 This review has been officially registered with PROSPERO and has been assigned the registration number CRD42023413883.\n\nWe performed an extensive search across multiple electronic databases, including PubMed, Scopus, Web of Science, and Embase, to identify relevant articles evaluating the osteointegration and biological properties of titanium dental implants coated with graphene oxide. The search utilized key terms such as “graphene oxide,” “titanium implants,” “osseointegration,” “surface roughness,” and “surface characteristics,” combined using Boolean operators “AND” or “OR” to optimize article retrieval. The inclusion criteria for this review encompassed studies published from January 1, 2012, to December 31, 2022, covering a span of 10 years. The rationale behind this timeframe was to focus on the recently emerged method of surface modification involving graphene oxide coating on titanium dental implants. Consequently, studies published before 2012 were excluded.18 The details of search strategy are mentioned in Table 1.20 Details of the studies were uploaded in figshare open repository and publically available.20\n\nThe studies included were in line with the PICO (Population, Intervention, Comparison and Outcomes) criteria21:\n\n• Population: Titanium dental implants\n\n• Intervention(s): surface modification of titanium dental implants with graphene oxide coating\n\n• Comparator(s)/control: Conventional implant or surface modification done with other materials such as chitosan\n\n• Outcome(s): Osseointegration and biological properties of Graphene oxide nano coated titanium dental implants.\n\nTwo reviewers (SR and VK) independently evaluated titles and abstracts to identify potentially suitable studies. Any uncertainties were resolved through discussion with a third reviewer (SK). The inclusion criteria for the chosen studies encompassed English language research articles with complete full-text manuscripts. Additionally, all in vitro studies, clinical trials, randomized clinical trials, comparative studies, and cross-sectional studies relevant to the topic were considered for inclusion, while case reports, case series, narrative reviews, and single-arm longitudinal studies were excluded. Abstracts without accompanying full-text articles were also excluded from the conduct and reporting of the present systematic review. Flowchart illustrating the process for inclusion of articles is illustrated in Figure 1.\n\nThe articles obtained following the literature search underwent scrutiny by the study investigators to eliminate duplicated or irrelevant studies. Subsequently, two reviewers (SR and VK) independently conducted further screening of the remaining articles to assess their eligibility for inclusion in the systematic review. For each study, the following factors were meticulously noted: Author name(s), study design, type of coating, method of coating, surface characteristics, mechanical properties, cell adhesion, and antimicrobial properties.20\n\nRisk of Bias assessment: The quality assessment of the studies included in the review was conducted using the QUIN tool specifically designed for evaluating the risk of bias in in-vitro studies.22\n\nThis tool assesses bias across 12 domains, encompassing clearly stated aims and objectives, a comprehensive explanation of sample size calculation, detailing of the sampling technique, information about the comparison group, methodology explanation, operator details, randomization process, method of outcome measurement, details of the outcome assessor, blinding, statistical analysis, and presentation of results.22,20\n\n\nResults\n\nThe current systematic review focused on determining whether osseointegration and the biological properties of graphene oxide nano coated titanium dental implants are superior to conventional or other nanomaterial-coated titanium dental implants. The study entailed a comparative analysis of contact angle and surface roughness between conventional/chitosan-coated titanium implants and graphene oxide-coated titanium implants.\n\nThe electronic search was conducted through three distinct stages. In the initial stage, a total of 127 articles were initially retrieved by employing specified keywords in the electronic databases. Two independent reviewers (VK and SR) conducted this search. The titles of the retrieved studies were then screened to ensure they met the eligibility criteria outlined by the PICO framework. Moving on to the second stage, abstracts of all selected titles were meticulously screened, and the complete texts of 39 studies deemed potentially pertinent were identified for the third stage. Notably, 33 studies were excluded at this stage as they assessed parameters beyond contact angle, surface roughness, and biocompatibility.\n\nIn the third stage, a detailed review was conducted on the complete texts of the 39 identified studies. Ultimately, 6 studies were selected for inclusion in this review.11,23–27 One of the reviewed articles exhibited a discrepancy in measurement presentation for outcomes (contact angle and surface roughness), resulting in the exclusion of these studies from the quantitative analysis11 (Table 2).\n\nEvery study included in the analysis demonstrated a moderate risk of bias. None of the studies furnished details pertaining to sample size calculation or the employed sampling technique. Details of blinding of the examiners was unclear in the included studies (Table 3).\n\n\nDiscussion\n\nGraphene oxide has recently demonstrated remarkable achievements in dentistry, spanning the treatment of oral cancer, regenerative dentistry, drug delivery, and antibacterial applications.25 Liu et al. (2011) conducted a review in the domain of oral disease treatment, emphasizing the potential application of graphene oxide as a restorative material for addressing dental caries. The review underscored the utilization of graphene oxide due to its superior physicochemical and mechanical characteristics. Furthermore, the study highlighted its compatibility with glass ionomer cements, demonstrating the capability to improve the mechanical properties of composites without compromising their aesthetic attributes or their ability to release fluoride.28\n\nGraphene and graphene oxide have demonstrated characteristics with potential anticaries effects, inhibiting the colonization of S. mutans and P. gingivalis. Moreover, these materials exhibit the capability to stimulate the differentiation and proliferation of human dental pulp stem cells (hDPSC) and stem cells from periodontal ligaments (PDLSC). This property is conducive to the regeneration of dental pulp and periodontal ligament tissues.27,29\n\nGraphene oxide finds extensive use in dental implants owing to its notable surface energy, mechanical strength, and biointegration properties. The incorporation of graphene in implants is primarily driven by its capacity to physically interact with biomolecules such as enzymes, proteins, or peptides. Graphene exhibits exceptional biocompatibility, efficiently stimulates and matures stem cells, and possesses long-term durability. Furthermore, the substantial surface area of graphene is a crucial aspect with significant potential for future bio-functionalization.28 Titanium implants are coated with both graphene oxide and reduced graphene oxide (rGO) showcased their inherent ability to induce osteogenic differentiation. This characteristic is of particular significance for the long-term success of dental implants in comparison to conventional surface treatments like grit-blasting, acid etching, and micro-arc oxidation.30,31\n\nThe analysis focused on studies that evaluated Osseointegration properties, utilizing available data from the selected studies, including contact angle and surface roughness. Additionally, the application of reduced graphene oxide as a surface coating in titanium implants was also explored. Both reduced graphene oxide and graphene oxide coating renders similar surface characteristics to the titanium implant. Other characteristics such as Raman Shift, surface energy and biologic properties (cell proliferation, Alkaline Phosphatase [ALP] activity and biofilm thickness were not assessed as the study results of these parameters were presented in different measurements (either in percentages or in abr units) and at different time duration. Hence the quantitative analysis of same was not performed due to the differences in data presentation. However, study by Shin et al.,2022 showed that reduced graphene oxide nanocoated titanium dental implants have high cell proliferation rate and ALP activity within 21 days.23 Cell attachment was also observed to be higher in reduced graphene oxide coated titanium implants. Kang et al., 2021 also reported a higher mineralization with reduced graphene oxide coated titanium dental implants.25\n\nQuantitative assessment of the selected studies was conducted to evaluate surface characteristics, specifically surface roughness and contact angle are represented in Figure 2 and Figure 3.20 In the comparison between Graphene Oxide-coated titanium implants and Chitosan/control implants, the latter exhibited a lower contact angle and higher surface roughness. These findings suggest enhanced adhesion to the periosteum. Notably, research has demonstrated that reduced graphene oxide coating, when combined with concentrated growth factors, facilitates the differentiation of implants into osteoblasts. This acknowledgment highlights its potential as a revolutionary material for altering dental implants and acting as a foundational structure for the regeneration of bone tissue.\n\nShin et al. and Kwak et al. suggested that increased rGO concentration on the surfaces of titanium implants leads to rougher surfaces capable of absorbing exogenous proteins, thereby promoting cell proliferation and osteogenic differentiation.23,32\n\nThe recognized antibacterial mechanisms of GO currently include the physical breakdown of the cell membrane and the induction of damage through oxidative stress. Generally, materials based on graphene are known to generate oxidative stress, primarily through reactive oxygen species, resulting in antibacterial effects and significant harm to bacterial cells.17 Another antibacterial mechanism of GO involves the dispersibility and trapping capacity of its oxygen-containing functional groups.33 In accordance with the insights from the review, the reduction of graphene oxide has been observed to enhance antibacterial capabilities by diminishing bacterial colonization on graphene oxide-coated titanium implants. Notably, a substantial enhancement in osseointegrative characteristics has been evident, as evidenced by elevated alkaline phosphatase activity and increased cell proliferation around the graphene oxide-coated titanium implants. These findings underscore the multifaceted benefits of optimizing graphene oxide configurations for improved antimicrobial and osseointegrative performance in the context of dental implants. The hydrophobic nature of graphene oxide plays a role in preventing bacterial cells from adhering to each other, and this hydrophobic contact can lead to the breakdown of the bacterial membrane, exerting an antibiotic effect.12,34,35\n\nThe expression of ALP, and extracellular matrix proteins such as RUNX2 and COL1A1 that promotes osteoblast differentiation appears to be improved by rGO as well.36 Several studies have shown that through the activation of the focal adhesion kinase (FAK)/P38 pathway, improved bone mesenchymal stem cells (BMSC) adhesion capacity, and proliferation, GO can trigger early osteogenic differentiation of BMSCs.37 Additionally, hMSC (human mesenchymal stem cells) adhesion, migration, and proliferation can be controlled by graphene oxide.38–40 Hence graphene oxide coated dental implants serves higher chances in success of dental implants due to its improved biological and mechanical properties compared to conventional/chitosan coated dental implants.41 Moreover, it is imperative to conduct clinical trials and studies to thoroughly evaluate the biocompatibility, mechanical properties, and long-term performance of graphene oxide-coated titanium dental implants, ensuring a comprehensive understanding of their advanced properties.\n\nConsidering the scarcity in in-vitro studies conducted in comparing the biological properties and antimicrobial properties of graphene oxide surface coated titanium dental implants, more studies could be conducted in future. Studies comparing graphene oxide coated titanium dental implants with other bioactive surface modification materials such as ceramic and composites would also determine the superiority of biological, mechanical and antimicrobial properties of graphene oxide surface coating.\n\n\nConclusion\n\nUtilizing graphene oxide as a coating for titanium implants creates a highly biocompatible surface, promoting enhanced integration with surrounding tissues and reducing the risk of rejection or complications. The exceptional mechanical strength and flexibility inherent in graphene oxide further contribute to the durability and longevity of the implants, ensuring not only effective integration but also sustained long-term performance. The success or failure of dental implants hinges on various factors, including implant location, the load-bearing capacity of the underlying bone, and the overall health of the patient.\n\nIn conclusion, the potential transformation of implantology is embodied in graphene oxide-coated titanium dental implants, driven by advancements in biocompatibility, osseointegration, antibacterial properties, and controlled drug delivery. Continued research and thorough scientific inquiry have the potential to position these implants as significant contributors to considerably improved patient outcomes, a reduction in complications, and an overall enhancement in the quality of life for individuals in need of dental implants.\n\n\nAuthors’ contributions\n\nAll authors contributed equally for this study and preparation of manuscript.",
"appendix": "Data availability statement\n\nAll underlying data are available as part of the article and no additional source data are required.\n\nFigshare: Osseointegrative and antimicrobial properties of graphene oxide nano coated dental implants: A systematic review, https://doi.org/10.6084/m9.figshare.25163666.v1. 20\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: checklist for Osseointegrative and antimicrobial properties of graphene oxide nano coated dental implants: A systematic review, https://doi.org/10.6084/m9.figshare.25163666.v1. 20\n\n\nReferences\n\nJayesh RS, Dhinakarsamy V: Osseointegration. J. Pharm. Bioallied Sci. 2015 Apr; 7(Suppl 1): 226–229. PubMed Abstract | Publisher Full Text | Free Full Text\n\nParithimarkalaignan S, Padmanabhan TV: Osseointegration: an update. J. Indian Prosthodont. Soc. 2013 Mar; 13(1): 2–6. Epub 2013 Jan 11. 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Interfac. 2022 Feb 1; 28: 101683–101683. Publisher Full Text"
}
|
[
{
"id": "289857",
"date": "27 Jun 2024",
"name": "Dinesh Rokaya",
"expertise": [
"Reviewer Expertise Prosthodontics",
"maxillofacial prosthetics",
"dental implants",
"dental materials"
],
"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 article where the authors did a systematic review to study the antimicrobial properties of graphene on dental implants. However, the methodology is not clear which needs clarification and improvement, especially the search strategy. The abstract needs improvement. Finally, the manuscript needs revision and English language improvement. Some comments on this research are as follows.\nAbstract\nThe method section is not clear. It is better to add details.\nIntroduction\nFor the line “Surface coating of titanium dental implants is an essential aspect of implant dentistry, as it plays a crucial role in enhancing osseointegration, stability, and long-term success of the implant”. Add reference [Ref -1]\nGraphene coatings stimulate osteogenic differentiation, cell adhesion, and antibacterial activity. Add reference [Ref-2]. In these lines, there are no citations, so I recommend to add one.\nAdd more to the statement with references “Graphene oxide coatings can improve the visibility of dental implants in imaging techniques like X-rays or CT scans, aiding in diagnosis and follow-up care.”\nMethod\nThe search strategy is confusing. Please add the total search search words used. In the Table 1, it is not good to mix the PICO and the search words. The authors can add PICO in a separate table.\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? 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": [
{
"c_id": "12152",
"date": "09 Aug 2024",
"name": "Vignesh Kamath",
"role": "Author Response",
"response": "Thank you for all the valuable comments. We have responded to all the comments provided by the reviewer and made the necessary corrections. The updates are as follows: Comment 1: Added the references suggested by the reviewer for the two sentences. Comment 2: Modified the search strategy as per the reviewer's suggestions. Updated and modified the reference list accordingly. All changes have been made using track changes, and the new version of the manuscript is submitted for your review. Thank You"
}
]
}
] | 1
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https://f1000research.com/articles/13-281
|
https://f1000research.com/articles/12-1364/v1
|
18 Oct 23
|
{
"type": "Research Article",
"title": "Factors contributing to online child sexual abuse in Bangladesh: A qualitative inquiry",
"authors": [
"Md Redwanul Islam",
"Muhammad Ibrahim Ibne Towhid",
"Marium Salwa",
"Anika Tasnim",
"Wai Wai Mroy",
"Md Maruf Haque Khan",
"Md Atiqul Haque",
"Md Redwanul Islam",
"Muhammad Ibrahim Ibne Towhid",
"Marium Salwa",
"Anika Tasnim",
"Wai Wai Mroy",
"Md Maruf Haque Khan"
],
"abstract": "Background: Children globally, including in Bangladesh, are facing various forms of online sexual abuse including sextortion, exploitation, body shaming, and blackmail. They are also coerced into engaging in intimate activities, harassed through the sending of sexual content, among other forms of abuse. We aimed to explore the root cause of online child sexual abuse (OCSA) in Bangladesh. Methods: This qualitative research design utilized in-depth interviews (IDIs) and key informant interviews (KIIs) between February and April 2022. The study sample comprised 21 school-going children aged 13−17 years, selected from two different geographical settings (10 from rural areas and 11 from urban areas) in Bangladesh using purposive sampling techniques. They participated in in-depth interviews (IDIs) while additional data was obtained through key informant interviews (KIIs) with 11 multidisciplinary stakeholders. Results: Children from both rural and urban areas reported facing abuse in various ways, such as being asked to send naked photos, being invited to be naked in video calls, and being invited to have virtual sex, among others, over the internet. Conclusions: We found inadequate internet literacy is a leading cause of OCSA. The causes of OCSA reported in this study is a serious public health concern in Bangladesh.",
"keywords": [
"Online Child Sexual Abuse",
"Root Cause",
"Health Problem",
"Children",
"Qualitative study",
"Bangladesh"
],
"content": "Introduction\n\nThe internet makes it possible for people to interact and communicate with one another instantly (Sethi and Ghatak, 2018). According to the Digital Global Report (Kemp, 2022a), 62.5% of people worldwide have internet access, and social media users comprise 58% of the world population. Globally, it is estimated that 75% of children aged 12−17 years use the internet regularly, mainly for education and entertainment purposes. Yet, despite its many beneficial roles, access to the internet exposes children to the risk of abuse, such as stalking, cyberbullying, blackmail, and sexual exploitation (UNICEF, 2022). According to a multi-country study conducted by UNICEF, 80% of children are exposed to online sexual abuse and cyberbullying (UNICEF, 2022).\n\nChildren experience abuse over the internet for several reasons, including inadequate parenting and lack of legal support (NCTSN, 2009; WHO, 2022), as well as inadequate knowledge of safe internet use and online abuse of children (OECD, 2020). However, extant research also shows that female children and those living in rural areas are comparatively more vulnerable to online sexual abuse (Fattah and Kabir, 2013).\n\nThis is particularly relevant for Bangladesh, as 60.3% of its approximately 167.1 million residents live in rural areas. Moreover, as Kemp (2022b) reported, approximately 30% of Bangladeshi population have internet access. Although it is expected that a large number of these internet users are children, it is difficult to estimate their exact number because most children use their parents’ electronic devices for accessing online content (Chahal et al., 2013).\n\nA UNICEF survey conducted in 2019 showed that around 32% of children aged 10−17 years in Bangladesh face cyberbullying and cyber harassment (Nabi, 2019; UNICEF, 2019). More recently, Mubassara et al. (2021) revealed that around 21% of rural children in Bangladesh received sexually explicit messages, while 17% received videos or pictures with sexual content. Available evidence further indicates that 56% of male and 64% of female children in Bangladesh face online sexual abuse (Ain o Salish Kendra, 2023).\n\nThus, online child sexual abuse (OCSA) is a growing problem in Bangladesh, but this issue is highly prevalent in other countries. Still, due to the paucity of studies focusing on the quantitative aspect of this problem (Shamim, 2017), evidence on the OCSA causes is limited. To address this gap in pertinent literature, in the present study, we aimed to identify the root causes of OCSA in Bangladesh.\n\nThe following theories constitute the theoretical framework to comprehend online child sexual abuse: the ecological model, the pathways model of child sexual abuse (Krug et al., 2002; Ward and Siegert, 2002).\n\nBelesky’s socio-ecological model explains the risk factors of child abuse, which are divided into four interrelated and mutually embedded levels: (a) individual, (b) relationship, (c) community, and (d) societal (Krug et al., 2002). This model may provide insight into the causes of OCSA.\n\nThe individual level focuses on personal factors such as personal history, behavior, and attitudes that increase the risk of becoming a victim or perpetrator. The relationship level refers to the influence of relationships with parents, partners, family members, and peers on behavior. The community level considers violence that occurs in schools, workplaces, and neighborhoods that increases the risk of becoming a victim. The societal level refers to the impact of social norms, values, and economic, political factors on society. Overall, the model identifies the process of violence from an individual level to family, community, and societal levels.\n\nThe pathways model of child sexual abuse proposed by Ward and Siegert (2002) partially explains the cause of online child sexual abuse in Bangladesh. The model encompasses five etiological pathways including intimacy deficits, deviant sexual scripts, emotional dysregulation, antisocial cognitions, and multiple dysfunctional mechanisms to explain possible offensive sexual behaviour. These pathways describe the combined relationship among emotional, psychological, and other mechanisms for understanding the preconditions of child sexual abuse. The first pathway suggests that offenders substitute children for adults due to intimacy deficits and self-esteem issues. The second pathway suggests that individuals with distorted sexual scripts may have dysfunctional relationship schemas that contribute to premature sexualization of children. The third pathway suggests that individuals with poor emotional regulation may use sex as a way to cope with their emotions. The fourth pathway suggests that patriarchal attitudes may contribute to child-adult sexual relationships based on the superiority of men in society. The fifth pathway involves pedophilic behaviors, where adults have an interest in engaging in sexual acts with children.\n\n\nMethods\n\nThe data for this qualitative study was obtained from 32 respondents, 11 of whom took part in key-informant interviews (KIIs) and 21 participated in in-depth interviews (IDIs). The demographic characteristics of the interviewees are presented below in Table 1. IDIs were conducted face-to-face with school-going children aged 13−17 in isolated places at their households, whereas KIIs focused on multidisciplinary professionals (child psychiatrist, psychologist, child rights activist, sociologist, lawyer, NGO professional, and Information and Communication Technology (ICT) teacher) and were conducted online via the Zoom platform. Due to the COVID-19 pandemic, participants were purposefully selected to ensure representation from rural and urban areas while maintaining homogeneity.\n\nTo reach out to both urban and rural children for IDIs, we purposefully selected Kadomtoli Thana (sub-district) of Dhaka as an urban area and Kamalgonj sub-district of Moulovibazar as a rural area. The study was conducted between February and April 2022.\n\nThe interview guides for KIIs and IDIs were designed based on three thematic areas: defining the problem, the causes behind the problem, and possible preventive strategies. A consultative meeting was held at the Department of Public Health and Informatics at Bangabandhu Sheikh Mujib Medical University (BSMMU) with public health experts, anthropologists, lawyers, child health specialists, and sociologists to outline the methodology and finalize the interview guides. The research team was comprised of experts from different academic backgrounds and research institutions, with credentials including PhD, MD, MBSS, MSS and LLB, which helped us investigate the issue from various angles. Pre-test interviews were conducted to finalize the interview guides, and the data from the pre-test interviews were excluded from the analysis.\n\nInterviews were conducted by the first author and three co-authors (M.R.I., A.T., M.I.I.T., and M.S.) including two males and two females, were engaged in all the interviews. Female children were interviewed by female researchers. The researchers introduced themselves to the interviewees to establish rapport and provide a brief overview of the study before commencing the interviews. The researchers also took into consideration potential biases and assumptions during the interviews.\n\nThe duration of interviews was 15 to 30 minutes for individual IDIs and 30 minutes to one hour for KIIs. Interviews were recorded with proper consent and transcribed verbatim immediately after the interview. Non-verbal expressions were also noted. The interviews were conducted until new information was obtained from the respondents. Once we observed repetition of information, we concluded the data collection process.\n\nThe interview transcripts were analyzed manually using qualitative content analysis methodologies, focusing on both the manifest and latent contents. To maintain a strong connection between the transcriptions and the conducted interviews, the interviewers transcribed the audio recordings verbatim into Bengali, the spoken language of Bangladesh. Three authors (M.R.I., A.T., and M.S.) simultaneously read the transcripts, reviewed them, and confirmed their accuracy for analysis. They were involved in the analysis process, firstly meaningful phrases relevant to the objective of the study were selected from the text as meaning units. In the subsequent steps, all condensed meaning units were coded and grouped into categories (Elliott, 2018), allowing an overarching theme to emerge. The depth and level of abstraction of both the manifest and latent content were open to interpretation (Graneheim and Lundman, 2004). While the analysis of latent content concentrated on revealing hidden meanings, the interpretation of manifest content tried to characterize the text’s evident and readily apparent aspects.\n\nEthical permission for conducting this study was granted by the Institutional Review Board of BSMMU, Dhaka (Memo no. BSMMU 2022/33115). The ethical approval and the purpose of this study has been clearly stated to the interviewees. Written permission was obtained from guardians to conduct interviews with children, and assent from the children was also obtained. In collecting data on children’ experiences of online sexual abuse, the safety and sensitivity of all youth participants were taken into account during the interviews and throughout the entire research process. Prior to commencing each interview, children were informed that they could terminate the interview at any time and skip any questions they did not wish to answer. Their parents were fully informed about the focus of this study on child abuse and the inclusion of emotionally charged questions that their children can find distressing. They were also advised that their children could opt out of participating in the interview at any time. Nonetheless, to avoid upsetting or re-traumatizing the participants, interviewers did not directly ask them about their own experiences of online sexual abuse. In addition, participating children were encouraged to seek support from a trusted adult if they felt uncomfortable during the interview, and the interviewers completed each interview by asking how participants felt. However, none of them were uncomfortable after completing the interview.\n\nChild. We considered a child as a person aged up to 18 years, adopting the same definition of a child as outlined in the United Nations Convention on the Rights of the Child.\n\nOnline abuse. Online abuse is regarded as an extension of traditional forms of abuse that takes place in cyberspace, allowing perpetrators to hide behind screens. It involves willful and repetitive behaviors that have psychological consequences (Agatston et al., 2007) and serve as a means to express social aggression through electronic communication devices (Çetin et al., 2011). This term encompasses various forms of abusive interpersonal behaviors, including online bullying, stalking, sexual solicitation, and problematic exposure to pornography (Mishna et al., 2014).\n\nOnline sexual abuse. It includes two separate expressions as sexual solicitation and sexual interaction. Receiving a request from a perpetrator to provide sexual information or engage in sexual activities is referred to as sexual solicitation, whereas sexual contact is defined as actively engaging in sexual actions online (Baumgartner et al., 2010).\n\nCyberbullying. Cyberbullying, also known as electronic bullying or online social cruelty (Agatston et al., 2007), includes ‘willful and repeated harm inflicted’ (Hinduja and Patchin, 2008) toward another. Cyberbullying is unique in its use of electronic communication technology as the means through which to threaten, harass, embarrass, or socially exclude (Hinduja and Patchin, 2008; Cook et al., 2007; Patchin and Hinduja, 2006). Cyberbullying (CB) is a form of interpersonal aggression that occurs through electronic means, such as texting, online chats, or social media websites (Olenik-Shemesh et al., 2017).\n\nSexting. Sexting is sending, receiving, or forwarding sexually explicit messages, photographs, or images, primarily between mobile phones, of one to others. It may also include the use of a computer or any digital device (Van Ouytsel et al., 2017).\n\n\nResults\n\nThe main theme that emerged from the analysis is inadequate internet literacy as the root cause of online child sexual abuse (OCSA) in Bangladesh, which is also reflected in the categories. The following three categories resulted from the analysis: (a) the adventurous nature of children, (b) dysfunctional parent−child relationship, and (c) social and structural inadequacy (Figure 1). As each subcategory helps to establish the causes of OCSA, they shed light on how OCSA should be viewed from a socio-cultural point of view. Each category consists of 4 to 9 subcategories.\n\n1. Roaming the internet and social media sites\n\nThe availability of internet-enabled devices, such as smartphones, tablets, laptops, etc., encourages children in both rural and urban areas that have internet access to spend more time online. They explore different social media sites and, as they do not know who is on the other side of the internet, they can easily fall into the abuser’s trap. According to a female respondent:\n\n“I have many friends on Facebook, but some have bad motives and can do the worst things. My friend shared her personal information with an unknown person and her Facebook account was hacked. Afterward, the hacker irritated her by asking for more nude images or else the hacker would make her photos viral.”\n\n-(IDI-18, Grade 9)\n\n2. Befriending the unacquainted\n\nAs children may utilize different social media platforms such as Facebook, Messenger, WhatsApp, Instagram, Snapchat, Viber, etc., this can have both positive and negative impacts on their lives (Soniya, 2017). While one of the known risks of such online presence is excessive use of electronic devices, internet use also allows perpetrators to collect children’s contact details from the recharge shops and attempt to befriend them online. They would subsequently irritate children through online audio and video calls. On this issue, a child psychiatrist noted:\n\n“The perpetrator gets close to a child by posing as a good friend and gradually starts abusing the child. Perpetrators often collect victims’ contact numbers from recharge shops and search for them on Imo, WhatsApp, and other social media. Children, without understanding the consequences, chat out of curiosity.”\n\n-(KII-07, Child Psychiatrist)\n\n3. Engaging in online relationships and blackmail\n\nChildren who engage in romantic relationships through the internet are at risk of becoming victims of sexual abuse, as perpetrators who have developed an online relationship with them may pressure them to share nude photos or even insist on physical relationships, as stated by an ICT expert.\n\nEven if a youth shares personal documents just once, there is a risk of being abused, given that perpetrators may threaten to publish private relationships in front of family members, classmates, society, etc., if the victim refuses to comply with their requests. When in love, children may sometimes share their personal/intimate photos and videos with their romantic partners online, without realizing that these can be later used for blackmail. As noted by an informant:\n\n“I became engaged in a love affair with one of my classmates. Due to the pandemic, our love affair continued online. As time went by, he started asking me to share nude images. I refused to share any images online, but eventually, he started blackmailing me. He threatened that he would inform my family members about our love affair. He said that he would present me in a negative way to my family. There were only two choices left: listen to him or commit suicide.”\n\n-(IDI-18, Grade 9)\n\nAccording to the respondents, when a child becomes a victim of abuse, they are often blamed for the abuse rather than being supported, as people tend to think that the victim must have done something wrong to provoke the abuse. This was aptly surmised by a rural Grade 9 female informant who stated:\n\n“I kept my relationship hidden from my family members because my family is conservative and would take away my mobile phone if they knew I used it for social media access. After a few months, we broke up as the relationship was no longer working. But then, my (ex-boyfriend) started blackmailing me. As a result, I started experiencing deep depression. The family members came to know some of the details, and they accused me. They cursed me and said I should die to avoid causing further damage to their reputation and honor.”\n\n-(IDI-18, Grade 9)\n\n4. Curiosity\n\nEasy internet accessibility increases children’s curiosity to explore new things online, but it also elevates the risk that they may become involved in harmful activities. According to one of the interviewed:\n\n“Children can easily buy an internet package for unlimited social media usage with as little as 10 Bangladeshi taka (equivalent to 0.1 USD). These unlimited internet packages come with a limited-time offer from mobile phone operators. Children have a tendency to become involved in the internet and engage in unnecessary activities, which also leads to an addiction to viewing pornographic content and opens the door for sexual abuse.”\n\n-(KII-08, ICT Teacher)\n\n5. Masking identity\n\nAbusers’ ability to easily mask their identity increases the likelihood that children would fall into abusers’ traps or even start abusing others by modeling harmful behaviors they witness online. Many perpetrators targeting children create fake social media profiles, such as Facebook IDs, using female names and photos, and start disturbing the friends of the actual user through fake accounts. Perpetrators also blackmail the victim for money with personal photos and videos. Such proliferation of fake Facebook accounts makes it impossible for youth to verify which account is genuine. Children may also become abusers by learning from vulgar comments they read in different online Facebook groups. On this issue, one of the participating ICT teachers commented:\n\n“Children are creating fake social media accounts and are using them to irritate others. Yet, we have no surveillance system in our country, indicating that an urgent need to improve the intelligence software to monitor children.”\n\n-(KII-08, ICT Teacher)\n\n6. Lack of conscience\n\nChildren often share personal information (including revealing images) with their romantic partners online to show off, while also seeing this as a way to gain trust and assurance of commitment in their relationship. However, most are unaware that this creates a threat of sextortion, given that the person they consider their partner may start abusing their trust and demand nude photos. It is also not uncommon for those in a relationship to give their partner access to their social media account. The difficulties that may arise as a result were outlined by a female respondent from a rural area in Grade 10 as follows:\n\n“My ex-boyfriend asked me to send my nude photo just once as evidence of our relationship and proof that I love him. I was so much in love with him that I sent him the picture. When we were in a relationship and while we saw each other in person, he used to check my mobile phone and get access to my Facebook ID and password. I later tried to change my ID and password, but I was unable to do so.”\n\n-(IDI-21, Grade 10)\n\nChildren often fall into such traps as they do not appreciate that sharing personal information might be dangerous for them. This is particularly problematic when they are in romantic relationships, as they feel connection to their partners and see no harm in sharing inappropriate photos, videos, and other personal information with the loved one. Yet, if the relationship fails, the other person may use this personal information to threaten or humiliate them.\n\n7. Non-disclosure of abusive events\n\nWhen children become victims of online sexual abuse, they rarely report these incidents due to shame and worry that people (including their parents) will blame them instead of supporting them or trying to solve the problem. The victims also remain silent out of fear that their identity will be disclosed by the perpetrator and they will be embarrassed in front of their friends, relatives, and family members. That is why most cases of OCSA remain unreported.\n\n8. Temptation\n\nPerpetrators often tempt children to start communicating with them by offering gifts, jobs, outings, or visits to a restaurant, or enticing them in some other way children would find appealing. On this topic, one of the participating ICT teachers stated:\n\n“Perpetrators abuse children with power influence. If you cannot stop power influence, you cannot stop child abuse. Children with the support of their influential parents at times develop an attitude that they can do whatever they like and nobody can punish or stop them. Some parents even shelter their children from harmful activities rather than stopping them from engaging in abusive events.”\n\n-(KII-06, ICT Teacher)\n\n9. Victim as perpetrator\n\nChildren who have experienced sexual abuse and were not provided adequate support are likely to start tolerating such abuse and even become perpetrators. As one of the respondents took part in our study observed:\n\n“When a child is sexually abused and tolerates it, there is a strong possibility that the child might abuse another child. In addition, children who see pornography want to fulfill their needs by abusing others.”\n\n-(KII-07, Child Psychiatrist)\n\n1. Parent−child interaction\n\nThe professionals that served as key informants in this study concurred that, as parent−child interaction in Bangladesh is generally poor, children are at an increased risk of OCSA. Unfortunately, most parents do not find spending quality time with their children and trying to understand them very important. In addition, as the Bangladeshi society discourages discussions related to sexual events within the family, children often turn to the internet to satisfy their curiosity, which exposes them to the potential abuse. According to one of the interviewed ICT teachers:\n\n“Children hide the worst experiences because they are unable to discuss abusive events with their parents due to poor child−parent interaction. In some cases, children cannot tolerate the negative experience and attempt suicide.”\n\n-(KII-08, ICT Teacher)\n\n2. Quality time together\n\nSome parents spend time with their children, but this may not be a quality time, as parents rarely engage with their children as friends. This barrier in the parent−child relationship makes it difficult for children to confide in their parents and report any abusive events, although they have the urge to share. Still, as noted by an urban female participant in Grade 10, some children have positive relationships with their parents:\n\n“My friend was harassed by her ex-boyfriend. The boy shared my friend’s images on Facebook. I asked her to share this event with her parents, and eventually, she did. Her family supported her and also brought the situation under control.”\n\n-(IDI-21, Grade 10)\n\n3. Trust, understanding, and respect\n\nMost respondents stated that trust and respect are essential in the parent−child relationship, which is lacking in most Bangladeshi families. As a result, children do not have the opportunity to share abusive events with their parents because they do not have a trustworthy, understanding, and respectful relationship with their parents. As noted by a respondent:\n\n“I told my parents I was going through a traumatic situation, but they were not sympathetic. My mother even told me to commit suicide and said my abuse event was a disgrace to our family.”\n\n-(IDI-18, Grade 9)\n\nIn Bangladesh, the relationship between parents and children is often strained, as parents do not understand their children, as explained by one of the respondents who participated in this study:\n\n“A girl called me and said she was traumatized because her boyfriend disclosed their intimate pictures on social media. Her parents came to know about it and started beating her instead of trying to understand her. She called me to seek help and see if I could control the situation.”\n\n-(KII-11, Sociologist)\n\nYet, even when children report abusive events to their parents, they do not take steps to protect against abusers due to social shame, as explained by the child psychiatrist that served as one of our informants:\n\n“The parents of a female child brought her for psychological counseling. She was sexually abused online by her private tutor, which the family members later revealed. She did not initially share anything with the family members as she was not close with her parents. However, the girl’s family members found certain odd changes in the girl’s behavior. She wanted to be left alone and stopped interacting with other family members. She was disturbed all the time and even urinated in bed. The parents did not want to take any legal action against the boy. They thought taking legal action would be a hassle for the family and they would be harassed, which would damage their reputation.”\n\n-(KII-07, Child Psychiatrist)\n\n4. Parental knowledge and supervision\n\nAccording to our study respondents, Bangladeshi parents over the age of 40 are not well equipped to use the internet and are not accustomed to using modern technologies. As a result, they cannot even imagine that their children could be abused online. Sometimes, as parents have no knowledge of the scope of online content, they do not know which websites are helpful to their children, let alone how to prevent their children from accessing harmful websites or meeting unwanted friends, fraudsters, and perpetrators online. Consequently, they are incapable of making their children aware of safe internet use. Children are also unwilling to share their negative experiences as they believe their parents cannot protect them from something they do not understand, as explained by a key informant interviewee:\n\n“Parental ignorance is a cause of OCSA. Due to their lack of internet knowledge, parents cannot protect their children in terms of internet difficulties. There is some parental control software, but guardians do not know how to use it. Parents give their children smartphones but do not even care what websites they visit or who they meet online.”\n\n-(KII-06, ICT Teacher)\n\nDuring the initial months of the COVID-19 pandemic, all classes were conducted online, children had to use the internet to participate in school activities. Whether or not children used their own or their parents’ devices, many parents did not monitor their children’s online activities. However, it is well known that spending more time online increases the chances of interactions with unknown and anonymous users, thus exposing them to potential abuse.\n\n1. Child protection network\n\nAccording to Children Act 2013 of Bangladesh, every upazila (sub-district) and even the union (lowest administrative unit) is supposed to have a child protection network. In addition, a committee comprising children, parents, teachers, and local government representatives is supposed to be formed, allowing victims to come forward to report incidents of abuse through a child representative. However, only a few such committees and networks have been established. Even when such committees exist, they do not function properly, and no child representative is available for underage victims of abuse. According to one of the NGO workers that participated in the interviews:\n\n“NGOs are trying to ensure that child representatives are included in the child protection committees to enhance the anonymous reporting system. However, although child protection networks were supposed to be formed at the union, upazila, and district levels, during our field visits, we found that the committees at those levels were not properly functioning.”\n\n-(KII-01, NGO Professional)\n\nThis issue is further exacerbated by the fact that, even though some laws in Bangladesh directly or indirectly address protection against child abuse, they are not adequately implemented in practice.\n\n2. Administrative support\n\nUnfriendly administrative support prevents children from disclosing abusive events. As a result, victimized children cannot obtain proper support, as explained by one of the NGO workers that participated in our study:\n\n“The country has hundreds of laws, but perpetrators are not punished as there is a lack of implementation. Sometimes, the offender is released from jail through bribe, absence of witnesses, social support, or power.”\n\n-(KII-01, NGO Professional)\n\nMany children are also unaware that they can get support from government hotline numbers. On the other hand, victims rarely complain to the police because the process in Bangladesh is not child friendly, as explained by an informant:\n\n“I was not aware of the government hotline numbers. As my family was not supportive while I was abused, I could not go to the local police station to seek support as I needed to be accompanied by a guardian.”\n\n-(IDI-18, Grade 9)\n\n3. Pedophilic behavior\n\nPedophiles take pleasure in inflicting sexual abuse on children and some intentionally join child-based organizations to abuse children. Nonetheless, according to one of the interviewed NGO professionals, they often remain undetected in society:\n\n“Some pedophiles join child-based organizations with the intention of getting close to children easily. They collect all the information about children from the files and computers and target the vulnerable ones for abuse.”\n\n-(KII-02, NGO Professional)\n\nIn some cases, pedophiles are relatives or very close friends of the child’s family. This implicit trust makes the children particularly vulnerable, as explained by one of our informants:\n\n“If a pedophile is a relative, it is difficult to protect the child. People usually rely on relatives to take care of their children. As parents do not know who a pedophile is, individuals they trust can abuse their children without being discovered.”\n\n-(KII-02, NGO Professional)\n\nIn our cultural context, although this type of behavior is disrespectful to parents, they hide rather than disclose the abusive event.\n\n4. Known perpetrator\n\nOur key informants concurred that perpetrators are usually known to the child, as being a family member, friend, or a relative gives them access to all the personal details they need to lure the victim into their trap. In addition, parents would never suspect a known person of abusing their children. One of the interviewed ICT teachers referred to the situation one of her students faced, as she was sexually abused online by her brother-in-law but could not avoid him because they lived in the same house:\n\n“A female student in grade 10 came to me with a complex situation that had been going on in her life. She lives with her sister for educational purposes. Her sister’s brother-in-law added her on Facebook and started asking her personal questions that offended her. All his conversations and gestures around the house indicate that he is interested in becoming physically involved, yet she feels that she cannot confide in anyone. She is afraid that if she told her sister, her sister’s marital life might be jeopardized. She cannot leave their house either because she has nowhere else to go. If she goes to the home village, she will be married off early and will not be able to continue her studies.”\n\n-(KII-08, ICT Teacher)\n\n5. Social stigma\n\nChildren are raised with many societal stigmas, such as the internet being harmful and internet platforms being bad, among others. Yet, as they often use it secretly, they cannot ask their parents about the proper use of the internet, as explained by one of the respondents:\n\n“Bangladeshi children grow up in an environment promoting harmful social norms and traditions. This environment eventually contributes to online child sexual abuse.”\n\n-(KII-06, ICT Teacher)\n\nThe cultural norms within families in Bangladesh encourage abused children to remain quiet, as the social structure in our country does not condone open discussions related to sexual events.\n\n6. Availability of online sexual content\n\nOur informants noted that, as sexual content is widely available online and is shared freely in various social media groups, this increases the risk of OCSA. In most cases, perpetrators harass children by sending sexual material such as vulgar text messages, nude photos and videos on Facebook, Instagram, Snapchat, and other social media platforms, but children do not know how to stop such intrusive behavior. Some of the perpetrators also have access to the dark web, allowing them unsupervised access to a variety of sexual content. On this, a respondent stated:\n\n“People add me to many messenger groups that are full of sexual content. Even if I remove myself from one group, someone else adds me to another group. I do not want to join these groups intentionally.”\n\n-(IDI-21, Grade 10)\n\nAs indicated above, in many cases, children automatically receive sexually explicit content from various online sources, as there is no strict barrier to such access. On this issue, one of the participating ICT teachers commented:\n\n“Many children complain to us (teachers) that they receive unwanted site links on the internet, which irritates them. There is no specific protection on the internet for children. Children are vulnerable and behave abnormally after seeing these contents unintentionally. Children who see pornographic videos suffer from mental disorders.”\n\n-(KII-08, ICT Teacher)\n\n7. Lack of outdoor games\n\nAs open spaces for parks and playgrounds are scarce in cities, urban children do not get enough opportunities for outdoor games. Consequently, they are compelled to spend more time online for making friends, entertainment, and recreational activities, which increases their vulnerability to online abuse. According to a lawyer we interviewed:\n\n“Rural children have access to open spaces more than urban children. On the other hand, urban children have a wide availability of entertainment activities online, and they prefer to spend their time on the internet. However, even rural children want to make friends and spend time online because it has become more attractive than playing on the field.”\n\n-(KII-05, Lawyer)\n\n\nDiscussion\n\nIn this study, inadequate internet literacy has been identified as the root cause of online child sexual abuse (OCSA) in Bangladesh. While OCSA occurs in the virtual world, the existing social system plays a significant role in either increasing or reducing abuse (Khondkar, 2021). Furthermore, we found that victims are unable to reveal their abusive events to those close to them due to social constraints. Social constraints are defined by society as unwritten patterns of behavior that adhere to social groups, shaping people’s behavior based on their sex and social conditions from an early age (Johnstone, 2015; StudySmarter, 2022).\n\nBased on the findings of this research, it has been determined that perpetrators engage in harassing children through various means, such as sending vulgar texts, nude photos, videos, and making online audio and video calls.\n\nAs most perpetrators hide their real identities during online interactions (Arfini et al., 2021) allows them to remain undetected. On the other hand, children do not feel free to disclose sexual events to their parents due to societal taboo surrounding such topics in Bangladesh. This issue is further exacerbated by the dismissive parenting strategies (Deblinger and Runyon, 2005). Additionally, the UNODC (2020) highlights that many incidents of child sexual abuse go unreported to the police due to children’s fear of embarrassment in front of their friends, parents, and society.\n\nWe also found that the victims are reluctant to disclose their abusive experiences to legal authorities due to lack of a child-friendly legal system in Bangladesh.\n\nThis perspective is supported by the observations made by Warren (2019), indicating that the legal and administrative support for child sexual abuse fails to fully protect children, with no provision for anonymous reporting in Bangladesh. In fact, participants in this study identified the absence of anonymous reporting as a significant factor contributing to child sexual abuse.\n\nThe Government of Bangladesh has enacted several laws and regulations to combat and control OCSA, including the Prevention of Domestic Violence Act of 2010, the National Child Labor Elimination Policy of 2010, the National Children Policy of 2011, the Pornography Control Act of 2012, the Human Trafficking Deterrence and Suppression Act of 2012, and the Children Act of 2013. However, the improper implementation of these laws contributes to the growing prevalence of OCSA in our society (Shamim, 2017).\n\nOur findings further substantiated the prevailing notion that the child-parent relationship in Bangladesh is often strained. This issue, however, appears to be prevalent worldwide, as highlighted by Radford et al. (2015), who found that 50% of female children globally experience sexual abuse but never disclose it to anyone, and 7 out of 10 never seek help.\n\nTo address this growing social problem, the High Court of Bangladesh enacted legislation in 2022 requiring parents not to force their children into anything against their will in order to bring them up with positive attitudes (The Daily Star, 2022). Nonetheless, the persistent gap in the parent-child relationship, as revealed in our study, renders children susceptible to OCSA.\n\nOur findings revealed that if a child experience sexual abuse and tolerates it, there is a strong probability that the child will go on to abuse another child. This observation aligns with research from PsychCentral, which states that children who have been sexually abused often exhibit abnormal behaviors that can increase their vulnerability to further abuse or potentially lead them to become abusers themselves (PsychCentral, 2022).\n\nThere is a common belief in Bangladeshi society that “good things happen to good people, and bad things happen to bad people” (Gravelin et al., 2019), which leads to victims being frequently blamed for the abuse they have endured. The theory of victim-blaming posits that victims bear partial or full responsibility for their own suffering, hardships, and other misfortunes (Criminal Justice, 2022). Similarly, findings from the University of New Hampshire’s Crimes Against Children Research Center indicate that parents are more inclined to attribute blame to their children for the consequences of abuse, rather than holding the adults accountable (Wright, 2012).\n\nThe study revealed that female children are the most frequent targets of online sexual abuse, yet parents tend to blame their daughters despite knowing that their children are not at fault. Additionally, our findings indicated that children endure severe psychological and physical consequences following online sexual abuse. According to the Council of Europe, young girls are especially vulnerable to sexual exploitation, abuse, and bullying by their peers in online environments. They may also exhibit physical symptoms and develop mental illnesses, such as a desire to isolate themselves and distance themselves from others (Council of Europe, 2022).\n\nOnline child sexual abuse (OCSA) has emerged as a significant public health concern in Bangladesh, often stemming from romantic relationships with individuals met online (Nova et al., 2019). In fact, a longitudinal study conducted by Hébert et al. (2017) in Quebec revealed that 33% of the participating youth reported experiencing psychological violence within online romantic relationships. The authors further noted that victimized children encountered three times more psychological violence compared to non-victimized children. Our own findings align with this, as we discovered that children engaged in romantic relationships are more vulnerable to abusive situations. Perpetrators can exploit the private nature of chats by capturing screenshots, saving photos and videos, and later using them for online sexual abuse. The Australian government’s research findings support this, highlighting that children in romantic relationships often face image-based abuse, such as the circulation of nude photos or screenshots of sexually explicit content (YLE, 2018). Additionally, children are frequently coerced into sharing nude photos and videos through threats.\n\nOur analyses also indicate that relatives or close friends of the child’s family pose a particular risk, as the implicit trust in these individuals reduces the likelihood that pedophiles would be suspected of abuse. According to Tuli (2017), male pedophiles are more common than females in Bangladesh. On the other hand, in Europe, pedophiles tend to find their victims online. Yet, police investigations have also shown that pedophiles exist in many settings and even work at child-focused organizations (YLE, 2018), supporting the findings obtained in the present study.\n\nThe study further revealed that Bangladeshi children are not well-equipped to use the internet safely. According to UNICEF (2019), children who engage in a various online activities require more developed internet skills, but children of low-income countries like Bangladesh do not have enough opportunities to gain proper knowledge of digital technologies. Moreover, Bangladeshi parents themselves lack knowledge about safe internet use, and are unaware of how perpetrators can exploit children via online platforms, they cannot protect their children. Although there are several parental control software tools available, parents are not adequately trained to utilize them (UNICEF, 2019).\n\nThe similar findings revealed that children are abused due to a lack of understanding of internet use and the consequences of exploring the dark web (Saprea, 2022). In an earlier study, Madden et al. (2006) proposed that children need more training on how to use the internet as a source of information that can keep them safe from being sexually abused online.\n\nWhile agreeing with these observations, our study also revealed that excessive and unnecessary social media use contributes to OCSA. Children’s presence on various social media platforms such as TikTok, Facebook, Messenger, WhatsApp, Instagram, Snapchat, and others, may expose them to online sexual abuse by known and unknown individuals (Kopecký and Szotkowski, 2018; Lovejoy, 2021). Although Facebook authorities have imposed some terms of service (ToS) restrictions on users under the age of 18, in practice children cannot be prevented from opening a Facebook account, as they can manipulate information to open an email ID (Hargittai et al., 2011). According to Kopecký and Szotkowski (2018), who conducted their study in Czech Republic, 66% of perpetrators use Facebook as a sexting platform. Similarly, O’Keeffe and Clarke-Pearson (2011) found that children are encouraged to engage in harmful activities by social media content such as movies, dramas, series, and so on, which influence children to have unusual relationships, drink alcohol, engage in sexual affairs, live together, and partake in a variety of inappropriate behaviors.\n\nUsing the internet has many benefits for children. Still, when children have easy access to internet-enabled devices like smartphones, tablets, laptops, etc., this encourages them to use the internet more often, thus increasing the risk of online sexual abuse (Debroy, 2015). We also found that some children are addicted to watching pornography, and this may cause them to lose their moral values and suffer from a variety of health risks as well as mental disorders (Baxter, 2014).\n\nOn the other hand, when 11- to 16-year-olds are prohibited from spending excessive time on their mobile phones, their academic scores improve (Keeley and Little, 2017). Furthermore, as noted by our informants, insufficient space and safety for outdoor entertainment for urban children causes them to spend most of their free time online. This may cause a range of problems as children need physical activities that contribute to their mental and physical well-being, and develop skills such as group work, teamwork, and leadership qualities, but their outdoor activities have declined over the years due to safety concerns (Kalpogianni, 2019). Similarly, it was found that the lack of outdoor entertainment is damaging for children’s health and well-being (Bento and Dias, 2017).\n\nWe found that school dropouts and unemployed youths are more likely to become abusers because they spend most of their free time on the internet exploring unnecessary things. According to UNODC (2020) economic insolvency among youths, tend to develop bad attitudes and hang out with people who have bad traits, which in turn refrains them from developing good social norms and attitudes.\n\n\nConclusion\n\nAs OCSA is an emerging issue, it has remained relatively unexplored in Bangladesh until now. Our investigations revealed that inadequate internet literacy is the leading cause of OCSA in the country and has many adverse effects on physical and mental health of children. It was found that both urban and rural children use internet devices and face online sexual abuse. Therefore, the government of Bangladesh needs to effectively implement specific laws to combat and control OCSA to enhance internet safety for both children and parents.\n\nThis qualitative study, investigating factors contributing to online child sexual abuse, is the first of its kind conducted in Bangladesh. The inclusion of participants from both urban and rural areas, as well as potential experts from relevant sectors, is a strength of this study.\n\nWhile traditional interview studies carry a reliability risk by merely focusing on verbal meaning (Finnegan, 2003), this study mitigates such risks by incorporating analysis of the latent meaning (Krug et al., 2002).\n\nThis study has several limitations that need to be acknowledged. Firstly, as the participants were children, there is a possibility of hidden abusive events or expressed unreal experiences due to the chance of disclosure to others, fear of humiliation and shame. Nova et al. (2019) explained that victims often remain silent about their abusive events due to being insulted or humiliated by their friends and family members. To encourage children to express themselves, we assure maintaining the privacy of all information, and only the research team members will have access to the data. Moreover, we assure them that their name will not be mentioned anywhere in the research documents.\n\nSecondly, this study was conducted in two out of the 64 districts of Bangladesh, hence limiting the generalization of the findings. However, within the group of interviewees, we found data saturation, leaving us with no option to increase the sample size.\n\nThirdly, Bangladesh, being a densely populated country with 1265 people living in one square kilometer area (Worldometers, 2023), poses difficulties in managing isolated places for interviews, especially in urban areas. Due to the overcrowded environment, conducting in-depth interviews (IDIs) in secluded locations was not always feasible. Furthermore, conducting interviews in separate places often sparked curiosity among family members, leading them to eavesdrop on the conversations, which disrupted the interview environment in some instances. However, our data collectors were properly trained to handle such situations by politely requesting the curious individuals to allow them 30 minutes of uninterrupted time with the interviewee. Additionally, to ensure cultural sensitivity, we engaged female data collectors for interviewing female children.\n\nFourthly, this study is one of few significant qualitative studies conducted in Bangladesh. Consequently, when supplementing the field data with input from relevant experts, there is a possibility of obtaining biased information. To address this risk, we took measures to include a diverse group of stakeholders, such as child psychiatrists, sociologists, child experts, teachers, and guardians.\n\nFifthly, the retrospective nature of the data in this study presents a potential challenge as the interviews focus on events from the children’s past, which may introduce recall bias. However, it is widely recognized that memories of events that evoke strong emotions tend to be well retained in the mind.\n\nSixth, obtaining permission from the children’s parents reduced control over the first presentation of the research to the child, possibly exposing them to outside influences. It is worth emphasizing, however, that child abuse is generally accepted as a disciplinary method by adults in Bangladesh. This cultural acceptability fosters an environment in which discussing and exposing such topics is not considered taboo.\n\n\n\n1. Online child sexual abuse (OCSA) is an emerging problem that has severe and detrimental effects on the physical and mental well-being of children. However, it remains relatively unexplored in Bangladesh.\n\n2. The root cause of OCSA in Bangladesh is inadequate internet literacy, highlighting the urgent need for educational interventions.\n\n3. The absence of laws to regulate OCSA in Bangladesh emphasizes the public health concern surrounding online child sexual abuse.\n\nThe government of Bangladesh should include OCSA as a topic in secondary-level and higher-secondary-level education and should provide support for initiatives aimed at improving the internet literacy of the relevant stakeholders, including children, parents, teachers, and policymakers. The government should also take steps to make the overall internet space safe for children through scrutiny of all published content, including texts, images, and videos that children access. The government also needs to support outdoor sports and other activities for children. At the community level, awareness campaigns need to be initiated about safe internet use, mainly focusing on children and parents. Moreover, there should be a reporting system where children can anonymously report incidents of abuse. The media can play a vital role in reducing OCSA through mass awareness programs. The Children’s Act in Bangladesh needs to define and address OCSA and strict legal measures against the perpetrators of OCSA need to be ensured to protect children from abuse. Finally, additional studies are required to identify the most optimal intervention programs for improving children’s literacy regarding safe internet use.",
"appendix": "Data availability\n\nThe data in this study is qualitative and contains sensitive information. During the data collection process, we assured respondents that their information would not be openly disclosed and that we would only share this data for research purposes. Accordingly, access to these data can be granted upon request to the corresponding author, Professor Md Atiqul Haque, at <atiqulm26@bsmmu.edu.bd>. The data will be provided upon reasonable request, specifically for social science academics and researchers, to further the betterment of society.\n\nMendeley data and DANS Data: These files contain the qualitative semi-structured guideline, https://easy.dans.knaw.nl/ui/datasets/id/easy-dataset:321437 (Islam, 2023) used for conducting in-depth interviews and key informant interviews to explore online child sexual abuse in Bangladesh. The original study was a mixed-method study. This file also contains the “Consolidated criteria for reporting qualitative studies (COREQ)” and the “SAGER guidelines for Sex and Gender Equity in research” for this study, https://data.mendeley.com/datasets/8y7s8wwkcy/1 (Salwa and Haque, 2023).\n\n\nAcknowledgments\n\nAuthors acknowledged all participants for their precious time and insight.\n\n\nReferences\n\nAgatston PW, Kowalski R, Limber S: Students’ perspectives on cyberbullying. J. Adolesc. Health. 2007; 41(6): S59–S60. Publisher Full Text\n\nAin o Salish Kendra: Magnitude and Pattern of Online Child Sexual Abuse in Bangladesh.2023. Accessed February 18, 2023. Reference Source\n\nArfini S, Botta Parandera L, Gazzaniga C, et al.: Online Identity Crisis Identity Issues in Online Communities. Mind. Mach. 2021; 31(1): 193–212. Publisher Full Text\n\nBaumgartner SE, Valkenburg PM, Peter J: Unwanted online sexual solicitation and risky sexual online behavior across the lifespan. J. Appl. Dev. Psychol. 2010; 31(6): 439–447. Publisher Full Text\n\nBaxter A: How Pornography Harms Children: The Advoca’e’s Role. American Bar Association; 2014; 3(5). Reference Source\n\nBento G, Dias G: The importance of outdoor play for young children’s healthy development. Porto Biomed. J. 2017; 2(5): 157–160. Publisher Full Text\n\nÇetin B, Yaman E, Peker A: Cyber victim and bullying scale: A study of validity and reliability. Comput. Educ. 2011; 57(4): 2261–2271. Publisher Full Text\n\nChahal H, Fung C, Kuhle S, et al.: Availability and night-time use of electronic entertainment and communication devices are associated with short sleep duration and obesity among Canadian children. Pediatr. Obes. 2013; 8(1): 42–51. PubMed Abstract | Publisher Full Text\n\nCook CR, Williams KR, Guerra NG, et al.: Cyberbullying: What it is and what we can do about it. NASP Communiqué. 2007; 36(1): 4–5.\n\nCouncil of Europe: No space for violence against women and girls in the digital world.2022. Accessed November 8, 2022. 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Publisher Full Text\n\nJohnstone R: Religion in Society: A Sociology of Religion. 8th ed.Routledge; 2015. Reference Source\n\nKalpogianni DE: Why are the children not outdoors? Factors supporting and hindering outdoor play in Greek public day-care centres. Int. J. Play. 2019; 8(2): 155–173. Publisher Full Text\n\nKeeley B, Little C: The State of the World’s Children 2017: Children in a Digital World.2017. Accessed April 11, 2022. Reference Source\n\nKopecký K, Szotkowski R: Sexting in the population of children and its risks: A quantitative study. Int. J. Cyber Criminol. 2018; 12(2): 376–391. Publisher Full Text\n\nKemp S: Digital 2022: Global Overview Report.2022a. Accessed June 18, 2022. Reference Source\n\nKemp S: Digital 2022: Bangladesh.2022b. Accessed June 18, 2022. Reference Source\n\nKhondkar L: Protecting children online and in the real world.2021. Accessed April 17, 2022. Reference Source\n\nKrug EG, Mercy JA, Dahlberg LL, et al.: The world report on violence and health. Lancet. 2002; 360(9339): 1083–1088. Publisher Full Text\n\nLovejoy B: 40%+ of children under 13 using TikTok, Facebook, and more; high rates of online sexual abuse.2021. Accessed March 14, 2022. Reference Source\n\nMadden AD, Ford NJ, Miller D, et al.: Children’s use of the internet for information-seeking: What strategies do they use, and what factors affect their performance? J. Doc. 2006; 62(6): 744–761. Publisher Full Text\n\nMishna F, Bogo M, Root J, et al.: Here to stay: Cyber communication as a complement in social work practice. Fam. Soc. 2014; 95(3): 179–186. Publisher Full Text\n\nMubassara L, Towhid MII, Sultana S, et al.: Cyber child abuse in Bangladesh: A rural population-based study. World J. Soc. Sci. 2021; 8(1): 104. Publisher Full Text\n\nNabi MS: Unicef: 32% kids at risk of cyberbullying in Bangladesh’.2019. Accessed July 15, 2022. Reference Source\n\nNCTSN: Coping with the Shock of Intrafamilial Sexual Abuse Information for Parents and Caregivers.2009. 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PubMed Abstract | Publisher Full Text\n\nPatchin JW, Hinduja S: Bullies move beyond the schoolyard: A preliminary look at cyberbullying. Youth Violence Juv. J. 2006; 4(2): 148–169. Publisher Full Text\n\nPsychCentral: Why Abuse Survivors Stay Silent.2022. Accessed November 14, 2022. Reference Source\n\nRadford L, Allnock D, Hynes P: Promising Programmes to Prevent and Respond to Child Sexual Abuse and Exploitation. United Nations Children’s Fund. 2015; 1: 1–81.\n\nSalwa M, Haque MA: Online Child Sexual Abuse Qualitative Exploration. Mendeley Data. 2023; V1. Publisher Full Text\n\nSaprea: 11 Factors That Increase the Risk of Child Sexual Abuse.2022. Accessed December 7, 2022. Reference Source\n\nSethi D, Ghatak S: Mitigating cyber sexual harassment: An Insight from India. Asian Themes Soc. Sci. Res. 2018; 1(2): 34–43. Publisher Full Text\n\nShamim I: Child Sexual Abuse and Exploitation Online in Bangladesh: The Challenges of the Internet and Law and Legal Developments. Crime, Criminal Justice, and the Evolving Science of Criminology in South Asia. 2017; 145–171. Publisher Full Text\n\nSoniya R: Social Media for Teaching and Learning. Int. J. Sci. Technol. Humanit. 2017; 3(1 & 2): 363–368. Reference Source\n\nStudySmarter: Conformity to Social Roles: Explanation, Benefits & Behaviour.2022. Accessed December 12, 2022. Reference Source\n\nThe Daily Star: Parents should not impose anything forcefully on children: HC.2022. Reference Source\n\nTuli MP: Bottling the genie of pedophilia.2017. Accessed April 13, 2022. Reference Source\n\nUNICEF: First Digital Children’s Guide to Online Safety in Serbia.2019. Accessed March 14, 2022. Reference Source\n\nUNICEF: Protecting children online.2022. Accessed December 23, 2022. Reference Source\n\nUNODC; Online Child Sexual Exploitation and Abuse.2020. Accessed December 25, 2022. Reference Source\n\nVan Ouytsel J, Van Gool E, Walrave M, et al.: Sexting: Adolescents’ perceptions of the applications used for, motives for, and consequences of sexting. J. Youth Stud. 2017; 20(4): 446–470.\n\nWard T, Siegert RJ: Toward a comprehensive theory of child sexual abuse: A theory knitting perspective. Psychol. Crime Law. 2002; 8(4): 319–351. Publisher Full Text\n\nWarren J: BANGLADESH Policy Progress to End Violence against Children. World Vision; 2019. Reference Source\n\nWHO: Violence against children.2022. Accessed December 26, 2022. Reference Source\n\nWorldometers: Bangladesh Population.2023. Accessed January 07, 2023. Reference Source\n\nWright L: Parents Blame Child Sex Abuse Victims More if Perpetrator is Another Youth, UNH Research Shows. UNH Today. 2012; 2012: 3885. Reference Source\n\nYLE: Suspected pedophile uses volunteer programme as cover for child sex abuse.2018. Accessed March 11, 2022. Reference Source"
}
|
[
{
"id": "216676",
"date": "29 Nov 2023",
"name": "Salim Mahmud Chowdhury",
"expertise": [
"Reviewer Expertise Health system research and injury 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\nLanguage editing is needed. Conclusion section of the abstract has study findings (better to focus on policy implication of the study). Rural urban population distribution mentioned in the introduction section needs to be reviewed. Operational definition of youth is needed. Please check the strength and limitations of study section to avoid repetition of same information. Conclusion section should be more structured to make this paper reader-friendly.\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?\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": [
{
"c_id": "10883",
"date": "16 Jan 2024",
"name": "Md Redwanul Islam",
"role": "Author Response",
"response": "Thank you for your suggestion. We agreed with your feedback and addressed all the comments in the manuscript with changes marked. We have enhanced the language throughout the manuscript. The conclusion section of the abstract has incorporated the policy implications of the study. In the introduction section, we have revised the distribution of the rural-urban population. We agreed with the reviewer and provided an operational definition for youth. The strengths and limitations section has been reviewed to avoid repetition of information. The conclusion section has been modified to make it reader-friendly."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1364
|
https://f1000research.com/articles/12-514/v1
|
18 May 23
|
{
"type": "Study Protocol",
"title": "Comparative evaluation of the effect of 2% graphene oxide and 5% hydroxyapatite nanoparticles in isolation and in combination on micro tensile bond strength of 5th generation adhesive",
"authors": [
"Simran Kriplani",
"Shweta Sedani"
],
"abstract": "Graphene is the thinnest, strongest and stiffest imaginable material. The biocompatible property of graphene oxide can initiate and facilitate cell adhesion, proliferation and differentiation of periodontal ligament, osteogenic and oral epithelial cells. Furthermore, the antibiofilm and anti-adhesion properties of graphene oxide in prevention of dental biofilm infections, dental caries, dental erosion as well as for implant surface modification and as anti-quorum sensing agent. Composites are most often utilised materials for restoration in the field of dentistry due to adhesive resins' improved mechanical and cosmetic properties. To safeguard the dentin and prevent dental cavities, dentin adhesives are utilised to affix hydrophobic resin composites to hydrophilic dentin tissue. Dental adhesives have a harder time adhering to dentin because it contains more water and is less mineralized than enamel. This makes the method more sensitive. As a result, it was chosen to assess and contrast the impact of 5% Hydroxyapatite nanoparticles and 2% Graphene oxide nanoparticles, both separately and together, on the Micro tensile bond strength of 5th generation adhesive. Graphene oxide is the most versatile form of Graphite in structural and functional configuration. Graphene oxide possess extraordinary physical, chemical, optical, electrical and mechanical properties. Among the graphene family nanomaterials, the reduced form of Graphite adding the oxygenated functional group to the structure increases the surface area and therefore exhibits enviable excellent interaction ability with metal and ions as well as organic species. Graphene oxide in dentistry has provided outstanding results in antimicrobial action, regenerative dentistry, bone tissue engineering, drug delivery, physicochemical property, enhancement of dental biomaterials and oral cancer treatment.",
"keywords": [
"Nanocrystals",
"Dental adhesive",
"Graphene oxide",
"Hydroxyapatite",
"Anti-microbial",
"Biocompatibility",
"Hydrophobic",
"Micro-tensile bond strength."
],
"content": "Introduction\n\nConsidering their enhanced aesthetics and increased mechanical qualities, the most used materials for restoration in dentistry is dental composite.1 Dentin adhesives are utilized to treat and prevent dental caries as well as to adhere hydrophobic resin composites to hydrophilic dentin tissue.2 Dental adhesives have a harder time adhering to dentin because it contains more water and is less mineralized than enamel. This necessitates meticulous handling as it is highly sensitive to the procedures being performed3 Effectiveness of adherence with dentin in tooth structure is related to the monomers' capacity to extend and enter the gaps between collagen fibers and the stability of the resin-based tags used to create a hybrid layer.4 Loss of adhesive bond over time is considered one of the prime causes of composite restorative failure leading to complications.5 Bond failure as well as the emergence leading to secondary caries are caused by loss of bond, which results in causing the production of nano-gaps.6 To boost dentin interactions with adhesive resins also maybe lessen dentin-adhesive degradation to counteract failure of adhesion over time, also use of inorganic fillers to adhesives is advised.7 Recent research has demonstrated that addition of fillers in adhesives can improve their mechanical qualities while reducing water sorption and solubility.8,9 Thus, it is extremely desirable to incorporate inorganic nanomaterials as fillers/particles to enhance the physicomechanical characteristics of bonding agents. In recent years, dental researchers have become interested in several materials, including graphene. Materials made of graphene have a large surface area therefore both are thermally and chemically stable.10 Graphene oxide (GO), a member of the graphene family of nanomaterials, is particularly interesting and is produced by oxidizing graphite.11 Graphene is typically thought of as a hydrophobic material, however, because GO has oxygen in its functional groups compared to other GFNs (graphene family nano particles) it is thought to be hydrophilic.12 Its hydrophilicity could be viewed as a positive trait because it aids in the formation of stable colloid dispersion so prevents aggregation, making GO more cytocompatible.13 Lee et al. incorporated GO into dentin adhesive successfully in 2018 despite using a mix of GO and bioactive glass since it has better antibacterial activity than graphite does.14 Also, the combination of GO with the remineralizing substance hydroxyapatite (HA) will be tested in this study to see how it affects the adhesive's characteristics. HA is an inorganic, non-toxic bioactive substance that is frequently found as a significant component of tooth structure and is available as nanoparticles.15 Due to HA's demonstrated ability to remineralize bone, the number of dental materials that include it has increased.16 Due to the dental adhesives' intimate contact with tooth dentin, incorporation of HA nanoparticles in resin adhesives aids in remineralizing the caries-affected dentin. Moreover, the hybrid dentin layer's interaction with HA to create an organic bond will make it more difficult for it to separate from the tooth.17 In a study performed earlier, Leitune et al. (2013) found that incorporating nanoparticles of HA in the dental adhesive increased the binding strength between the adhesive and the dentin.18 In a study performed earlier by Bin-Shuwaish et al. (2010) showed how GO particles might enhance the mechanical properties of glue.19 In a related earlier study, Mei et al. in 2017 found that the addition of 1 wt % GO-silica particles might enhance compressive strength of the adhesives.20 Also, our study compares the impact of 5% Hydroxyapatite nanoparticles and 2% Graphene oxide nanoparticles, onto micro tensile bond strength when used alone and together. It is anticipated that more GO particles will be added to enhance the experimental dentin's binding capacity, durability, and dentin interaction. The conventional dental adhesive systems clinically being used in dentistry and their physical and mechanical properties varied widely in terms of bond strength and adhesion at the dentin interface which further compromised the prognosis leading to failure of the treatment. To improvise the related required properties in the 5th generation adhesive system, the graphene oxide and hydroxyapatite nanoparticles will be incorporated considering their promising structural configuration additive physical and mechanical properties aiding in the enhancement of the dental material. The focus of our study is to evaluate increase in the Micro tensile Bond strength of the 5th Generation Adhesive system after the incorporation of the graphene oxide and hydroxyapatite nanoparticles. Adhesion of the nanoparticles at the dentin interface leading to widespread surface area may further contribute to the increased bond strength, enhancing the mechanical properties.\n\n\nDiscussion\n\nBefore materials are marketed in dentistry, it is crucial to conduct and analyze mechanical strength tests on them. Through laboratory investigations, these evaluations are carried out in a variety of ways. Using the TBS test method, the bonding strengths of self-adhesive composite resins with various universal bonding methods were examined in this study. The TBS values increased when the adhesive system was used with universal adhesive systems. As a result, our study's null hypothesis was rejected. The fifth-generation resin adhesive's bond integrity, longevity, and contact with dentin were studied in the current study in relation to the addition of nano-HA and different nano-GO particle concentrations (0.5 wt% and 2 wt%). The Hydroxyapatite-graphene oxide nanoparticles 2% group demonstrated greater micro tensile bond strength than the Hydroxyapatite-graphene oxide nanoparticles 0.5% group, which revealed greater than the controls, according to the data. The idea that adding graphene oxide nanoparticles to the bonding agent would strengthen its binding was therefore considered. Adhesives are essential for the clinical outcome of restorations because inadequate restorative adhesive bonds have been linked to secondary caries development, dentin hypersensitivity (DH), and microleakage.21 Dental composites' diverse mechanical and physical qualities are reinforced by the universal use of nanoparticles.22 The nano-HA particles have a great ability to connect with the dental tissues, are biocompatible, and serve as a source of remineralizing ions like Ca and P.23,24 According to the current study, adding nano-HA particles to the adhesive produces all the advantages of using HA in adhesives. Nano-HA particles have been proposed in the past as a way to improve mechanical characteristics of adhesive and enhance surface area for adhesion.25 This recommendation was carried out, and nano-HA particles were used in the current study (100 nm in size). Nano-GO particles were added to HA-containing glue at two different concentrations (0.5% and 2.0%) to further enhance the adhesive bonding properties of the experimental adhesives. The inclusion of foreign fillers in the glue must be evenly distributed to reap the full benefits. The optimal performance of the adhesive may be compromised by gaps or cracks created by an incomplete or partial diffusion of filler nanoparticles.26 Microorganisms can live in the dental plaque and produce pulpal irritation and dental cavities. According to a prior study by Cantore et al., in which an alcohol-free mouthwash shows comparable antibacterial effectiveness to regular antimicrobial mouthwash chlorhexidine and can also reduce the risk of plaque formation. Dental caries and pulpal inflammation are prevented by every component of an oral product that is antibacterial and can lower microbial burden.27 Key dental pathogens like Streptococcus mutans are not able to adhere to graphene-based dental adhesives.\n\n\n\n1. To evaluate the micro tensile bond strength of the 5th generation bonding agent without incorporating any of the nanoparticles using a universal testing machine.\n\n2. To evaluate the micro tensile bond strength of a 5th generation bonding agent incorporating 2% Graphene oxide nanoparticles in isolation using a universal testing machine.\n\n3. To evaluate the micro tensile bond strength of 5th generation bonding agent incorporating 5% Hydroxy apatite nanoparticles in isolation using a universal testing machine.\n\n4. To compare the micro tensile bond strength of 5th generation bonding agent incorporating 2% graphene oxide and 5% Hydroxyapatite nanoparticles in combination using a universal testing machine.\n\nTRIAL DESIGN: In-vitro study\n\nProtocol\n\nMaterials required:\n\n1. Graphene oxide nanoparticles (Nano Research Lab, Jamshedpur, India)\n\n2. Hydroxyapatite nanoparticles (Nano Research Lab, Jamshedpur, India)\n\n3. 5th generation bonding agent (3M ESPE Adper Single Bond 2)\n\n4. Dentsplyspectrum - composite restoration\n\n\n\n▸ Inclusion criteria\n\n• 84 Maxillary premolars\n\n• Teeth devoid of restorations\n\n▸ Exclusion criteria\n\n• Teeth with previous root canal treatment.\n\n• Extensively carious tooth.\n\n• Abrasion, attrition, fluorosis, or other enamel defects.\n\n• Teeth with developmental anomalies.\n\n• Teeth with external and internal resorption.\n\n\n\n➢ A total of 84 samples are used in the study divided into 4 groups, 21 in each group corresponding to the 1, 2, 3, and 4 sample sets.\n\n➢ Group 1 – 5th generation bonding agent\n\n➢ Group 2-5th generation bonding agent with graphene oxide nanoparticles.\n\n➢ Group 3-5th generation bonding agent with hydroxy apatite nanoparticles\n\n➢ Group 4-5th generation bonding agent with a combination of graphene oxide and hydroxy apatite nanoparticles.\n\nProcedure:\n\n1. Addition of HA to the dentin Adhesive\n\nThe nano-HA particles will be silanized after being purchased commercially. 5% silane will be added to the 95% adhesive to help the nano-hydroxyapatite stick to it.\n\nSolvent for silanization using acetone. To create a fifth adhesive system that contains 5 wt% nano-Hydroxyapatite particles, the nano-HA particles will be introduced to the experimental adhesive at a 5% concentration (m/m). The experimental adhesive's nano-hydroxyapatite particles will be dispersed using sonication in a centrifuge to encourage homogenization. To allow the solvent to evaporate, the synthesized adhesives will be stored in isolation for 24 hours at 37 degrees oC. Due to their short shelf life, the adhesives will thereafter be stored at 4 degrees oC and used for the duration of 20 days after formulation.\n\n1. Adding Graphene oxide to the dentin Adhesive\n\nThe graphene oxide powder will be combined with 2 mL of ethanol in a microbial and ultrasonically processed for 10 minutes at room temperature. The dentin adhesive will get this mixture. The nano-graphene oxide particles will first be combined with resin before being sonicated in an ultrasonic bath for 10 minutes so creating a uniform combination. After sonication, the mixture will be homogenized for 60 seconds at room temperature in an ultrasonic homogenizer using pulse on/off technology. Every time the mixture is used, the mix will be homogenized in an ultrasonic homogenizer to ensure that the graphene oxide will disperse uniformly after storage. Calculations will be done to determine the resin volume in milliliters and milligram weight of nanoparticles. Using the following:\n\n2. Addition of GO and HA to the dentin Adhesive\n\nThe graphene oxide powder will be combined with 2 mL of ethanol in a microbiological container before being ultrasonically processed for 10 minutes at room temperature. The nano-HA particles were silanized after being purchased commercially. The 95% acetone solvent will receive an addition of 5% silane for silanization to enhance the adherence of nano-Hydroxyapatite to the adhesive. Once both the nanoparticles are made, the made solvents will be added to the 5th generation dentin adhesive. To achieve a homogenous mixture, it will be sonicated in an ultrasonicator duration of 10 min. Post-sonication, mixture will be homogenized in ultrasonic homogenizer at pulse on/of for 60 s at room temperature. The mixture will be rehomogenized in the ultrasonic homogenizer before each and every use to ensure that graphene oxide and hydroxy apatite nanoparticles would disperse uniformly after storage. Calculations will be done to determine the resin volume in millilitres and milligrams weight of the nanoparticles. This will allow the solvent to evaporate, the synthesized adhesives will be stored in isolation for 24 hours at 37 degrees oC. Due to their short shelf life, the adhesives will thereafter be stored at 4 degrees oC and will be used within 20 days of the formulation.\n\nThe investigation will use extracted permanent maxillary premolars. All teeth will be kept in the storage media for a maximum of three months in distilled water. The 1, 2, 3, and 4 sample sets will be represented by the groups of the 84 premolars, which will be randomly divided into those groups. There will be Class 1 cavity preparation. The 3 M Scotchbond Universal Etchant (30 – 40% phosphoric acid) will be applied to all groups for 15 seconds. The surfaces will then be washed and dried by air. The surplus glue will then be removed using dental cotton rolls after adhesive systems have been placed for 15 seconds. The surfaces will then be exposed to light for nearly 20 seconds at an intensity of around 800 mW/cm2 using a light-curing device. The previously polymerized adhesive layer will be covered with successive 2-mm thick layers using Dentsply Spectrum -restorative material, which will then be light cured for 20 seconds. Following treatment, all of the teeth will be further separated into resin dentin sticks using a diamond discs and water cooling in accordance with ISO/TS 11405, with an average cross-sectional area of 1 mm by 1 mm. The samples will then be kept in deionized (DI) water for 24 hours at 37 °C. Next, utilizing universal testing machine, the created samples will go through a micro-tensile bond strength test. The beams will be secured to a jig with cyanoacrylate adhesive before being put to tensile stresses at a crosshead speed of one millimeter per minute.\n\nPrimary Variable - Microtensile bond strength\n\nSample size formula for difference between two means:\n\nWhere;\n\nZα = level of significance at 5% i.e., 95%\n\nConfidence interval = 1.96\n\nZβ is the power of test =80% =0.84\n\nδ1 =SD of MTBS in group 1 =29.74 ± 3.81\n\nδ2 = SD of MTBS in group 2 =25.21 ± 3.60\n\n∆ = Difference between two means\n\n=4.53\n\nPooled std. dev.= (3.81+3.60)/2 =3.71\n\nn =15 teeth needed in each group\n\nTotal sample size is 60\n\nStudy Reference: [28]\n\nSTATISTICAL METHOD: All the results will be calculated using SPSS version 27 software, a proprietary alternative in which the analysis can be carried out is R Studio. Data for outcomes variables will be tested for normality using kalmogorov-smirnov. The comparative analysis of the micro tensile bond strength will be evaluated on the measurement of Newton. ANOVA will be used to find the significant difference between the mean of the 4 groups. Tukey test will be used for comparative evaluation of measurement in between 2 groups pairwise. P- value ≤ 0.05 will be considered as significant at 5% level of significance and 95% confidence of interval.\n\n\nConclusions\n\nIt is expected that among the material used in the study, the 5th generation bonding agent with graphene oxide and nano hydroxyapatite crystals in combination may give better results as compared to the 5th generation bonding agent with or without incorporation of graphene oxide and nano hydroxyapatite crystals in isolation in routine practice due to its ability of anti-microbial properties, optimal biocompatibility, and increased bond strength.\n\nThe focus of our study is to evaluate increase in the micro tensile bond strength of the 5th generation adhesive system after the incorporation of the graphene oxide and hydroxyapatite nanoparticles. Adhesion of the nanoparticles at the dentin interface leading to widespread surface area may further contribute to the increased bond strength, enhancing the mechanical properties.\n\nNot started yet.\n\nEthical approval received from Datta Meghe Institute of Higher Education and Research, Sawangi, Wardha\n\nIEC reference number- DMIHER (DU)/IEC/2023/584",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nI would like to thank my institute, my Guide, HOD and my colleagues.\n\n\nReferences\n\nBregnocchi A, Zanni E, Uccelletti D, et al.: Graphene-based dental adhesive with anti-biofilm activity. J. Nanobiotechnol. 2017; 15: 89. [CrossRef]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDe Almeida Neves A, Coutinho E, Cardoso MV, et al.: Current concepts and techniques for caries excavation and adhesion to residual dentin. J. Adhes. Dent. 2011; 13: 7–22. [PubMed]. PubMed Abstract | Publisher Full Text\n\nAl-Hamdan RS, Almutairi B, Kattan HF, et al.: Assessment of Hydroxyapatite Nanospheres Incorporated Dentin Adhesive. An SEM/EDX, Micro-Raman, microtensile, and Micro-Indentation Study. Coatings. 2020; 10: 1181. [CrossRef]. Publisher Full Text\n\nHuang B, Siqueira WL, Cvitkovitch DG, et al.: Esterase from a cariogenic bacterium hydrolyzes dental resins. Acta Biomater. 2018; 71: 330–338. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBreschi L, Maravic T, Cunha SR, et al.: Dentin bonding systems: From dentin collagen structure to bond preservation and clinical applications. Dent. Mater. 2018; 34: 78–96. [CrossRef]. PubMed Abstract | Publisher Full Text\n\nFerracane JL: Models of Caries Formation around Dental Composite Restorations. J. Dent. Res. 2017; 96: 364–371. [CrossRef]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBin-Shuwaish MS, Maawadh AM, Alhamdan RS, et al.: Influence of graphene oxide filler content on the dentin bond integrity, degree of conversion and bond strength of the experimental adhesive. An SEM, micro-Raman, FTIR, and microtensile study. Mater. Res. Express. 2020; 7: 11. [CrossRef]. Publisher Full Text\n\nKalachandra S: Influence of fillers on the water sorption of composites. Dent. Mater. 1989; 5: 283–288. [CrossRef]. Publisher Full Text\n\nAlshahrani A, Bin-Shuwaish MS, Al-Hamdan RS, et al.: Graphene oxide nano-filler based experimental dentine adhesive. An SEM/EDX, Micro-Raman, and micro tensile bond strength analysis. J. Appl. Biomater. Fundam. Mater. 2020. [CrossRef]\n\nBaig MS, Fleming GJ: Conventional glass-ionomer materials: A review of the developments in glass powder, polyacid liquid and the strategies of reinforcement. J. Dent. 2015; 43: 897–912. [CrossRef]. PubMed Abstract | Publisher Full Text\n\nGe Z, Yang L, Xiao F, et al.: Graphene Family Nanomaterials: Properties and Potential Applications in Dentistry. Int. J. Biomater. 2018; 2018: 1539678. [CrossRef] [PubMed].\n\nWei N, Lv C, Xu Z: Wetting of graphene oxide: A molecular dynamics study. Langmuir. 2014; 30: 3572–3578. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text\n\nSeabra AB, Paula AJ, de Lima R , et al.: Nanotoxicity of graphene and graphene oxide. Chem. Res. Toxicol. 2014; 27: 159–168. [CrossRef] [PubMed]. Publisher Full Text\n\nLee S-M, Yoo K-H, Yoon S-Y, et al.: Enamel Anti-Demineralization Effect of Orthodontic Adhesive Containing Bioactive Glass and Graphene Oxide: An In-Vitro Study. Materials. 2018; 11: 1728. [CrossRef]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFarooq I, Moheet IA, AlShwaimi E: In vitro dentin tubule occlusion and remineralization competence of various kinds of toothpaste. Arch. Oral Biol. 2015; 60: 1246–1253. [CrossRef]. PubMed Abstract | Publisher Full Text\n\nPhilip N: State of the Art Enamel Remineralization Systems: The Next Frontier in Caries Management. Caries Res. 2019; 53: 284–295. [CrossRef]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKavrik F, Kucukyilmaz E: The effect of different ratios of nano-sized hydroxyapatite fillers on the micro-tensile bond strength of an adhesive resin. Microsc. Res. Tech. 2019; 82: 538–543. [CrossRef]. PubMed Abstract | Publisher Full Text\n\nLeitune VC, Collares FM, Trommer RM, et al.: The addition of nanostructured hydroxyapatite to an experimental adhesive resin. J. Dent. 2013; 41: 321–327. [CrossRef]. PubMed Abstract | Publisher Full Text\n\nQian W, Hu X, He W, et al.: Polydimethylsiloxane incorporated with reduced graphene oxide (rGO) sheets for wound dressing application: Preparation and characterization. Colloids Surf. B. Biointerfaces. 2018; 166: 61–71. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text\n\nMei L, Wei H, Wenjing C, et al.: Graphene Oxide-Silica Composite Fillers into the Experimental Dental Adhesives for Potential Therapy. Med. Res. 2017; 1: 42. [CrossRef]. Publisher Full Text\n\nCarvalho RM, Manso AP, Geraldeli S, et al.: Durability of bonds and clinical success of adhesive restorations. Dent. Mater. 2012; 28: 72–86. [CrossRef]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSolhi L, Atai M, Nodehi A, et al.: A novel dentin bonding system containing poly (methacrylic acid) grafted nanoclay: Synthesis, characterization and properties. Dent. Mater. 2012; 28: 1041–1050. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text\n\nNobre CMG, Putz N, Hannig M: Adhesion of Hydroxyapatite Nanoparticles to Dental Materials under oral Conditions. Scanning. 2020; 2020: 6065739. [CrossRef] [PubMed].\n\nPepla E, Besharat LK, Palaia G, et al.: Nano-hydroxyapatite and its applications in preventive, restorative and regenerative dentistry: A review of the literature. Ann. Stomatol. 2014; 5: 108–114. [CrossRef]. PubMed Abstract\n\nMelo MA, Cheng L, Zhang K, et al.: Novel dental adhesives containing nanoparticles of silver and amorphous calcium phosphate. Dent. Mater. 2013; 29: 199–210. [CrossRef]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMortazavi V, Fathi M, Ataei E, et al.: Shear bond strengths and morphological evaluation of filled and unfilled adhesive interfaces to enamel and dentine. Int. J. Dent. 2012; 2012: 858459. [CrossRef].\n\nCantore S, Ballini A, Mori G, et al.: Anti-plaque and antimicrobial efficiency of different oral rinses in a 3-day plaque accumulation model. J. Biol. Regul. Homeost. Agents. 2016; 30: 1173–1178. PubMed Abstract\n\nAlFawaz YF: Dentin Bond Integrity of Hydroxyapatite Containing Resin Adhesive Enhanced with Graphene Oxide Nano-Particles—An SEM, EDX, Micro-Raman, and Microtensile Bond Strength Study.2020"
}
|
[
{
"id": "204068",
"date": "14 Nov 2023",
"name": "Ranj Nadhim Salaie",
"expertise": [
"Reviewer Expertise Dental Implantology",
"Nano coatings",
"Nano Dentistry",
"Dental Biomaterials",
"Antibacterial Biomaterials",
"Oral 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\n1- Proof reading is required, inappropriate use of grammar, punctuation in some sentences\n2- Where are the micro tensile bond strength data? there must be some graphs from the universal tensile machine software.\n\n3- I appreciate that this is a method development study. However, since the authors have conducted statistics, I expect the data and the stats available in the main text. I cant find them anywhere! any explanation please ?\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? Partly",
"responses": [
{
"c_id": "10643",
"date": "27 Nov 2023",
"name": "Simran Kriplani",
"role": "Author Response",
"response": "Proofreading is required, inappropriate use of grammar, and punctuation in some sentences Answer for the first query - The grammar correction and the proofreading have been done. According to the Grammarly app, the version 2 has more than 95% accuracy. Where are the micro tensile bond strength data? there must be some graphs from the universal tensile machine software. Answer for the second query- This is the protocol and the method of testing microtensile bond strength designed for the study to be conducted further and so the data and graphs related to same will be posted once the study is performed according to this protocol adopted. I appreciate that this is a method development study. However, since the authors have conducted statistics, I expect the data and the stats available in the main text. I can't find them anywhere! any explanation, please? Answer for the third query- As this is a research protocol the statistics mentioned here are for sample size calculation which will be used further for original research, the details of which will be published in the original article. Thank you for your valuable response. Proofreading is required, inappropriate use of grammar, and punctuation in some sentences Answer for the first query - The grammar correction and the proofreading have been done. According to the Grammarly app, the version 2 has more than 95% accuracy. Where are the micro tensile bond strength data? there must be some graphs from the universal tensile machine software. Answer for the second query- This is the protocol and the method of testing microtensile bond strength designed for the study to be conducted further and so the data and graphs related to same will be posted once the study is performed according to this protocol adopted. I appreciate that this is a method development study. However, since the authors have conducted statistics, I expect the data and the stats available in the main text. I can't find them anywhere! any explanation, please? Answer for the third query- As this is a research protocol the statistics mentioned here are for sample size calculation which will be used further for original research, the details of which will be published in the original article. Thank you for your valuable response."
},
{
"c_id": "10931",
"date": "14 Jun 2024",
"name": "Ranj Nadhim Salaie",
"role": "Reviewer Response",
"response": "Accepted"
}
]
}
] | 1
|
https://f1000research.com/articles/12-514
|
https://f1000research.com/articles/12-1425/v1
|
31 Oct 23
|
{
"type": "Research Article",
"title": "A Comparison of Pain Before and After Transfusion in Adult transfusion-dependent thalassemia (TDT) Using BPI-SF",
"authors": [
"Uni Gamayani",
"Shenny Dianathasari Santoso",
"Asep Nugraha Hermawan",
"Pandji Irani Fianza",
"Ramdan Panigoro",
"Shenny Dianathasari Santoso",
"Asep Nugraha Hermawan",
"Pandji Irani Fianza",
"Ramdan Panigoro"
],
"abstract": "Background\n\nPain is a complication in patients with transfusion-dependent thalassemia (TDT). There are several mechanisms underlying pain in people with thalassemia and low hemoglobin at the end of the transfusion cycle was the most etiology. Pain can develop into chronic pain and interfere with the quality of life. The Brief Pain Inventory Short Form (BPI-SF) can help identify pain in people with TDT. The present study aimed to compare pain before and after transfusion in adult TDT patients.\nMethods\nIt was an analytical observational study using a cross-sectional design on adult TDT patients with pain who came to the Haemato-Oncology Clinic of Dr. Hasan Sadikin Hospital Bandung. This study was conducted from December 2020 to July 2021. All subjects were assisted in filling out the Indonesian version of the BPI-SF questionnaire hemoglobin levels were examined and before and after transfusion, then paired test analysis was performed using the Wilcoxon Test.\nResults\nThis study is conducted on 60 adult TDT patients with symptoms of pain. The median value of pain intensity and pain interferes with life obtained from the Indonesian version of the BPI-SF score after transfusion decreased significantly compared to before transfusion (NRS 5 vs. 0 and 2.8 vs. 0; p=0.0001).\nConclusion\nThere is a significant difference in pain intensity and pain interfere with life in adults with TDT before and after transfusion. It is necessary to carry out pain assessments for thalassemia patients.",
"keywords": [
"Thalassemia",
"hemoglobin",
"pain",
"transfusion",
"BPI-SF",
"quality of life",
"questionnaire",
"pain assessment",
"adults."
],
"content": "Introduction\n\nPain is an unpleasant sensory and emotional experience for everyone but is not as a chief complaint and ignored in daily examinations. Recent studies have shown increasing pain reports in patients with thalassemia.1,2 Thalassemia is the blood disorder occuring due to decreased or lost synthesis of one or more globin chains.3 This disease is hereditary autosomal recessive due to mutations in the globin-forming gene.4,5 The spectrum of thalassemia syndromes is based on the requirements for blood transfusions for survival, including transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT).6\n\nThe World Health Organization or WHO states that about 7% of the world's population has the thalassemia gene, the highest incidence of up to 40% cases in Asia. β-thalassemia is found in Mediterranean countries, Central Asia, India, Southern China, North Africa and South America. Indonesia is included in the world's thalassemia belt area with the carriers incidence of thalassemia traits ranging from 6-10%.7 There were more than 10.531 thalassemia patients in Indonesia according to the data from the Ministry of Health of the Republic of Indonesia in 2019. Dr. Hasan Sadikin Hospital Bandung is a referral hospital for West Java Province with the highest thalassemia cases in Indonesia reaching 40 percent of the national figure.8\n\nThere are several mechanisms underlying pain in people with thalassemia. Low hemoglobin at the end of the transfusion cycle can cause pain in 45% cases and decrease after transfusion.9 Low hemoglobin in thalassemia causes hypoxia and releases reactive oxygen species (ROS) through inhibition activity of oxygen-sensitive prolyl hydroxylases (PHDs), then causes activation of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1).10,11 This protein activation will release substance P which plays a role in pain sensitization.12 Transfusion can improve anemia, suppress erythropoiesis, and inhibit iron absorption in the gastrointestinal tract. Maintaining hemoglobin levels above 10 g/dL can prevent hyperplasia and bone marrow expansion, thereby preventing the development of skeletal abnormalities.4,13\n\nThe pain effect in daily activities needs to be assessed using a pain screening tool. The Brief Pain Inventory (BPI) is the recommended pain screening tool to assess pain intensity and pain interfering with life.14 The advantage of this questionnaire is available in a short form and easier to apply. This questionnaire can evaluate pain treatment and the pain impact on the patient's life quality with the sensitivity of 79.4%.15–18\n\nPain in thalassemia needs to be identified because it can develop into chronic pain which can interfere the patients' life quality. Pain management in thalassemia depends on the pain assessment accuracy. This study aims to compare pain before and after transfusion in adult TDT patients.\n\n\nMethods\n\nThis study inclusion criteria was ≥18-year-old patients diagnosed with β-thalassemia with pain who underwent routine transfusion at the Hemato-Oncology Internal Medicine Clinic in Dr. Hasan Sadikin Hospital Bandung and was willing to participate in the research. Transfusion is initiated if the thalassemia diagnosis is confirmed based on severe anemia (hemoglobin level <7 g/dL for more than two weeks, excluding other anemia causes or hemoglobin level >7 g/dL with a facial deformity, impaired growth, presence of bone marrow expansion, and hepatosplenomegaly). The target for hemoglobin after transfusion is 13-14 g/dL; therefore, the transfusion frequency is every 2-4 weeks to achieve the hemoglobin target. The patient received 1-2 units of blood transfusion depending on the hemoglobin level before transfusion. The procedure was done in 3-4 hours. This adult selection as the subject (It ranges from the age of 18 in our hospital) was done since they were expected to be able to express pain more. Exclusion criteria was patients who had confirmed pain due to fractures/other diseases and had been diagnosed with anemia due to other causes.\n\nThe sample size of this study consists of subjects testing the questionnaire validity and the sample size for paired test analysis. The sample size for questionnaire validation in this study was determined using a correlation analysis formula obtained from 30 subjects. Subjects filling out the questionnaire complained various types of pain such as low back pain, nerve entrapment pain, radiculopathy, joint pain, and facial pain. The minimum sample size for paired test analysis is 46 research subjects. If 10% is added to anticipate data loss, the minimum sample size then is 51 research subjects. A total of 60 TDT patients were obtained according to the period of our research.\n\nThe written informed consent for this research was obtained from the patient and research ethics approval was obtained from the ethics committee of Padjadjaran University Bandung under the ethical clearance number of 198/UN6.KEP/EC/2021.\n\nThis study was an analytical observation using a cross-sectional design conducted from December 2020 to June 2021. We perform the BPI-SF questionnaire validity test in the Indonesian version. The validity test stages were done according to the questionnaire validation guidelines using the following steps as described in Figure 1.19\n\nSixty subjects meeting the inclusion criteria were explained about the study procedure and asked to sign an informed consent form if they were willing to participate; furthermore, demographic data collection and pain screening were carried out on the subject using the BPI-SF questionnaire. Patients were assisted before the transfusion and a maximum of one day after the transfusion in filling out the BPI-SF questionnaire in Indonesian version. The data was obtained by telephone interview due to the COVID-19 pandemic and the distant patient residence from the research site. Hemoglobin levels were examined before and after transfusion, and then a comparison test was performed with the Wilcoxon Test.\n\n\nResults\n\nThe validity test of this study uses Pearson's correlation. The results were obtained and processed using SPSS 24.0 software with a significance level (α)=0.05 (5%). The questionnaire is considered valid if it is greater than the Pearson product-moment correlation coefficient. The table correlation number (r table) is 0.30 with the number of samples (n)=30 people. All question instruments on the questionnaire variable are valid because the r-count is > 0.3. Reliability testing is carried out with internal consistency or the answers accuracy degree using Cronbach's Alpha. A measuring instrument is said to be reliable if the coefficient value of r is 0.7. All questionnaire variable instruments are reliable because of the r > 0.7 value.\n\nThis study was conducted to 60 people with thalassemia meeting the inclusion criteria and not included in the exclusion criteria. The subjects mean age was young adults, 26.1±9.1 years, and most of them were female (65%). The duration of being diagnosed with thalassemia ranged from 3-50 years. The subjects demographic distribution is described in Table 1.\n\nThe pain location is experienced mainly in the lower back followed by the knee while the others complained it in more than one location, as seen in Figure 2.\n\nMost of the subjects have never been examined for their pain, so the cause of pain were not further assssesed. Based on the data of the study, the average pain intensity was moderate pain and disappeared after transfusion. The data can be seen in Figure 3.\n\nQuestions in the BPI-SF questionnaire about the treatment taken by the patient and the pain treatment effect were not included in the scoring assessment. This study showed that the most pain is reduced by transfusion in 20 (30%) patients with an effect of 40–100% pain reduction. Other treatments taken by the subjects are analgetics drugs, rest, compress, and iron chelation. There is an increase in the average hemoglobin before transfusion from 7±1.1 g/dL to 8.9±1.1 g/dL.\n\nPain intensity before transfusion had a median value of 5 while pain intensity after transfusion had a median value of 0. These numerical data were analyzed using the Wilcoxon test. The analysis results showed a significant difference in pain intensity before and after transfusion with p=0.0001 (<0.05). A comparison of pain interfering with life obtained from BPI-SF scores before and after transfusion using the Wilcoxon test obtained p=0.0001 (<0.05); accordingly, there is the significant difference in pain interfering with life before and after transfusion as listed in Table 2.\n\n** p<0.05 was considered significant.\n\n\nDiscussion\n\nMost of the subjects did not disclose their pain to the doctor when they went to the Haemato-Oncology Clinic. There were only two subjects who checked for pain and carried out supporting examinations to determine the pain cause. Forty-nine other subjects were known to have pain based on the results of filling out the BPI-SF questionnaire. Low hemoglobin in thalassemia causes hypoxia and releases reactive oxygen species (ROS) through inhibition activity of oxygen-sensitive prolyl hydroxylases (PHDs), then causes the activation of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1).10,11 This protein activation will release substance P which plays the role in pain sensitization.12\n\nTRPA1, a nonselective cation channel, is widely expressed in nociceptive C fibers, dorsal root ganglia (DRG) and trigeminal ganglia neurons.11 Human nerve fibers are susceptible to free radicals such as ROS since it is high in phospholipids and mitochondria; furthermore, the neurons antioxidant defenses are weak. TRPV1 is a nonselective cation channel expressed mainly in unmyelinated C nerve fibers detecting and integrating pain stimuli. TRPV1 can be sensitized by exposure to hypoxia and can induce pain.10 The role of TRPV1 and TRPA1 in thalassemia-related pain are thought to be associated with arthritis. These two molecules can be activated in sensory neurons, chondrocytes and synoviocytes.20\n\nPain in thalassemia is associated with musculoskeletal involvement with a wide variety of symptoms.21 The most common complaints of musculoskeletal pain are arthritis and low back pain.1,22,23 The musculoskeletal pain primary location is in the lower back affecting 70-85% of the adult population.24 Pain-sensitive structures in the lower back are involved in pain such as the periosteum of the bones, ligaments, facets, articular capsule, and paraspinal muscles.25–27 The lower back anatomy has characteristics making this area more prone to pain than the other parts of the back. The foramina in the lumbar vertebrae are small, triangular, and narrow at the lateral angle at the L4-L5 vertebrae. The nerve roots are located in this lateral recess before exiting the intervertebral foramen more prone to compression. Each vertebra adjusts its shape and size as the reflection of the load it receives. The lumbar vertebrae has larger size than the other vertebrae, the load supported by the lower back is greater than the rest of the back and has more significant impact in trauma. The load received by the spine varies depending on the posture and external loads. The L3-L4 intervertebral discs in the sitting position receive higher load than when standing, the pressure is at the lowest when lying supine.26\n\nThe most common affected location in this study is the lower back in 22 (43.1%) patients. Low back pain is caused by osteophytes, facet hypertrophy, fractures and osteoporosis causing pain in the bones. Low back pain is also triggered by prolonged standing and heavy lifting and is mainly due to low hemoglobin which will improve after transfusion.28,29\n\nThe bone mass rapid turnover results from an imbalance between increased bone resorption and suppression of osteoclasts. This process is more common in the lumbar spine as a result of extramedullary erythropoiesis. The hemoglobin level before transfusion was 8.5-9 g/dL, it may be clinically tolerated by adults with thalassemia; nonetheless, the process of extramedullary erythropoiesis can continue to occur. It is recommended that the hemoglobin before transfusion be maintained at above 10 g/dL level to prevent extramedullary erythropoiesis in these patients' thalassemia. Decreased bone mass in thalassemia often occurs in the vertebral column and can manifest as spinal deformity, bone marrow compression, vertebral collapse, and intervertebral disc degeneration.30–32 Matrix metalloproteinases can underlie the arthritis occurrence.33 Pain in the lower back can also be caused by low bone density causing fractures and compression in the spinal cord.4 The most common finding in the vertebrae MRI examination is the degenerative vertebral disc with the highest prediction for L4-L5 intervertebral discs.34\n\nThe second most common location is the knee while the rest complain the pain in more than one location in the body such as in the joints of the fingers and toes, calves, ankles, ankles, heels and shoulders. This condition is also known as thalassemic osteoarthropathy.35\n\nThere is a role for Hypoxia Inducible Factor (HIF) in arthritis. HIF acts as the regulator of the adaptive response to hypoxia; hence, HIF is involved in the inflammation persistence and neovascular progression in arthritis. HIF has several target genes including erythropoietin (EPO) supporting the erythropoiesis. HIF is released under hypoxic conditions, yet it can also be released under normoxia by several inflammatory factors such as ROS, nitric oxide and proinflammatory cytokines such as IL-1β and TNF alpha.11,21\n\nHIF-1α hydroxylation is inhibited and accumulates in the cytoplasm under hypoxic conditions. This causes HIF-1α to be phosphorylated and translocated to the nucleus, in which it binds to the HIF-1β subunit to form a complex [HIF-α/HIF-1b]. This complex via HRE (Hypoxia Release Element) binds to a specific DNA sequence (5′TAGCGTGH3′) in the promoter region of several genes such as including EPO (erythropoietin). HIF-2α is the cartilage catabolism regulator working as a matrix-degrading enzyme and inflammation mediator (IL-1, IL-6, and TNF-α), increasing the expression of proteolytic enzymes and MMPs (Matrix Metalloproteinases), accelerating cartilage destruction and causing chondrocyte hypertrophy, all of which play the role in the arthritis development.36\n\nThis study showed that the subjects experienced improvement in the life quality after transfusion. Judging from the results of filling out the BPI-SF questionnaire by adults with TDT, 94.12% of the subjects experienced pain decrease after transfusion. It is found in Table 2 that there are significant differences between pain intensity and pain interfering with life obtained from BPI-SF scores before and after transfusion. This study is in line with the previous studies that revealed pain in thalassemia is commonly associated with low hemoglobin at the end of the transfusion cycle relieved by transfusion.1\n\nThis study emphasizes the importance of carrying out pain assessments for thalassemia patients. This study is the first to validate the BPI-SF tools into the Indonesian version and this questionnaire can be used in other studies as well related to chronic pain.\n\nThe following limitations are not further considered in this study. The examination was carried out to determine the pain etiology according to the fact that the subjects did not disclose their pain to the doctor when they went to the Hemato-Oncology Clinic. Most of the subjects knew their pain diagnose based on the results of filling out the BPI-SF questionnaire.\n\nFurther studies are needed to determine the pain etiology in adults with TDT, especially those related to low back pain and arthritis as the most common pain causes in adults with TDT using the cross-sectional approach.\n\n\nConclusion\n\nThe conclusion of this study is that the pain can occur in thalassemia patients due to low hemoglobin level and can be relieved with transfusion. There is the significant difference between pain intensity and pain interfering with life before and after transfusion.\n\n\nData availability\n\nF1000 Research: Data set 1. The data for BPI-SF validation per item question. https://doi.org/10.6084/m9.figshare.16984870\n\nData set 2. Demographic data of adult TDT patients. https://doi.org/10.6084/m9.figshare.17032340\n\nData set 3. The data of BPI-SF score and the hemoglobin level of adult TDT patients before and after transfusion. https://doi.org/10.6084/m9.figshare.17032361",
"appendix": "Acknowledgement\n\nWe would like to deliver our deepest gratitude to Medical Genetics Study Centre for the facilitation so that the research could be properly completed.\n\n\nReferences\n\nLal A: Assessment and Treatment of Pain in Thalassemia: Assessment and Treatment of Pain In Thalassemia. Ann. N. Y. Acad. Sci. 2016; 1368(1): 65–72. PubMed Abstract | Publisher Full Text\n\nHaines D, Martin M, Carson S, et al.: Pain in Thalassemia: The Effects of Age on Pain Frequency and Severity. Clin. Haematol. 2013: 151–165.\n\nTubman VN, Fung EB, Vogiatzi M, et al.: Guidelines for The Standard Monitoring of Patients with Thalassemia: Report of The Thalassemia Longitudinal Cohort. J. Pediatr. Hematol. Oncol. 2015; 37(3): e162–e169. Publisher Full Text\n\nGalanello R, Origa R: Beta-Thalassemia. Orphanet J. Rare Dis. 2010; 5(1): 11. PubMed Abstract | Publisher Full Text\n\nDanjou F, Anni F, Galanello R: Beta-Thalassemia: From Genotype to Phenotype. Haematologica. 2011; 96(11): 1573–1575. PubMed Abstract | Publisher Full Text\n\nViprakasit V, Ekwattanakit S: Clinical Classification, Screening and Diagnosis for Thalassemia. Hematol. Oncol. Clin. N. 2018; 32: 193–211. Publisher Full Text\n\nModell B, Darlison M: Global Epidemiology of Haemoglobin Disorders and Derived Service Indicators. Bull. World Health Organ. 2008; 86: 480–487. PubMed Abstract | Publisher Full Text\n\nPerwitasari E, Dalimoenthe NZ, Lismayanti L, et al.: Gambaran Hasil Screening Aloantibodi pada Pasien Tranfusion Dependent Thalassemia di RSUP Dr. Hasan Sadikin Bandung. J. Indon. Med. Assoc. 2017; 67: 584–590.\n\nCappellini M-D, Cohen A, Porter J, et al.: Guidelines for The Management of Transfusion Dependent Thalassaemia (TDT). 3rd ed.Cyprus:Thalassemia International Federation;2014.\n\nCarrasco C, Naziroǧlu M, Rodríguez AB, et al.: Neuropathic Pain: Delving into the Oxidative Origin and The Possible Implication of Transient Receptor Potential Channels. Front. Physiol. 2018; 9: 95. PubMed Abstract | Publisher Full Text\n\nSo K, Tei Y, Zhao M, et al.: Hypoxia-Induced Sensitization of TRPA1 in Painful Dysesthesia Evoked by Transient Hindlimb ischemia/Reperfusion in Mice. Sci. Rep. 2016; 6(1): 23261. PubMed Abstract | Publisher Full Text\n\nMcMahon SB, Koltzenburg M, Rtacey I, et al.: Wall and Melzack’s Textbook of Pain. 6th ed.Philadelphia:Elsevier;2013.\n\nNoureddine MHA, Taher AT, Haydar AA, et al.: Rheumatological Complications of Beta-Thalassaemia: An Overview. Rheumatology. 2018; 57(1): 19–27. PubMed Abstract | Publisher Full Text\n\nTsang S, Royse CF, Terkawi AS: Guidelines for Developing, Translating, and Validating A Questionnaire in Perioperative and Pain Medicine. Saudi J. Anaesth. 2017; 11: S80–S89. PubMed Abstract | Publisher Full Text\n\nBonafe FS, Campos LA, Maroco J, et al.: Brief Pain Inventory: A Proposal to Extend Its Clinical Application. Eur. J. Pain. 2019; 23: 565–576. PubMed Abstract | Publisher Full Text\n\nMajedi H, Dehghani SS, Soleyman-Jahi S, et al.: Validation of the Persian Version of the Brief Pain Inventory (BPI-P) in Chronic Pain Patients. J. Pain Symptom Manag. 2017; 54: 132–138.e2. PubMed Abstract | Publisher Full Text\n\nErdemoglu ÂK, Koc R: Brief Pain Inventory Score Identifying and Discriminating Neuropathic and Nociceptive Pain. Acta Neurol. Scand. 2013; 128: 351–358. PubMed Abstract | Publisher Full Text\n\nPoquet N, Lin C: The Brief Pain Inventory (BPI). J. Physiother. 2015; 62(1): 52. Publisher Full Text\n\nCarrasco C, Naziroglu M, Pecze L, et al.: Editorial: Involvements of TRP Channels and Oxidative Stress in Pain. Front. Physiol. 2018; 9: 1084. PubMed Abstract | Publisher Full Text\n\nRistoiu V, Shibasaki K, Uchida K, et al.: Hypoxia-Induced Sensitization of Transient Receptor Potential Vanilloid 1 Involves Activation of Hypoxia-Inducible Factor-1 Alpha and PKC. Pain. 2011; 152(4): 936–945. PubMed Abstract | Publisher Full Text\n\nGaber T: Hypoxia-Inducible Factor (HIF) in Rheumatology: Low O2! See What HIF Can Do!. Ann. Rheum. Dis. 2005; 64(7): 971–980. Publisher Full Text\n\nNemtsas P, Arnaoutoglou M, Perifanis V, et al.: Neurological Complications of Beta-Thalassemia. Ann. Hematol. 2015; 94(8): 1261–1265. PubMed Abstract | Publisher Full Text\n\nPapanastasiou DA, Ellina A, Baikousis A, et al.: Natural History of Untreated Scoliosis in β-Thalassemia. Spine. 2002; 27(11): 1186–1190. PubMed Abstract | Publisher Full Text\n\nNijs J: Low Back Pain: Guidelines for The Clinical Classification of Predominant Neuropathic, Nociceptive, or Central Sensitization Pain. Pain Physician. 2015;3; 3;18(3;5): E333–E346. Publisher Full Text\n\nPuntillo F, Giglio M, Paladini A, et al.: Pathophysiology of Musculoskeletal Pain: A Narrative Review. Ther. Adv. Musculoskelet. Dis. 2021; 13: 1759720X2199506. PubMed Abstract | Publisher Full Text\n\nMeliala L, Suryamiharja A, Purba JS, Sadeli HA: Nyeri Punggung Bawah. Kelompok Studi Nyeri. Indonesia:Perhimpunan Dokter Spesialis Saraf Indonesia (PERDOSSI);2003.\n\nGoubert D, Meeus M, Willems T, et al.: The Association Between Back Muscle Characteristics and Pressure Pain Sensitivity in Low Back Pain Patients. Scand. J. Pain. 2018; 18(2): 281–293. PubMed Abstract | Publisher Full Text\n\nCahya SA, Mardi Santoso W, Husna M, et al.: Low Back Pain. JPHV J. Pain Vertigo Headache. 2021; 2(1): 13–17. Publisher Full Text\n\nPiga A: Impact of Bone Disease and Pain in Thalassemia. Hematology. 2017; 2017(1): 272–277. PubMed Abstract | Publisher Full Text\n\nPerisano C, Marzetti E, Spinelli MS, et al.: Physiopathology of Bone Modifications in β-Thalassemia. Anemia. 2012; 2012: 1–5. Publisher Full Text\n\nKarimi M, Zarei T, Pishdad P: Extramedullary Hematopoiesis in A Patient With Transfusion Dependent Beta-Thalassemia Presenting with Cord Compression. IJBC. 2018; 10(1): 23–28.\n\nMoiz B, Khan HA, Raheem A, et al.: High Prevalence of Bone Pain and Fractures in Young Transfusion Dependent Patients with β-Thalassemia at Southern Pakistan. Ann. Hematol. Oncol. 2019; 6(2): id1234.\n\nAllegri M, Montella S, Salici F: Mechanism of Low Back Pain: A Guide for Diagnosis and Therapy. F1000Research. 2016; 1530: 1–11.\n\nOliveros O, Trachtenberg F, Haines D, et al.: Pain Over Time and Its Effects on Life in Thalassemia. Am. J. Hematol. 2013; 88(11): 939–943. PubMed Abstract | Publisher Full Text\n\nWiitavaara B, Fahlström M, Djupsjöbacka M: Prevalence, Diagnostics and Management of Musculoskeletal Disorders in Primary Health Care in Sweden – An Investigation of 2000 Randomly Selected Patient Records. J. Eval. Clin. Pract. 2017; 23(2): 325–332. PubMed Abstract | Publisher Full Text\n\nFernández-Torres J, Martínez-Nava GA, Gutiérrez-Ruíz MC, et al.: Role of HIF-1α Signaling Pathway in Osteoarthritis: A Systematic Review. Rev. Bras. Reumatol. Engl. Ed. 2017; 57(2): 162–173. Publisher Full Text"
}
|
[
{
"id": "232559",
"date": "08 Jan 2024",
"name": "Xuemei Zhen",
"expertise": [
"Reviewer Expertise My area of research is social medicine",
"health economic and policy."
],
"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:\nNeed to describe what is known about the issue based on current literature. Mention your study innovation. Need to state what the gap in the literature is and how this study helps to fill the gap in knowledge. Why choose adult patients? State what problems adult TDT patients have that impose more pain. The fourth paragraph should be mentioned in the Method section. The purpose of the study needs to be modified. The objective is not clearly stated or specific.\nMethod:\nPlease describe each instrument separately in the data collection section. The sample size formula should be mentioned and the calculation process should be explained to ensure that the sample size was sufficient for this study. What variables and data were collected? Validity and reliability of the instrument should be mentioned. If you used the Indonesian version of the instruments, please mention the references. Please describe each instrument more specifically and in detail. Mention the year of design of the BPI-SF questionnaire. Explain better why it was not possible to include a larger sample. In the statistical analysis, you mentioned “the data was obtained by telephone interview”. How were the interviews conducted? Is there a risk of bias in this situation? Please provide evidence of applying any measures of quality control such as \"cherries survey checklist\" or any other publicly available quality control measures.\nResult:\nIn the first paragraph, the presentation of the analytical methods and tools used should be contained in the Method section. In the second paragraph, “the duration of being diagnosed with thalassemia” needs to be mentioned in Table 1, as well as “other treatments taken”. Describe the educational level and employment status of the sample.\nDiscussion:\n\nFirst paragraph should include the most important findings of the study. In the third and fourth paragraph, the portion describing the lower back pain should be grouped into one paragraph. Please explain more about the comparison with the results of other studies rather than describing the principles that lead to pain. The discussion has not adequately compared the current study with other new studies. Many new studies have been conducted in the field of thalassemia patients in different countries. While the authors have used old references. Various variables have been examined in the study, but these variables have not been examined in the discussion. For example, the different demographic variables.\nStrengths and limitations\nSample size should be one of the limitations.\nConclusion\nMention the application of your findings in the fields of education, research, and clinical practice.\nReferences\nThe references are very old and not acceptable at all. At least 50% of the references should be from the last 5 years.\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": "12155",
"date": "09 Aug 2024",
"name": "Uni Gamayani",
"role": "Author Response",
"response": "Thank you for your review. I have revised my article and I sent it as version 2 article."
}
]
},
{
"id": "232558",
"date": "06 Feb 2024",
"name": "Noor Syahireen Mohammed",
"expertise": [
"Reviewer Expertise Health system policy"
],
"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 study provides a significant contribution to the understanding of pain experienced by thalassemia patients. The research's focus, methodology, significant results, and plausible findings are noteworthy. However, the study has certain limitations that restrict the generalizability of the findings. These limitations must be addressed as this would enhance the study's conclusions and help in developing better pain management strategies for thalassemia patients.\nIn detail, some of the strong points are: •\n\nClearly defined research question: The study investigates a relevant issue – pain management in adult TDT patients – with a specific and focused question about the impact of blood transfusion. •\n\nAppropriate sound methodology: The study utilizes valid inclusion and exclusion criteria, an appropriate sample size for paired data analysis, and established pain assessment tools with proper validity and reliability testing. •\n\nStatistically significant results: The observed decrease in pain intensity and interference following transfusion is statistically significant, supporting the main hypothesis. •\n\nPlausible explanation: The discussion provides a scientific explanation for the findings, linking pain reduction to improved haemoglobin levels and reduced activation of pain receptors. •\n\nWell-written and informative: The study is clearly presented and easy to understand, using appropriate language and structure.\nHowever, some improvements can be made on these points or addressed by author:\nIntroduction: •\n\nLacks a clear opening statement to capture the reader's attention and set the stage for the research. •\n\nCould benefit from a stronger connection between the background information and the research question. •\n\nMentions only one potential cause of pain (low haemoglobin) without acknowledging other possible contributors. •\n\nDoesn't explicitly state the hypothesis or main argument of the study. Methodology: •\n\nLimited information on sampling technique (random vs. convenience etc.) •\n\nPotential for bias in data collection due to self-reporting through telephone interviews. •\n\nLimited information on pain assessment methods beyond BPI-SF •\n\nLack of consideration for potential confounding variables (e.g., medication use, psychological factors). Results: •\n\nLimited generalizability due to potential bias and reliance on self-reported data. •\n\nNo analysis of other potential causes of pain besides low haemoglobin. Discussion: •\n\nLimited exploration of alternative explanations for pain beyond low haemoglobin and musculoskeletal involvement. •\n\nOffers limited explanation for the potential variation in individual responses and treatment effectiveness. •\n\nDoesn't discuss the limitations of pain assessment tools like BPI-SF in this context.\nIn conclusion, this study provides very useful information on pain management for Thalassemia patients. However, the study has some limitations that need to be addressed, such as the sampling technique, the potential for bias, and a need for a more comprehensive investigation into pain mechanisms. Addressing these limitations would help strengthen the conclusions and lead to more generalizability of the methodology to help with policymaking.\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?\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": "12154",
"date": "09 Aug 2024",
"name": "Uni Gamayani",
"role": "Author Response",
"response": "Thank you for your review. I have revised my article and I sent it as version 2 article."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1425
|
https://f1000research.com/articles/13-914/v1
|
09 Aug 24
|
{
"type": "Software Tool Article",
"title": "StackbarExtended: a user-friendly stacked bar-plot representation incorporating phylogenetic information and microbiota differential abundance analysis",
"authors": [
"Thibault Cuisiniere",
"Manuela M Santos",
"Manuela M Santos"
],
"abstract": "Background Microbial communities are mainly composed of bacteria, archaea, viruses and fungi, and are present in the gut, mouth, nose, skin, lungs, vagina, and bladder, among other places. In recent years, research has highlighted the critical role that these highly complex communities play in health and disease. Advances in sequencing technology have resulted in the development of high-dimensional data, which are challenging to effectively analyze and visualize. In this context, traditional stacked bar-plot visualizations, while widely used, fall short of conveying the fundamental phylogenic relationships between community members and are thus difficult to interpret.\n\nMethods StackbarExtended is implemented in native R, required version (≥ 4.0), and is platform independent, with its source code available on GitHub and archived on Zenodo.\n\nResults StackbarExtended allows for the plotting of relative abundance at user-defined taxonomic levels while displaying phylogenetic information using color gradients. Additionally, StackbarExtended integrates differential abundance statistics directly into the visualization process and performs clustering of low-abundance taxa.\n\nConclusions StackbarExtended offers researchers a user-friendly tool for rapid visualization, presentation, and analysis of the microbiota composition.",
"keywords": [
"Microbiota",
"differential abundance analysis",
"visualization"
],
"content": "Introduction\n\nMicrobiota communities consisting of diverse microbial members, including bacteria, viruses, fungi, and other microorganisms (Berg et al., 2020) in the digestive tract, skin, respiratory and urogenital systems, and other locations (Kennedy and Chang, 2020), have emerged as a crucial factor in maintaining health and preventing disease (Hou et al., 2022). With advancements in sequencing technologies (Satam et al., 2023) there is an increasing amount of data available on the composition and function of microbiota communities (Hasan and Yang, 2019), but analyzing and visualizing these data remain challenging due to their complexity and high dimensionality (Panek et al., 2018).\n\nMicrobiota communities are organized into multiple phylogenetic levels, including Phylum, Family, Genus, and Species, with each level providing unique insights into the community’s structure and functional potential (Jandhyala et al., 2015). Integrating visualization techniques to simultaneously represent relative abundances across multiple taxonomic levels would enhance the accessibility and ease of interpretation.\n\nStacked bar-plot representations of the relative abundance of microorganisms remain one of the most commonly used visualizations to show the global composition of microbiota communities, as well as potential shifts in a given community (Liu et al., 2021; McMurdie and Holmes, 2013). However, current tools used to generate stacked bar visualizations in microbiota analysis do not capture phylogenetic relationships between microbial taxa (Peeters et al., 2021). This is because traditional stacked bar visualizations utilize random colors to represent different microbes within the same taxonomic level. Furthermore, differential abundance analysis, a key step in interpreting statistically significant compositional shifts and their biological implications, is typically conducted and shown separately.\n\nTo address these issues, we developed a novel R package that allows users to easily generate stacked bar-plots to visualize microbiota composition at a user-defined taxonomic level while integrating information on taxa phylogeny through the use of color gradients. In addition, statistically significant differences in relative abundance are indicated on the plot. These simple solutions allow for more information to be communicated within one single graphical representation.\n\n\nMethods\n\nStackbarExtended is implemented in native R, required version (≥ 4.0), and is platform independent, with its source code available on GitHub and archived on Zenodo (Cuisiniere, 2024a).\n\nStackbarExtended is designed for microbiota data analysis and visualization. It requires three main inputs: a taxonomic table providing phylogenetic information, a count table detailing the abundance of the taxa, and metadata containing biological or experimental group data (Navgire et al., 2022). These tables can be obtained through established pipelines such as DADA2 (Callahan et al., 2016), Mothur (Schloss et al., 2009), and QIIME2 (Bolyen et al., 2019) in conjunction with reference databases such as Greengenes (DeSantis et al., 2006) or SILVA (Quast et al., 2013). The package supports a phyloseq S4 class object as an input, promoting a data management approach that regroups the count, taxonomy, and metadata tables into a single entity, thus simplifying data handling and enhancing reproducibility. The Phyloseq S4 object can be obtained through the phyloseq() function of the phyloseq R package (McMurdie and Holmes, 2013).\n\nOne of the StackbarExtended functionalities is the ability to handle multiple taxonomic levels simultaneously, typically focusing on user-defined levels set by default to Family (X) and Phylum (X+1). This is achieved through the use of the tax_glom() function from the phyloseq package. Most importantly, StackbarExtended uses a color-coding mechanism where taxa at a specified level (X) are visually differentiated using user-defined color palettes that match those of their Phylum level (X+1), making visual identification of the taxonomic hierarchies straightforward. This is achieved by applying different shades of the same color to represent individual taxa (X) within the same Phylum (X+1), creating a gradient effect that maps the phylogenetic taxonomy.\n\nAnother challenge in analyzing microbiota data is the large number of taxa present in the dataset. In microbiota communities, a small number of taxa typically dominate, while numerous others are present at significantly lower abundance levels (Neu et al., 2021). In classic stacked bar-plot representations such as the ones included in Phyloseq (McMurdie and Holmes, 2013), MicrobiomeAnalyst (Chong et al., 2020) or MicroEco (Liu et al., 2021) pipelines, these low-abundance taxa are simply filtered out before plotting. StackbarExtended allows users to classify taxa based on their relative abundance, and, by default, the package plots only taxa representing more than 1% of the total abundance. In addition, low-abundance taxa (X) can be grouped into their respective “Others” taxonomic level and the information about their taxonomy (i.e. Phylum) is kept while taxa belonging to low abundance Phyla (X+1) are grouped into a general “Others” category. Thus, by still including the low-abundance taxa, StackbarExtended provides a more accurate representation of the taxa in a microbiota community.\n\nFinally, StackbarExtended includes DESeq2 differential abundance analysis functionality (Love et al., 2014) which allows users to statistically assess the difference in taxa abundance between experimental groups and apply fdr corrections. Significant features (i.e. taxa with significant differences in abundance between 2 groups) are highlighted in the legend using bold font, and the significance levels (p-value) after fdr corrections are automatically shown using stars in the legend. When more than two treatment groups are compared, multiple pairwise comparisons can be computed and data-frames are produced with results providing information about the taxa identified as significant at each phylogenetic level analyzed through the DESeq2 analysis. This information includes the taxa names and phylogeny, their corresponding abundance levels, statistical metrics such as log2 fold-change, p-values and fdr-corrected p-values.\n\nTo demonstrate the use of this package, we have provided ready-to-use example data “ps” from our previously published study (Cuisiniere, 2024a; Cuisiniere et al., 2021) which assessed shifts in mouse gut microbiota composition after antibiotic treatment (Figure 1).\n\nMice (n = 9) received oral antibiotic treatment with neomycin and metronidazole for one week. Fecal samples were collected before (Day 0) and after antibiotic treatment (Day 7). 16S rRNA of DNA extracted from fecal samples was sequenced using the Illumina MiSeq platform. The 4 most abundant phyla and families are represented. Families with a mean abundance lower than 1% across the samples are regrouped into “Others”. Taxa represented in bold within the legends are statistically significant after fdr correction (*P < 0.05, **P < 0.01, ***P < 0.001). Data used are from the “ps” dataset and are included in the StackbarExtended R package.\n\nAnimal experiments were approved by the Institutional Animal Care committee of the Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM) in agreement with the guidelines of the Canadian Council of Animal Care. The study was carried out in compliance with the ARRIVE guidelines (Cuisiniere, 2024b). No criteria were set for including and excluding animals during the experiment or data points during the analysis. No exclusions of animals, experimental units, or data points were applied for the analysis.\n\nIn order to obtain the data, four-week-old female C57Bl/6 mice were purchased from Charles River Laboratories (Saint-Constant, QC, Canada). Constant efforts were made to minimize the suffering of the animals. Nine mice were kept under controlled specific pathogen free (SPF) conditions in the CRCHUM animal facility at a temperature of 22°C, 45-60% humidity with a light-dark cycle of 12-12. They were housed at three mice per cage with ad libitum access to chow and water. Cages were enriched with nesting material. Mice were allowed one week of acclimation following arrival to the CRCHUM animal facility, after which oral antibiotics consisting of metronidazole (1 mg.ml−1, Hospira, St-Laurent, QC, Canada) and neomycin (1 mg.ml−1, Sigma, St-Louis, MO, USA) were added to the drinking water for one week. Fecal samples were collected before (Day 0) and after antibiotic treatment (Day 7), snap-frozen and stored at -80°C. Mice were then euthanized using CO2 followed by cervical dislocation. DNA was extracted using the Qiagen DNeasy PowerSoil® kit (Qiagen, Toronto, ON) and quantified using a spectrophotometer (DeNovix DS-11 FX, Wilmington, DE). The 16S ribosomal RNA (rRNA) library preparation and sequencing was performed using the Illumina MiSeq platform at Genome Québec targeting the V3-V4 (Primers: 341F, 805R) region of the 16S rRNA gene. Forward and reverse, raw, demultiplexed 16S rRNA reads were denoised, chimera filtered, and clustered into sequence variants using the Dada2 package (version 1.16) (Callahan et al., 2016) in R (version 4.0.1). Reads were trimmed at the first instance of a quality score less than or equal to 2 or removed if they contained ambiguous nucleotides (N) or if two or more errors were expected based on the quality of the trimmed read. After taxonomic assignment using Silva training set v132 (Quast et al., 2013), ASV (Table 1), taxonomy (Table 2) and metadata (Table 3) were combined into a phyloseq object (McMurdie and Holmes, 2013).\n\nRows represent each sample and columns represent individual ASVs. Each cell indicates the count of a particular ASV in a specific sample.\n\nRows represent individual ASVs, and columns represent each taxonomic rank. Each cell contains the taxonomic name at that rank for the corresponding ASV.\n\nRows contain metadata associated with each sample.\n\nUsers can then use the following code to create graphical representation of the gut microbiota composition at the phylum and family levels comparing mice before and after antibiotic treatment and performing differential abundance with fdr correction.\n\nIn addition to the graphical representation, two output tables (one for each level) are created containing statistical information concerning the differentially abundant taxa (Table 4). The tables can be accessed as follows:\n\nThe data frame output contains the results columns: baseMean, log2FoldChange, lfcSE, stat, pvalue (unajusted p-values) and padj (fdr-corrected p-values), and also includes metadata columns of related taxonomic information. The lfcSE gives the standard error of the log2FoldChange. For the Wald test, stat is the Wald statistic: the log2FoldChange divided by lfcSE, which is compared to a standard Normal distribution to generate a two-tailed pvalue. For the likelihood ratio test (LRT), stat is the difference in deviance between the reduced model and the full model, which is compared to a chi-squared distribution to generate a p-value.\n\nThe primary objective of our example dataset is to identify which taxa at the Family and Phylum levels were impacted by antibiotic treatment in mice gut microbiota. This analysis is crucial for understanding how antibiotic interventions alter microbial communities. The graphical output (Figure 1) provided a clear assessment, revealing that among the four most abundant Phyla, three were significantly affected by the antibiotic treatment. Specifically, significant alterations were observed in Verrucomicrobia, Bacteroidetes, and Proteobacteria (fdr < 0.05), indicating a substantial shift in the microbial composition due to antibiotic exposure. Among the abundant Families (>1% of the total abundance) within these Phyla, 10 out of 11 exhibited significant alterations (fdr < 0.05). On average, the six remaining low-abundance Phyla, grouped into the “Others” category, accounted for 2.5% of the total relative abundance. Similarly, within the abundant Phyla, the 14 low-abundance Families accounted for 2.4% of the total relative abundance.\n\nThe two generated output tables provide detailed statistical information about the differentially abundant taxa at each level, including log2 fold-change, exact p-values, and fdr-corrected p-values. This comprehensive data allows for identification of taxa significantly impacted by the treatment. Notably, four additional low-abundance Phyla - Cyanobacteria, Deferribacteres, Tenericutes, and Actinobacteria - were found to be significantly affected (fdr < 0.05). Furthermore, a total of 24 families were identified as statistically different (fdr < 0.05) (Cuisiniere, 2024a).\n\nThese findings are consistent with previous studies that have reported significant shifts in gut microbiota composition following antibiotic treatment (Fishbein et al., 2023). Hence, this use case demonstrated the advantage of using StackbarExtended to present a clear and interpretable graphical representation while retaining the capacity to perform detailed statistical analysis.\n\n\nDiscussion\n\nStackbarExtended offers the opportunity to enhance the widely utilized stacked bar graphical representation by incorporating information about taxonomy and statistical significance in regard to differentially abundant taxa. Furthermore, it enables users to retain data on rare taxa while maintaining phylogeny information. These functionalities have been implemented into a user-friendly R package, StackbarExtended, which is freely accessible on GitHub. The package facilitates the processing of large microbiota datasets and produces publication-ready and information-rich graphical representations with a high level of personalization. StackbarExtended is particularly useful to biology and molecular biology students, fellows and researchers working in microbiota analysis, and its output visualizations are suitable for publications and time-limited presentations at conferences and seminars requiring quick interpretation of displayed data.\n\n\nSoftware availability\n\nSource code available from: https://github.com/ThibaultCuisiniere/StackbarExtended.\n\nArchived software available from: https://doi.org/10.5281/zenodo.11166800 (Cuisiniere, 2024a).\n\nLicense: This R package and underlying data are freely available under the Gnu Public License (GPL-3).\n\n\nEthics and consent\n\nAnimal experiments were approved on April 3rd 2019 by the Institutional Animal Care committee of the Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM) in agreement with the guidelines of the Canadian Council of Animal Care, approval number C19006MSs. The study was carried out in compliance with the ARRIVE guidelines (Cuisiniere, 2024b).",
"appendix": "Data availability\n\nThe dataset analyzed in this study is stored in the data/directory of the StackbarExtended package.\n\nARRIVE checklist available from: https://zenodo.org/records/12583605 (Cuisiniere, 2024b).\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 thanks Marco Constante (Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada) for his insight in developing the StackbarExtended package. We also thank Claire Gerkins and Claire McCartney (Nutrition and Microbiome Laboratory, Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada) for their help in editing the manuscript.\n\n\nReferences\n\nBerg G, et al.: Microbiome definition re-visited: old concepts and new challenges. Microbiome. 2020; 8(1): 103. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBolyen E, et al.: Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 2019; 37(8): 852–857. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCallahan BJ, et al.: DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods. 2016; 13(7): 581–583. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChong J, et al.: Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data. Nat. Protoc. 2020; 15(3): 799–821. PubMed Abstract | Publisher Full Text\n\nCuisiniere T: StackbarExtended. Zenodo. 2024a. Publisher Full Text\n\nCuisiniere T: tackbarExtended - ARRIVE checklist. Zenodo. 2024b. Reference Source\n\nCuisiniere T, et al.: Oral iron supplementation after antibiotic exposure induces a deleterious recovery of the gut microbiota. BMC Microbiol. 2021; 21(1): 259. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDeSantis TZ, et al.: Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 2006; 72(7): 5069–5072. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFishbein SRS, Mahmud B, Dantas G: Antibiotic perturbations to the gut microbiome. Nat. Rev. Microbiol. 2023; 21(12): 772–788. PubMed Abstract | Publisher Full Text\n\nHasan N, Yang H: Factors affecting the composition of the gut microbiota, and its modulation. PeerJ. 2019; 7: e7502. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHou K, et al.: Microbiota in health and diseases. Signal Transduct. Target. Ther. 2022; 7(1): 135. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJandhyala SM, et al.: Role of the normal gut microbiota. World J. Gastroenterol. 2015; 21(29): 8787–8803. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKennedy MS, Chang EB: The microbiome: Composition and locations. Prog. Mol. Biol. Transl. Sci. 2020; 176: 1–42. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu C, et al.: microeco: an R package for data mining in microbial community ecology. FEMS Microbiol. Ecol. 2021; 97(2). PubMed Abstract | Publisher Full Text\n\nLove MI, Huber W, Anders S: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12): 550. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcMurdie PJ, Holmes S: phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One. 2013; 8(4): e61217. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNavgire GS, et al.: Analysis and Interpretation of metagenomics data: an approach. Biol. Proced. Online. 2022; 24(1): 18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNeu AT, Allen EE, Roy K: Defining and quantifying the core microbiome: Challenges and prospects. Proc. Natl. Acad. Sci. USA. 2021; 118(51). PubMed Abstract | Publisher Full Text | Free Full Text\n\nPanek M, et al.: Methodology challenges in studying human gut microbiota - effects of collection, storage, DNA extraction and next generation sequencing technologies. Sci. Rep. 2018; 8(1): 5143. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeeters J, et al.: Exploring the Microbiome Analysis and Visualization Landscape. Front. Bioinform. 2021; 1: 774631. PubMed Abstract | Publisher Full Text | Free Full Text\n\nQuast C, et al.: The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013; 41(Database issue): D590–D596. PubMed Abstract | Publisher Full Text\n\nSatam H, et al.: Next-Generation Sequencing Technology: Current Trends and Advancements. Biology (Basel). 2023; 12(7). Publisher Full Text\n\nSchloss PD, et al.: Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 2009; 75(23): 7537–7541. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "312942",
"date": "14 Aug 2024",
"name": "Zheng Sun",
"expertise": [
"Reviewer Expertise microbiome methodology development"
],
"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\nInteresting tool! It provides a clear and effective visualization of microbiome data, particularly by using similar colors to represent genus and its corresponding higher family, which enhances human interpretability. To further improve the tool, I suggest the following: (1) Adapt the tool to be easily applied to WMS data by integrating a phylogenetic tree from the GTDB/RefSeq database; (2) Replace lfcSE with AMCOM to better address the compositionality issue; (3) Expand the color palette and include detailed guidance on its use in the help documentation.\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": []
},
{
"id": "312937",
"date": "29 Aug 2024",
"name": "Monica Steffi Matchado",
"expertise": [
"Reviewer Expertise Microbiome and 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\nOverview: This manuscript describes a new R package, StackbarExtended, which combines phylogenetic information and statistical significance into a single graphical output. This will visually improve microbiota composition in better understanding. The technique solves conventional stacked bar plot shortcomings, most notably the separation of differential abundance analysis from visual depiction and the absence of evolutionary context. The manuscript is well-written, the methodology is sound, and the use case effectively demonstrates the package's capabilities. Major comments: 1. The package appears to focus only to users who are familiar with R programming knowledge. There is no discussion on how the package might be made more accessible to a broader audience, such as through a user-friendly interface or integration with other platforms. This limits the potential impact and adoption of the tool in the wider research community. Are there any plans to develop a graphical user interface (GUI) or Shiny app to make the package more accessible to users who may not be proficient in R? This could significantly broaden the tool’s usability, particularly among biologists without extensive programming experience. 2. The manuscript presents examples only up to the Family level, raising concerns about how the package would handle more detailed taxonomic levels, such as Genus. Given that a single Phylum can contain numerous Genera, the proposed colour scheme might become overly complex and difficult to interpret at these lower levels. The manuscript does not address how the tool will manage the increased number of taxa or how it will prevent the visualization from becoming visually cluttered and messy. This is a critical issue that needs to be resolved to ensure that the tool remains effective at higher taxonomic resolutions. 3. Incorporating a measure of prevalence into the visualization would be a valuable addition to the StackbarExtended package, particularly since the package does not require users to filter out low-abundance taxa. Showing the prevalence of taxa across sample groups can provide important context for interpreting the data, especially when dealing with low-abundance taxa that might still play significant ecological or biological roles despite their low relative abundance. 4. If possible, consider implementing interactive plots where users can hover over a bar segment to see detailed information, including the prevalence of that taxon across the sample groups. This approach would make the visual representation more informative without overcrowding the static plot. 5. Also consider an interactive feature where users can click on the \"Others\" category in the stacked bar plot to reveal a separate table or plot detailing the low-abundance taxa would significantly enhance the usability and depth of analysis in StackbarExtended. This feature would allow users to explore the \"hidden\" diversity within their microbiota data without overcrowding the primary visualization. 6. Incorporating the ability for users to customize the threshold for filtering (default 1%) for including taxa in the visualization is essential, especially given the diversity of microbial environments that researchers may be working with. While the default 1% threshold may be suitable for many studies, environments characterized by low-abundance microbial communities could require a lower threshold to capture significant taxa that would otherwise be excluded.\nConclusion: Overall, StackbarExtended is a good contribution to the field of microbiota research. The manuscript is well-structured, and the tool itself is innovative and highly applicable. Addressing the major comments will significantly strengthen the manuscript.\n\nIs the rationale for developing the new software tool clearly explained? Partly\n\nIs the description of the software tool technically sound? Partly\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? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-914
|
https://f1000research.com/articles/11-729/v1
|
01 Jul 22
|
{
"type": "Systematic Review",
"title": "The relationship of age, sex and prothrombin time related to the severity and mortality of COVID-19 patients with diabetes mellitus: a systematic review and meta analysis",
"authors": [
"Audrey Fabianisa Mirza",
"Ceria Halim",
"Mutiara Indah Sari",
"Audrey Fabianisa Mirza",
"Ceria Halim"
],
"abstract": "Background: SARS-CoV-2 first appeared in Wuhan, China, in December 2019. Looking at the prevalence data in the world and in Indonesia, the highest mortality rate due to COVID-19 involves age, gender and comorbidities such as diabetes mellitus. Severity of the condition also refers to coagulation abnormalities, such as abnormal prothrombin time values. Methods: This systematic review study and meta-analysis used online literature sourced from PubMed, Science Direct, EBSCO, Cochrane and Google Scholar. The literature used here is literature that has data on age, sex and prothrombin time of COVID-19 patients with diabetes mellitus whose quality is assessed by the NOS (Newcastle-Ottawa Scale) criteria and processing data using Review Manager 5.4. Results: Out of 8711 literatures that were traced from various search sources, there were 46 literatures that were included in this study. The results of the analysis on age showed the Standardized Mean Difference (SMD) value of 0.45 and P <0.0001 (95% CI: 0.23–0.68), the gender analysis showed an Odds Ratio (OR) value of 3.28 and P = 0.01 (95% CI: 1.26–8.52) and the prothrombin time analysis showed SMD values of 0.41 and P = 0.07 (95%CI = -0.03–0.85). Conclusion: A person who is infected with COVID-19 and has comorbid diabetes mellitus has a high risk of disease severity and mortality if he is older and male.",
"keywords": [
"age",
"sex",
"prothrombine time",
"COVID-19",
"diabetes mellitus"
],
"content": "Introduction\n\nSARS-CoV-2 first appeared in Wuhan, China, on December 31, 2019 and quickly spread throughout the world. As of April 13, 2021, a total of 136,291,755 confirmed cases of COVID-19 infection with 2,941,128 confirmed cases of death have been reported in 223 countries and territories worldwide.1 In Indonesia, according to the National Development Planning Agency/Bappenas, the first confirmed case of COVID-19 was on March 2, 2020. On April 14, 2021, there were 1,577,526 positive confirmed cases and 42,782 for the number of deaths (2.7% of the national confirmed number).2\n\nDiabetes mellitus (DM) is an independent prognostic factor for COVID-19 patients. The survival rate of diabetic patients is lower, and the time from the on-set of the infection to death is shorter than that of non-diabetic patients.3 The mechanism of expression of angiotensin-converting enzyme 2 (ACE2) is increased in lung and other tissues of DM patients. This upregulation is associated with chronic inflammation, activation of endothelial cells and insulin resistance which exacerbates the inflammatory response, in short, the clinical course and prognosis of COVID-19 in DM patients is significantly worse.4\n\nThere is an increase in the number of cases and a greater risk of severe disease with age.5 The increase in male mortality is related to the regulation of ACE2 and the body's immune system.6 DM patients are in a prothrombotic state due to hyperglycemia and chronic hyperinsulinism.7\n\nStudies on COVID-19 associated with diabetes comorbid conditions have been studied by several researchers. However, the results obtained regarding age, gender and prothrombin time showed a lot of variability, so further exploration is needed to determine the effect of diabetes on COVID-19. This systematic review and meta-analysis aims to examine the relationship between age, gender and prothrombin time on the severity and mortality of COVID-19 patients with comorbid DM compared to non-DM.\n\n\nMethods\n\nThis research was conducted after obtaining approval from the Health Ethics Commission of Universitas Sumatera Utara (EC No.789/KEP/USU/2021). This study used online literature from PubMed, Science Direct, EBSCO, Cochrane and Google Scholar. The journals used were those which captured the data on COVID-19 patients having comorbid DM, accompanied by data on age, sex and prothrombin time values. The literature search was carried out according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analysis). The Checklist used in this meta-analysis was the PRISMA 2009 checklist.\n\nThis research was conducted in Medan, North Sumatra and was conducted between July–October 2021. Literature search with the keywords “Age” AND (“Sex” OR “Gender”) AND (“Prothrombin Time” OR “PT”) AND (“COVID-19” OR “SARS CoV-2”) AND (“Diabetes Mellitus” OR “DM”).\n\nAll retrospective studies (cross-sectional, cohort and case-control) that had data on patients’ age, sex and prothrombin time values who had been hospitalized either on the ward or in the ICU were considered eligible for this study. Eligible studies compared data on age in DM and non-DM patients, gender in DM patients and prothrombin time values in DM and non-DM patients.\n\nAll duplications were removed at the initial screening, followed by a second screening in which articles that did not meet the inclusion criteria were removed, such as review articles, systematic reviews, meta-analytical studies, comments, letters, animal studies and studies that were not in Indonesian or English.\n\nThe quality of the literature used in this study was determined based on criteria of NOS (The Newcastle Ottawa Scale) and for the selection a score of 7–9 (high quality study) was used.\n\nAll relevant data was collected using data collection standards that had been set by two reviewers (AFM and MIS). The data taken for the age variable was the Mean and Standard Deviation (SD) of COVID-19 patients with DM and non-DM, the gender variable noted the Odds Ratio (OR) and Standard Error (SE) data from COVID-19 patients with DM, the variables taken for prothrombin time were the median and Interquartile range (IQR) which are converted into the Mean and SD of COVID-19 patients with DM and non-DM. Data was obtained from patients who had COVID-19 confirmed through reverse-transcriptase polymerase chain reaction (RT-PCR). These patients were interviewed regarding congenital diseases and blood tests was used to determine whether they had DM before being admitted to the hospital.\n\nThis study used Review Manager 5.4 software (The Cochrane Collaboration, Oxford, UK) (RevMan, RRID:SCR_003581).55 Standardized Mean Difference (SMD) and OR were used to analyze the variables in this study. The Confidence Interval (CI) was set at 95%. P value less than 0.05 indicated statistically significant data. Chi Square test was used to assess the heterogeneity of statistical data with the symbol I2. If the I2 test was worth more than 50%, it indicated that there was heterogeneity between studies and the study was conducted using a random effects model. If the I2 test was less than 50%, it indicated that there was homogeneity between studies, the research was carried out using a fixed effects model.\n\n\nResults\n\nIn the initial search, we found 8711 articles which can be seen in Figure 1. The final results after selection got a total of 46 articles that were included in this meta-analysis study.\n\nThis meta-analysis study included literature examining two groups, namely COVID-19 patients (controls) and COVID-19 patients with DM. Data from both groups were taken from medical records of patients who were treated either in the ward or in the Intensive Care Unit (ICU). Characteristics of patients based on the study literature are seen in Table 1.\n\nBased on the entire literature that was included as many as 46 researched in 2020–2021, the most research was carried out in 2021 in as many as 28 studies. The country that researched the most literature in this meta-analysis was China, which was the initial location for the spread of COVID-19 as per as many as 21 literatures. Some studies have a small sample size, but the samples studied are COVID-19 patients who have been hospitalized and have moderate-severe symptoms so that they represent a patient population with a high risk of severity and mortality.\n\nThe literature that was included in the age distribution associated with the incidence of COVID-19 in DM and non-DM was 31 literatures. Among them were 3 literature cross-sectional research designs, 9 literature cohorts and 19 case-control literatures. Characteristics of age in patients based on the study literature can be seen in Table 2.\n\nBased on Table 2, the age distribution of the incidence of COVID-19 with DM compared to non-DM, almost all studies have data on patients with DM having an older age. Forest plot analysis of the relationship between age and the incidence of COVID with DM and non-DM can be seen in Figure 2.\n\nThe results of the literature analysis in the sub-group of cross-sectional study designs to see the comparison of age in COVID-19 patients with DM and non-DM resulted in I2 = 87% indicating heterogeneity between studies. Subtotal SMD was 0.42 (95%CI = 0.07–0.78; P = 0.02) which indicates that the result was significant because P < 0.05 and the diamond did not touch the vertical line.\n\nThe results of the analysis in the cohort study design sub-group to see the comparison of age in COVID-19 patients with DM and non-DM resulted in I2 = 98% which indicates heterogeneity between studies. Subtotal SMD was 0.63 (95%CI = 0.29–0.98; P = 0.0003) which is that the result was significant, because P < 0.05 and the diamond did not touch the vertical line.\n\nThe results of the analysis in the case-control study design sub-group to see the comparison of age in COVID-19 patients with DM and non-DM resulted in I2 = 98% which indicates heterogeneity between studies. Subtotal SMD was 0.37 (95%CI = 0.11–0.63; P = 0.006) which indicates that the result was significant because P < 0.05 and the diamond did not touch the vertical line.\n\nThe results of the literature analysis to see the comparison of age in COVID-19 patients with DM and non-DM as a whole resulted in a value of I2 = 99% which indicated heterogeneity between studies, so the random effects model was used. Total SMD 0.45 (95%CI = 0.23–0.68; P < 0.0001) with a population confidence interval of 0.23 to 0.68 (P < 0.0001) indicating there is a significant result because P < 0.05. In addition, the diamond did not touch the vertical line thus proving that COVID-19 patients with DM have an older age compared to COVID-19 patients without comorbid DM who are hospitalized.\n\nThe literature that was included in the sex distribution was associated with the incidence of COVID-19 in DM as many as 5 literatures. Among them were 2 literature cross-sectional research designs and 3 literature cohorts. Gender characteristics of patients based on the study literature can be seen in Table 3 below.\n\nBased on Table 3, the sex distribution of the incidence of COVID-19 with DM, overall data on the OR value shows that male patients are more at risk of exposure to the disease than women. The forest plot analysis of the sex relationship with the incidence of COVID with DM can be seen in Figure 3.\n\nBased on the results of the picture of the size of the square on the forest plot, the research by Ortega et al. (2021) has the largest square proportional to the greater weight value because it has a larger sample than other studies and has more influence on the results of this forest plot.\n\nThe results of the analysis on the sub-group cross-sectional study design to see the sex comparison in COVID-19 patients with DM resulted in I2 = 0% which indicated the absence of heterogeneity between studies. Subtotal OR 1.44 (95%CI = 1.07–1.94; P = 0.02) which stated that the results were significant because P < 0.05 and the diamond did not touch the vertical line.\n\nThe results of the analysis on the cohort study design sub-group to see the sex comparison in COVID-19 patients with DM resulted in I2 = 0% which indicated no heterogeneity between studies. Subtotal OR 5.71 (95%CI = 2.44–13.36; P < 0.0001) which indicates that the results were significant because P < 0.05 and the diamond did not touch the vertical line.\n\nThe results of the literature analysis to see the sex comparison between men and women in COVID-19 patients with DM overall yielded a value of I2 = 59% which indicated heterogeneity between studies, so the random effects model was used. Total OR 3.28 (95% CI = 1.26–8.52; P = 0.01) with a confidence interval for the population between 1.26 to 8.52 (P = 0.01) indicated that the results were significant because P < 0.05. In addition, the diamond did not touch the vertical line, thus proving that male COVID-19 patients with comorbid DM were more at risk of contracting the disease than female patients.\n\nFifteen literature included the distribution of prothrombin time values associated with the incidence of COVID-19 in DM and non-DM. Among them were 7 literature cohort research designs and 8 case-control literatures. Characteristics of prothrombin time in patients based on the study literature can be seen in Table 4 below.\n\nBased on Table 4, the distribution of prothrombin time values in the incidence of COVID-19 with DM is compared with non-DM in the form of Median and IQR converted into the Mean and SD which has been converted in Table 4.\n\nOverall, it shows that the prothrombin time value in patients with DM has a slightly higher value compared to non-DM and as many as 3 studies have the opposite data. Forest plot analysis of the relationship between prothrombin time and the incidence of COVID with DM and non-DM can be seen in Figure 4.\n\nThe results of the literature analysis in the cohort study design subgroup to compare the prothrombin time values in COVID-19 patients with DM and non-DM resulted in I2 = 99% which indicated heterogeneity between studies. Subtotal Standardized Mean Difference (SMD) 0.15 (95%CI = -0.88–1.18; P = 0.78) which means that the result was not significant because P > 0.05 and the diamond touched the vertical line.\n\nResults of literature analysis in the case-control study design sub-group to compare the prothrombin time values in COVID-19 patients with DM and non-DM produced I2 = 92% which indicated heterogeneity between studies. Subtotal Standardized Mean Difference (SMD) 0.61 (95%CI = 0.31–0.91; P < 0.0001) which means that the result is significant because P < 0.05 and the diamond did not touch the vertical line.\n\nThe results of the literature analysis to see the comparison of the prothrombin time value in COVID-19 patients with DM and COVID-19 patients without a history of DM overall yielded a value of I2 = 98% which indicated heterogeneity between studies, so the random effects model was used. Total Standardized Mean Difference (SMD) 0.41 (95%CI = -0.03–0.85; P = 0.07) with a confidence interval for the population between -0.03 to 0.85 (P = 0.07) showed that there were insignificant results because P < 0.05. In addition, the diamond touched the vertical line thus proving that the prothrombin time value was the same in both COVID-19 patients with DM and COVID-19 patients who did not have comorbid DM before being hospitalized.\n\n\nDiscussion\n\nThis systematic review and meta-analysis included 46 articles with a total number of 1,325,334 patients who were positive for COVID-19 and divided into diabetic and non-diabetic groups which were analyzed for age, sex and prothrombin time values.\n\nDiabetes is reported to be one of the comorbidities that increases the progression and mortality of COVID-19. Diabetes can be a risk factor because of the increase in serum ACE2 in diabetic patients. In addition, patients taking inhibitors of angiotensin-converting enzyme (ACEIs) and angiotensin II receptor blockers (ARBs) showed overexpression of ACE2, the COVID-19 entry receptor.8\n\nThe results of a systematic study and meta-analysis on the age variable, showed that patients with COVID-19 with DM were significantly older than non-diabetic patients. There is a correlation between age and the innate immune system as has been reviewed elsewhere and concluded that the elderly are particularly susceptible to developing more infections because the innate immune system declines gradually with older age.9\n\nThe relationship between age and the incidence of COVID-19 in the DM group compared to non-DM is in line with several research results which state that patients infected with COVID-19 with comorbid diabetes are older than non-diabetics. In both patients with or without diabetes the severity of the disease increases with age.10 Another study also found that diabetic patients were significantly older and had more severe symptoms than non-diabetic patients,11 the COVID-19 patients with diabetes had a higher age than non-diabetics,12 COVID-19 patients with pre-existing diabetes were older than those without.7 Another study stated that diabetic and non-diabetic population significantly different in age but a slightly older non-diabetic population.13\n\nThe results of the study on the gender variable, showed that men were more at risk of exposure to the disease and had more severe symptoms than women. Gender differences affect clinical outcome and prognosis, with males at higher risk than females. Male patients may express higher ACE2 which is regulated by male sex hormones.9\n\nThe relationship between sex and the incidence of COVID-19 in the DM group is in line with several research results, such as having a much larger male population than female,14 twice as many male patient subjects as confirmed positive for COVID-198, the presentation of diabetic men at high risk of mortality and the number of hospitalizations is higher in diabetic men than women and in other comorbid diseases.15 In contrast to a study, in the data there were more female patients than men, although there were more men in the diabetes group than non-diabetics but in both groups had more female patients.16\n\nThe prothrombin time variable showed the same prothrombin time value in both diabetic and non-diabetic patients. Theoretically, COVID-19 patients with DM have a prolonged prothrombin time value, as well as the results in the case-control study design sub-group as seen in Figure 3 which shows a difference, namely a prolonged prothrombin time value in the DM group. Diabetic patients in a prothrombotic state due to hyperglycemia and chronic hyperinsulinism make all phases of coagulation abnormal.7 Non-survivors have a prolonged prothrombin time compared to survivors. The timing of increases in D-dimer, prothrombin time, and activated partial thromboplastin time, with decreased fibrinogen and platelet counts, also coincided with the duration of hospitalization, ranging from 7 to 10 days after admission. Patients who are still hospitalized or have good prognostic factors are likely to have non-prolonging prothrombin time.54\n\nThe relationship between prothrombin time and the incidence of COVID-19 in the DM and non-DM groups is in line with several studies.17 The prothrombin time values in both groups were relatively the same and did not prolong.12 The prothrombin time values were almost the same in both groups and within the normal range.10 In contrast to a study that showed a slight difference in the prothrombin time value in the diabetic group, which was prolonged compared to the non-diabetic group, which was still within normal limits.18\n\nThis study has research limitations, there are only a few studies on COVID-19 with DM as the outbreak only occurred at the end of 2019. Research on COVID-19 with DM is relatively new, and it needs to be studied further.\n\n\nConclusion\n\nPatients with old age with diabetes tend to have more severe disease than non-diabetics.\n\nPatients with diabetes who are hospitalized are more likely to be male, indicating that males are more susceptible to severe disease. The prothrombin time values in both diabetic and non-diabetic groups tended to be the same and within normal limits.\n\nResearchers are expected to conduct further studies on the relationship between age and gender in COVID-19 patients with DM, so that the data obtained from the results of this meta-analysis are more relevant when applied in Indonesia.\n\nClinicians are expected to provide health care, especially for patients with DM who are old and male in the era of the COVID-19 pandemic to reduce the risk factors for severity and mortality of diabetic patients being infected with COVID-19.\n\nResearchers are expected to conduct further studies on prothrombin time in COVID-19 patients with DM for a more detailed understanding.\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\nFigshare: PRISMA checklist for ‘The relationship of age, sex and prothrombin time related to the severity and mortality of COVID-19 patients with diabetes mellitus: a systematic review and meta analysis’. https://doi.org/10.6084/m9.figshare.18865103.56\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAuthor contributions\n\nAudrey Fabianisa Mirza: Conceptualization, formal analysis, methodology, investigation, visualization, writing – original draft preparation, writing – review & editing.\n\nCeria Halim: Formal analysis, writing – original draft preparation, writing – review & editing.\n\nMutiara Indah Sari: Conceptualization, formal analysis, methodology, project administration, supervision, funding acquisition.",
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Publisher Full Text\n\nMansour A, Sajjadi-Jazi SM, Kasaeian A, et al.: Clinical characteristics and outcomes of diabetics hospitalized for COVID-19 infection: a single-centered, retrospective, observational study. EXCLI J. 2020; 19: 1533–1543.\n\nOrioli L, Servais T, Belkhir L, et al.: Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academic center in Belgium. Diabetes Metab. Syndr. 2021; 15(1): 149–157. PubMed Abstract | Publisher Full Text\n\nOrtega E, Corcoy R, Gratacòs M, et al.: Risk factors for severe outcomes in people with diabetes hospitalised for COVID-19: a cross-sectional database study. BMJ Open. 2021; 11(7): e051237. PubMed Abstract | Publisher Full Text\n\nPazoki M, Keykhaei M, Kafan S, et al.: Risk indicators associated with in-hospital mortality and severity in patients with diabetes mellitus and confirmed or clinically suspected COVID-19. J. Diabetes Metab. Disord. 2021; 20(1): 59–69. Publisher Full Text\n\nRaghavan A, Nanditha A, Satheesh K, et al.: Profile and prognosis of patients hospitalized for COVID-19 virus infection with and without diabetes - An observational study from South India. Diabetes Metab. Syndr. 2021; 15(4): 102143. Publisher Full Text\n\nRicchio M, Tassone B, Pelle MC, et al.: Characteristics, Management, and Outcomes of Elderly Patients with Diabetes in a Covid-19 Unit: Lessons Learned from a Pilot Study. Medicina (Kaunas). 2021; 57(4): 341. PubMed Abstract | Publisher Full Text\n\nSeiglie J, Platt J, Cromer SJ, et al.: Diabetes as a Risk Factor for Poor Early Outcomes in Patients Hospitalized With COVID-19. Diabetes Care. 2020; 43(12): 2938–2944. PubMed Abstract | Publisher Full Text\n\nShang J, Wang Q, Zhang H, et al.: The Relationship Between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China. Am. J. Med. 2021; 134(1): e6–e14. PubMed Abstract | Publisher Full Text\n\nShi Q, Zhang X, Jiang F, et al.: Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study. Diabetes Care. 2020; 43(7): 1382–1391. PubMed Abstract | Publisher Full Text\n\nWang X, Liu Z, Li J, et al.: Impacts of Type 2 Diabetes on Disease Severity, Therapeutic Effect, and Mortality of Patients With COVID-19. J. Clin. Endocrinol. Metab. 2020; 105(12): dgaa535. PubMed Abstract | Publisher Full Text\n\nWu D, Gao S: Analysis of the lymphocyte count in type 2 diabetic patients with coronavirus disease (COVID-19): A retrospective study in a centralized treatment center. Diabetes Res. Clin. Pract. 2020; 166: 108340. PubMed Abstract | Publisher Full Text\n\nWu J, Zhang J, Sun X, et al.: Influence of diabetes mellitus on the severity and fatality of SARS-CoV-2 (COVID-19) infection. Diabetes Obes. Metab. 2020; 22(10): 1907–1914. 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PubMed Abstract | Publisher Full Text\n\nZheng M, Wang X, Guo H, et al.: The Cytokine Profiles and Immune Response Are Increased in COVID-19 Patients with Type 2 Diabetes Mellitus. J. Diabetes Res. 2021; 2021: 1–8. Publisher Full Text\n\nConnors JM, Levy JH: COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020; 135(23): 2033–2040. PubMed Abstract | Publisher Full Text\n\nReview Manager (RevMan) [Computer program]. Version 5.4. The Cochrane Collaboration. 2020.\n\nMirza AF, Halim C, Sari MI: ‘The relationship of age, sex and prothrombin time related to the severity and mortality of COVID-19 patients with diabetes mellitus: a systematic review and meta analysis’, figshare. Dataset.2022. Publisher Full Text"
}
|
[
{
"id": "269067",
"date": "16 May 2024",
"name": "Fajri Marindra Siregar",
"expertise": [
"Reviewer Expertise biochemistry",
"health and 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\nThe author should properly clarify the search method utilised in each database, as each database has a unique search algorithm, so that other scholars can easily adapt it.\nNext, the author must certify that the results of the literature search are articles published until when?\nThe analysis of statistical results states that there is very high (significant) variability in each variable; has the author made any efforts to lessen this heterogeneity? (Please refer to https://handbook-5-1.cochrane.org/chapter_9/9_5_3_strategies_for_addressing_heterogeneity.htm)\nFurthermore, the conclusions presented are not in accordance with the results obtained by the author. In the conclusion the author stated \"Patients with older age with diabetes tend to have more severe disease than non-diabetics\" even though the meta-analysis carried out only compared age between the Covid group with DM vs without DM, there was no study of morbidity variables.\nLikewise, the statement \"Patients with diabetes who are hospitalized are more likely to be male, indicating that males are more susceptible to severe disease\" in our opinion is not appropriate considering that there are no variables for hospitalization status or degree of disease that were studied by the author in the meta-analysis section.\nFurthermore, considering that there are still several limitations that may not be avoidable, these need to be explored further by the author in the discussion section, such as the influence of disease onset and disease degree.\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? I cannot comment. A qualified statistician is required.\n\nAre the conclusions drawn adequately supported by the results presented in the review? No\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": "11651",
"date": "21 Jun 2024",
"name": "Mutiara Indah Sari",
"role": "Author Response",
"response": "Dear Reviewer, Thank you for the review. We will revise the manuscript based on your suggestions. 1: The author should properly clarify the search method utilised in each database, as each database has a unique search algorithm, so that other scholars can easily adapt it. Response: We will add more details on the search strategy such as the filters for each database in the text. 2: Next, the author must certify that the results of the literature search are articles published until when? Response: We will add the publication years for the included literatures in the text. 3: The analysis of statistical results states that there is very high (significant) variability in each variable; has the author made any efforts to lessen this heterogeneity? Response: Referring to the handbook, we performed point 1 (rechecking the data) and 7 (studies exclusion) to reduce heterogeneity. We will add brief information on this in the text. 4: Furthermore, the conclusions presented are not in accordance with the results obtained by the author. In the conclusion the author stated \"Patients with older age with diabetes tend to have more severe disease than non-diabetics\" even though the meta-analysis carried out only compared age between the Covid group with DM vs without DM, there was no study of morbidity variables. Likewise, the statement \"Patients with diabetes who are hospitalized are more likely to be male, indicating that males are more susceptible to severe disease\" in our opinion is not appropriate considering that there are no variables for hospitalization status or degree of disease that were studied by the author in the meta-analysis section. Response: It is true that our result is comparing COVID patients with vs without DM, so we will make changes on the conclusion and a few other parts of the text (for consistency and clarification) based on your suggestion. However, we would like to note that as DM is a comorbidity in COVID, we use it as an indicator of a more severe disease. 5: Furthermore, considering that there are still several limitations that may not be avoidable, these need to be explored further by the author in the discussion section, such as the influence of disease onset and disease degree. Response: We will add the limitations to the text as suggested. Sincerely, Mutiara Indah Sari"
}
]
}
] | 1
|
https://f1000research.com/articles/11-729
|
https://f1000research.com/articles/12-1599/v1
|
18 Dec 23
|
{
"type": "Research Article",
"title": "Adaption and psychometric evaluation of the Hindi version of Neck Disability Index in the rural population of Northern India: A cross cultural study",
"authors": [
"Mohammad Sidiq",
"Arunachalam Ramachandran",
"Balamurugan Janakiraman",
"Faizan Zaffar Kashoo",
"Aksh Chahal",
"Janvhi Singh",
"Yousef Almotairi",
"Abdul Aziz Almotairi",
"Mohammad Miraj",
"Sai Jaya Prakash CH",
"Krishna Reddy Vajrala",
"Ramprasad Muthukrishnan",
"Praveen Kumar Kandakurti",
"Mohammad Sidiq",
"Arunachalam Ramachandran",
"Balamurugan Janakiraman",
"Faizan Zaffar Kashoo",
"Aksh Chahal",
"Janvhi Singh",
"Yousef Almotairi",
"Abdul Aziz Almotairi",
"Mohammad Miraj",
"Sai Jaya Prakash CH",
"Krishna Reddy Vajrala",
"Ramprasad Muthukrishnan"
],
"abstract": "Background To ensure the validity and therapeutic utility of the Neck disability index (NDI) scale, translations, cultural adaptations and psychometric evidence is necessary. This study aimed to address the absence of a suitable and validated Hindi version of the NDI for the rural population. The specific objectives were to translate, adapt, and evaluate the psychometric properties of the newly developed Hindi version of the NDI.\n\nMethods Following guidelines provided by the American Association of Orthopedic Surgeons, the original English NDI scale was cross-culturally adapted into Hindi. The adaptation process included translations (forward and backward), expert committee review, pre-testing and cognitive debriefing with 30 individuals experiencing chronic non-specific neck pain. The outcome of this process was the creation of the Hindi version of the NDI, termed NDI-Hi. Subsequently, NDI-Hi was administered to 211 participants with neck pain from multiple centers for psychometric testing. The evaluation involved test-retest reliability over a 48-hour interval, factor analysis, assessment of internal reliability measures, and criterion-related validity by comparing it with the NPAD-Hindi version.\n\nResults The NDI-Hi version exhibited favorable psychometric properties, including good test-retest reliability with an intra-class correlation coefficient (ICC) of 0.87. Internal consistency of the scale was high, indicated by Cronbach’s alpha coefficient (α) of 0.96. The standard error of measurement (SEM) was determined to be 2.58, and the minimal detectable change (MDC) was calculated to be 7.15. Furthermore, the NDI-Hi showed significant correlation with the NPAD-Hindi version, with a correlation coefficient (rho) of 0.86, and a p-value of less than 0.001.\n\nConclusions The NDI-Hi demonstrated validity and reliability as an outcome tool for assessing neck disability. It can be effectively utilized in clinical practice and research settings involving Hindi-speaking individuals with chronic non-specific neck pain. The adapted scale is particularly well-suited for the rural Northern Indian Hindi-speaking population.",
"keywords": [
"Translation",
"Psychometric testing",
"Hindi",
"Neck pain",
"Neck disability index",
"Rural India"
],
"content": "Introduction\n\nNon-specific neck pain is characterized by lack of pathognomonic signs and symptoms (Bernal-Utrera et al., 2020) and neck pain is the second biggest contributor to the global disability-adjusted life years among musculoskeletal disorders (Blyth et al., 2019). Around 50% of adults experience neck pain annually, leading to a poorer quality of life (Safiri et al., 2017). Disability related to neck pain represent a substantial socioeconomic burden (e.g., health care utilization, work absenteeism, and lost productivity) (Manchikanti et al., 2009). In 2016, among the 154 conditions, low back and neck pain had the highest health-care spending in the United States estimated at USD 134.5 billion (Dieleman et al., 2020). In rural India, the average expenditure on healthcare per family in Indian rupees is INR 3,040.82 per month (O. Article, 2018), but musculoskeletal disorders are yet to be included in National Health Policy 2017 (Principles et al., n.d.). Most people living with non-specific neck pain reported experience of physical (e.g., pain and disability) and psychological (e.g., anxiety, depression, and fear avoidance beliefs) concerns (Simula et al., 2019). Patient-reported outcome measures (PROMs) are commonly used in research and clinical settings to report physical and psychological problems in individuals with neck pain (Wirth et al., 2016) (Lee et al., 2015). The NDI is a reliable, valid, and commonly used PROM to evaluate physical problems (pain and disability) among individuals with neck pain, which has been translated into many different languages like; Turkish (A. T. V. Study, 2008), Brazilian (Cook et al., 2006), Portuguese (Cook et al., 2006), German (Awaji, 2016), French, Swedish (though modified) (Lee et al., 2006), Korean (Song et al., 2010), Iranian (Mousavi et al., 2007), Dutch (Reneman, 2012), Greek (Trouli et al., 2008), Italian (Monticone et al., 2012), Arabic (Khair et al., 2020), Japanese (Nakamaru et al., 2012), Polish (Misterska et al., 2011), Thai, Punjabi (Sandal et al., 2021) and Marathi language (A. M. V. Study, 2015). Translating a widely used questionnaire allows comparisons of different populations, clinical trials to determine the functional ability of the population with neck pain in India and also permits comparison or exchange of findings beyond cultural and language barriers. Questionnaires meant to be used across cultures must be translated linguistically to improve understanding and adapted to the cultural context to maintain the content validity of the tool. Out of the total population of 1.3 billion Indians, about 0.322 billion native and 0.270 billion non-native speakers speak Hindi as per the National Census of India 2011 (Principles et al., n.d.).\n\nIn our extensive search, authors found one published work that aimed to translate, adapt and perform test-retest reliability, validity of the Hindi-version of NDI (Shakil et al., 2011), but the authors reported of not conducting the validity test due to feasibility constraints. We found that the authors of the previous version did not follow steps recommended or guidelines for the process of cross cultural adaptation of self-reported measures (Beaton et al., 2000) and most of the psychometric properties analysis, dimensionality factor analysis, responsiveness (MDC, Minimal Detectable Change) were are neither performed nor mentioned, living behind a methodological gap that has led to considerably decreased utility of Hindi-version of NDI in research and clinical set up. Further, there is compelling evidence from a review that this published work lacks methodological quality in the process of translation, which implies conduction of further research to develop a reliable, validated, and tested Hindi version of NDI. In addition, the previous version also has no mention of permission from the original author of the NDI tool (Pellicciari et al., 2016). To improve the inclusivity in clinical set up and research, it is important that the translation process, adaptation understanding the cultural norms, values and behaviors are prioritized. Further, it is mandate to follow as per the steps for recommended guidelines for the process of cross-cultural adaptation of self-reported measures and rigorous psychometric properties analysis as recommended by Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) (Mokkink et al., 2010).\n\nAs the occurrence of neck pain continues to rise, especially among native Hindi speakers, having a well-validated Hindi version of the NDI will enhance its clinical applicability and, most significantly, foster the inclusion of Hindi-speaking individuals suffering from neck pain in rural India but lacking proficiency in the English language. Therefore, this study intended to translate and adapt the original version of NDI into Hindi and assess its psychometric properties among the Hindi-speaking people with chronic non-specific neck pain (CNSNP). Furthermore, objectives include translating NDI into the Hindi language and testing the Hindi version of the NDI for its reliability and validity and responsiveness among patients with CNSNP.\n\n\nMethods\n\nThe present study is an observational cross-sectional study that involves two phases, the first phase includes the translation of the NDI and the second phase is where the psychometric properties were tested. The translation, adaptation, and psychometric testing of the Hindi version of NDI in this study was performed for the tool requirement of a future registered clinical trial among Hindi speaking rural North Indian population (Clinical Trials Registry of India, CTRI/2021/08/036040).\n\nThe study adhered to the SAGER guidelines for reporting sex and gender information. Sex and gender differences were not taken into consideration for the design of the study (Heidari et al., 2016).\n\nThis study was approved by the Institutional Review Board of the Madhav University, Rajasthan, (Ref. No: MU/IEC/21/14; dated 24/07/2021) and written informed consent for participation was obtained before patient recruitment. All procedures were conducted in accordance with the declaration of Helsinki. The purposes and the importance of the study were clarified to each participant. Participants were free to refuse to participate or answer any of the questions throughout the course of the study to ensure data confidentiality at all levels of the study, names of participants and any personal identifiers were not included. The permission to develop NDI-Hindi version was obtained from the author of the original version Professor Howard Vernon.\n\nThis study was conducted at the Physiotherapy outpatient department (OPD) of Sanskriti University Mathura, India and Jeevan Jyoti Hospital Mathura in the Northern State of India (Mathura city, Uttar Pradesh) from August 2021 to June 2022. Hence, the study protocol was presented to the Ethical member at the Madhav University and approval obtained. Further, the Ethical approval letter and the study proposal was submitted to the Clinical Trial Registry of India (Government of India) CTRI, which verified the application and granted permission to conduct the definitive study. The study settings are the associate centers of Madhav University, and proper permission was obtained from the two centers to conduct the study. A total of 220 participants with CNSNP were recruited across two centers, of which 211 participants (114 females and 97 males) completed all participant-reported socio-demographic data, clinical information using face to face interviews as the participants in general visit the study center for consultations and physical rehabilitation, hence we decided to use interview method to improve the quality of data collected. by trained assessors. Neck Disability Index – Hindi version (NDI-Hi) and Neck Pain and Disability Scale (NPAD) (Agarwal & Allison, 2006). This study followed recommendations of best practices for developing and validating scales (R. Article, 2017), which suggests at least 5-10 participants per item in the tool as recommended by the COSMIN checklist (Mokkink et al., 2010; Sidiq, 2023). A sample size of 220 subjects was considered to improve the accuracy of the findings. Both, men and women, aged 18 years old and above living with CNSNP > 3 months duration were included in the study. Individuals with acute neck pain, diseases causing neck disability, previous cervical spine injury, prolapsed intervertebral disc disease, traumatic vertebral fractures, neck surgery, clinically recognizable cognitive impairment, pregnancy and those who could not read and speak Hind were excluded from the study.\n\nNeck Disability Index (NDI)\n\nThe NDI, originally developed by Vernon and Mior (Vernon & Mior, 1991) is a 10-item or section patient-reported outcome measure designed to assess neck pain and pain-related disability. The tool consist of 10 sections designed to self-report on how neck pain impacts the activities of daily life, the domains are; intensity of pain, personal care (dressing, washing), lifting heavy and light weights, reading, headaches, concentration, work, driving, sleeping, and recreation. Each section consists of six activity-based exclusive responses expressing progressive levels of functional disability. Item scores range from 0 (no disability) to 5 (total disability) and Vernon also established categorization of scores as; 0 to 4 no disability, 5 to 14 mild disability, 15 to 24 moderate disability, 25 to 34 severe disability, and ≥ 35 complete disability. The total score is out of 50 (Vernon & Mior, 1991) and is also frequently normalized to 100 and reported as a percentage. The NDI (one-dimensional questionnaire) measures a single construct, and the questionnaire has demonstrated moderate differences in validity and reliability with a different patient population (Pietrobon et al., 2002).\n\nThe NDI© is protected by international copyright, with all rights reserved to Dr Howard Vernon. Do not use without permission. For information on, or permission to use the NDI©, please contact Mapi Research Trust at https://eprovide.mapi-trust.org. NDI © Dr Howard Vernon, 1991. All Rights Reserved. The users who do not receive specific funding for their use of the questionnaire can download the NDI© from ePROVIDE™, using the “online distribution” process.\n\nNeck Pain and Disability Scale (NPAD)\n\nThe NPAD scale is a 20-item multi-dimensional questionnaire designed to assess neck pain and disability. The items are scored along a 10 cm visual analog scale (VAS) with the scores ranging from 0 to 5 in VAS. A higher score indicates greater disability. The Hindi version of NPAD has been cross-culturally translated and validated among 64 Indian individuals with cervical radiculopathy. The Hindi version of NPAD has been psychometrically tested and shown to have acceptable internal consistency and validity (Agarwal & Allison, 2006).\n\nTool adaptation and translation was conducted as per the guidelines suggested by Beaton et al., 2000 (Beaton et al., 2000). The translation and adaptation process for NDI consists of the following steps; forward translation, synthesis, backward translation, expert committee review, and synthesis, tool pretesting, and submission and appraisal of the written reports by the translation-adaptation coordinating committee (Beaton et al., 2000). In step one, forward translation was performed from English to Hindi language by two Hindi native translators (a professional translator and a post-graduate employee working in education department) who were fluent in the English language. One independent translator was blinded to process of forward translation of NDI. This was done to make sure the equivalency from a therapeutic point of view rather than literal equivalence. The other translator was informed about the purpose of the study and the concepts being studied. This was for contemplating the language used by the population and spotlight terms in the original questionnaire, the translation of which might have been obscure. Two forward-translated documents (T1 and T2) were produced. In step two, the independently translated T1 & T2 documents were shared among the two translators to synthesize NDI-Hi (version 1). Any inconsistencies, differences in the concepts and/or meaning, elusive wordings were sorted by discussion and agreement. In step three, the first draft NDI-Hi was back-translated to English language by two bilingual independent translators (native Hindi language speaking teachers with master’s degree in English) and not familiar with the construct being assessed and blinded to the process of forward translation. After discussion and agreement between back translators and the principal investigator (MS), a third translation was performed. In step four, all three documents were presented to the expert panel for review and discussion. The expert committee was comprised of four translators, two review committee experts from the university and two senior physiotherapy academicians who reviewed the Hindi version of the questionnaire. The panel discussed clarity, relevance, modifications, comprehension and synthesized the pre-final version for field testing Figure 1.\n\nNDI, Neck disability index.\n\nIn step five, upon approval of the panel, NDI-Hi was piloted on 30 individuals with CNSNP (19 females and 11 males). A cognitive (qualitative) debriefing was conducted to evaluate the understanding, clarity, language, cultural appropriateness, and acceptability of the NDI-Hi. As a result, the majority of participants reported a good understanding of the tool. However, 16 participants reported section eight ‘driving’ not applicable to them. Based on cognitive debriefing comments made by the participants, the committee agreed to reword section eight (driving) to fit the cultural context in India where most people do not drive car, rather travel by public and/or private transport and motorbike. For the participants who did not answer/drive, the total score was adjusted from 45 instead of 50 (multiplying 50/45). The final Hindi version of the NDI was then compared with the original one to achieve representational, fact-finding and contextual equivalence.\n\nPsychometric properties were assessed using the final version of the NDI-Hindi (Sidiq, 2023) on 211 patients with CNSNP for > 3 months duration across three centers. The test-retest reliability of the NDI-Hi version was determined by calculating Cronbach’s alpha with an alpha value of > 0.7 (deemed acceptable), > 0.8 (considered good), and > 0.9 (considered excellent) to grade the internal consistency (Taber, 2018). The minimum sample size required for two-tailed Cronbach’s alpha test was calculated using the Bonet formula based on assumptions; item in the scale (k) 10, power 0.90 (1 - β), type I error (α) 0.05, value of Cronbach’s alpha at null hypothesis (CA0) and expected value of Cronbach’s alpha (CA1) were identified at 0.0 and 0.8, respectively (Bonett, 2002). The required sample size was 70. NDI-Hi was re-administered on about 50% of the participants (n = 110) at the interval of 48 hours to assess its test-retest reliability. This is more than the power calculated sample.\n\nTo determine the dimensionality of the NDI-Hi, a stepwise exploratory factor analysis (EFA) was performed with Kaiser Meyer Olkin and Bartlett’s criteria with a retention rule of an Eigenvalue > 1 (items with loadings ≥ 0.4 were considered satisfactory). Independent factors were obtained with maximum likelihood using the Varimax rotation model. The floor and ceiling effects, distribution and completeness of items responses and missing values were examined for content validity. The concurrent validity method was used for the criterion-related validity; Pearson’s correlation analysis was done to establish relation between NDI-Hi and Visual Analogue Scale (VAS). The convergent construct validity was examined by comparing the NDI-Hi and Hindi version of NPAD using Spearman rank correlation coefficient (r). The r value of > 0.80 were considered excellent, and 0.61 to 0.80 very good. It is expected that the Hindi versions of NDI and NPAD would have moderate correlations since both tools measures the impact of neck pain on the functional status of the patients (Agarwal et al., 2006). Standard error of measurement (SEM) was calculated from the square root (SEM = SD √ (1-R)) of the within-subject variance from ANOVA for random-effect to evaluate the measurement error. MDC95% was derived using the SEM to allow expression of the smallest magnitude of change that reveals the true change rather than measurement error by using the formula MDC95% = 1.96 √2x SEM or 2.7*SEM. The Bland-Altman plot was also used to determine agreement (Bland & Giavarina, 2015) (Figure 2).\n\nBold blue line representing the mean of difference, the red lines representing 95% LOA and the grey lines representing the 95% CI of the mean of the difference. NDI-Hi, Hindi-version of the Neck disability index; LOA, limits of agreement.\n\nIBM SPSS Statistics (RRID: SCR_016479) version 20 was used to analyze the data (SPSS 20, IBM, Armonk, NY, USA). Characteristics and observations of the quantitative and qualitative variables were summed using the mean, standard deviation (SD) and frequencies or relative frequencies. Normality of scores from different instruments was examined using one-sample Kolmogorov-Smirnov test. Internal consistency, test-retest reliability, and convergent validity of the two scales used in the analysis were examined. Authors in the present study were able to determine the internal consistency of the NDI-Hindi using Cronbach’s alpha index with values between 0.70 and 0.90 considered satisfactory. For test-retest reliability, interclass correlation coefficients (ICCs) and 95 percent confidence intervals (CIs) were determined. ICCs below 0.40 were considered low, those in the range of 0.4-0.70 were considered moderate, 0.70-0.90 were considered significant and values above 0.9 were considered exceptional respectively. The degree of correlation between NDI-Hindi and the NPAD at baseline was determined using Spearman’s rho correlation. The significance level was set at P < 0.05. According to the sex and Gender Equity in research (SAGER) guidelines, data analysis of sex/gender differences and/or similarities were performed.\n\n\nResults\n\nDemographic variables of the participants have been tabulated in Table 1 (Sidiq et al., 2023). All participants were assessed for their body mass index, duration of neck pain, pain medication, associated medical condition, marital status, employment status, level of education, income and mean and SD scores of NDI and NPAD. The majority of participants were female (n = 149, 70.6%), married (n = 152, 72.0%) and unemployed (n = 120, 56.9%).\n\nTable 2 displays the mean scores extracted from the participants in 10 sections of the NDI-Hindi. Participants were moderately affected due to neck disorder and the mean rating on NDI was 32.02 (6.9) out of 50 in total. Principle component analysis revealed two-factor structures (physical dysfunction and neurological dysfunction) of NDI-Hindi. The physical dysfunction included pain intensity personal care, lifting, work, driving, reading and recreation were moderately to severely affected with a mean score ranging from 3.36-3.92, while neurological dysfunction that included headaches, concentration and sleeping were mildly affected with mean scores 2.3 and standard deviation of 0.6.\n\n* Indicates <0.05.\n\n** Indicates <0.01.\n\nThe Cronbach’s alpha reliability was 0.962, which indicated that respondents were able to read and comprehend the 10 NDI-Hindi items well. However, all 10 indicators demonstrated a meaningful adjusted total association with their total scores. When these indicators were removed from the total, all of the items exhibited a corrected item-total correlation greater than 0.75, showing reasonably substantial shared covariance (Table 2).\n\nTest-retest reliability was assessed seven days after the initial assessment and was found to be excellent. The test-retest reliability was excellent for the overall NDI-Hindi and average Interclass correlation coefficient (ICC) was 0.893, with a 95% Confidence interval (CI) (0.795, 0.937) (p < 0.001) (Table 2). The mean of item variances was 0.648, with inter-item covariance’s mean of 0.465 (Table 3).\n\nConstruct validity of the NDI-Hindi was estimated using principal component analysis (factor analysis) with varimax rotation (Table 4). Data met the assumptions (Kaiser–Meyer Olkin = 0.826) of sample adequacy and Bartlett’s test of sphericity. The total variance explained by two factors was 87.5%. The analysis found a two factor structure of scale; Factor 1 included the first seven items of the questionnaire (77.3% of variance), Factor 2 included three items (10.2% of variance) (Table 5). Factor loading was determined using a scree plot (Figure 3).\n\n** Correlation is significant at the 0.01 level (2-tailed).\n\n* Correlation is significant at the 0.05 level (2-tailed).\n\nNDI-Hi, Hindi-version of the Neck disability index.\n\nThe scores of NDI-Hindi showed excellent correlation with the total scores on Hindi-validated version of NPAD scale. Scores on neck pain and disability scale showed a significant positive correlation with all 10 items of NDI, with the highest correlation with lifting item (0.917, p = 001) and a least but significant correlation with the concentration item and sleeping (0.845, p = 0.001) (Table 6).\n\n** Correlation is significant at the 0.01 level (2-tailed).\n\n* Correlation is significant at the 0.05 level (2-tailed).\n\n\nDiscussion\n\nThis study aimed to translate and adapt the original English version of NDI into the national language of India (Hindi) and test the psychometric properties of the NDI-Hi version. The recommended guidelines were followed during translation and adaptations (Beaton et al., 2000). The translation, adaptation, and synthesis of NDI-Hi was easy and accepted by the Hindi speaking people with CNSNP. Overall findings from this study indicate NDI-Hi to be a reliable and valid patient-reported outcome measure that could be used by researchers and clinicians to assess disability and functional limitations caused by neck pain among the Hindi-speaking population who are unable to read or write in the English language.\n\nNDI-Hi demonstrated excellent internal consistency and Cronbach α of 0.89, which is comparable to the reports of previous works (0.74–0.97) and explains sample adequacy (Wu et al., 2010). In this study, the time interval for the test-retest re-administration was set at 48 hours, a duration that is likely to result in minimal alterations in the patient’s clinical condition and minimal memory-related effects. Likewise, NDI-Hi also showed good internal consistency, indicating good reliability. The acceptability of the NDI-Hi showed that all the items were below the threshold recommended for floor effects (20%). However, the ceiling effect of the pain intensity was found to be marginally (21.6%) higher than the threshold recommended. Similarly, previous studies reported no floor or ceiling effects with the only exception being the intensity of pain (Nakamaru et al., 2012; Shashua et al., 2016; Trouli et al., 2008; Farooq et al., 2017). Though this phenomenon is not unique, a study on the Malay version of NDI reported moderate responsiveness of pain intensity and also explains the complexity in quantifying pain (Lim et al., 2020).\n\nIn our study, the pilot test conducted to check the feasibility and acceptability of the translated NDI-Hi version found that the majority of participants were not responding to the item on driving and the same was discussed in the cognitive debriefing. In India, the majority of individuals travel using motorbikes, public transportation, and private vehicles, with a relatively small portion choosing to commute by car. Moreover, when section eight, which pertains to driving, is culturally adapted to encompass driving, riding, or traveling, it significantly enhances the responses to this section, reducing the occurrence of missing values related to driving in various studies (Cook et al., 2006; Lee et al., 2006). SEM (< 0.4) and MDC95% of the NDI-Hi version indicated an absolute reliability and genuine agreement of repeated measurements, and suitability of NDI-Hi for clinical and research uses. MDC95% of 7.15 (score range 0-50) will guide clinicians and researchers of true change in NDI-Hi scores. Scores at or above MDC value indicate meaningful clinical change in patients. MDC value of NDI-Hi is comparable to the values reported by other researchers and smaller (precise) than other studies (Pool et al., 2007; Young et al., 2009; Trouli et al., 2008; Farooq et al., 2017; Maki et al., 2014; Shashua et al., 2016). The smallest detectable change (SDC) and minimally important difference (MIC) reported by the Dutch version was 11.5, and 31.7 respectively, the Italian version NDI showed MIC of 10, and a methodological review conducted including 19 NDI versions reported only these three versions of NDI mentioned MIC (Yao et al., 2019). The MDC reported in this study is 7.15, which is relatively lower than MDC reported elsewhere, and this is suggestive that even a smaller change in the Hindi version of NDI shall be considered as an important yardstick of clinical relevant hence, offers a sensitive outcome tool even in case of less powered sample or individual level studies.\n\nThe validity of NDI-Hi was conducted by qualitative cognitive debriefing to establish content validity and correlation test of the scale with the NPAD Hindi version to evaluate the construct convergent validity (Brod et al., 2009). Based on the pilot study and cognitive briefing, rewording of item eight was done, which improved the understanding, acceptance and response rate. Factor analyses resulted in a hypothesized 2-factor solution for NDI-Hi represented as physical dysfunctions and neurological dysfunctions. These factors explained 69.51% of the total variance, and the variance reported was comparable to some previous studies (Nakamaru et al., 2012). The Hindi versions of NDI and NDAP appear to measure a similar construct. The NDI is a condition-specific patient-reported outcome measure (PROM) and it is frequently used in researches exploring intervention efficacy among individuals with neck pain. Similarly, psychometric properties of NDI-Hi propose it as a suitable PROM for Hindi-speaking individuals with neck pain. Nonetheless, suitability of NDI in patients with whiplash injury, social and emotional is questioned by Hoving et al., highlighting limitation of the NDI that lacks elements to address these problems (Hoving et al., 2003).\n\nThis study recruited samples beyond the recommended guidelines for cross-cultural adaptations of outcome measures and the required power calculated sample for test-retest reliability, which improved the statistical power of the psychometric evaluation of the NDI-HI version. However, there are few limitations to mention; this study is a cross-sectional design and hence any correlations should not be interpreted as causal effects. This study used only a self-reported questionnaire, the relationship between the activity limitations of neck pain (NDI) and physical tests were not considered and the study was done among rural northern Indian population only.\n\n\nConclusions\n\nThe English version of NDI was successfully adapted to suit the rural Indian cultural context and translated to the Hindi-India version. The Hindi version of the NDI-Hi tool has healthy psychometric properties and appears to be suitable for use in epidemiological studies and clinical trials among Hindi language speakers.",
"appendix": "Data availability\n\nFigshare: NDI DATA SET. https://doi.org/10.6084/m9.figshare.24354952 (Sidiq et al., 2023).\n\nFigshare: COSMIN checklist for ‘Adaption and psychometric evaluation of the Hindi version of Neck Disability Index in the rural population of Northern India: a cross cultural study’. https://doi.org/10.6084/m9.figshare.24126609 (Sidiq, 2023).\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 Dr. Howard Vernon for granting permission to use and culturally adapt to the rural Indian population and assisting to translate the Neck Disability Index into Hindi-India version. Our gratitude and appreciation to all the data collectors and participants of this study.\n\n\nReferences\n\nAgarwal S, Allison GT: Reliability and validity of the Hindi version of the Neck Pain and Disability Scale in cervical radiculopathy patients.2006. June 2014. 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Publisher Full Text\n\nCook C, Richardson JK, Braga L, et al.: Cross-cultural adaptation and validation of the Brazilian Portuguese version of the Neck Disability Index and Neck Pain and Disability Scale. Spine. 2006; 31(14): 1621–1627. PubMed Abstract | Publisher Full Text\n\nDieleman JL, Cao J, Chapin A, et al.: US Health Care Spending by Payer and Health Condition, 1996-2016. JAMA. 2020; 323(9): 863–884. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFarooq MN, Mohseni-Bandpei MA, Gilani SA, et al.: Urdu version of the neck disability index: A reliability and validity study. BMC Musculoskelet. Disord. 2017; 18(1): 1–11. 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. Res. Integr. Peer Rev. 2016; 1(1): 1–9. Publisher Full Text\n\nHoving JL, O’Leary EF, Niere KR, et al.: Validity of the neck disability index, Northwick Park neck pain questionnaire, and problem elicitation technique for measuring disability associated with whiplash-associated disorders. Pain. 2003; 102(3): 273–281. PubMed Abstract | Publisher Full Text\n\nKhair U, Shahid W, Arshad N, et al.: Prevalence of nonspecific neck pain in dental practitioners of Lahore: A cross Prevalence of nonspecific neck pain in dental practitioners of Lahore: A cross sectional study.2020 May.\n\nLee H, Nicholson LL, Adams RD, et al.: Development and psychometric testing of Korean language versions of 4 neck pain and disability questionnaires. Spine. 2006; 31(16): 1841–1845. PubMed Abstract | Publisher Full Text\n\nLee H, Hübscher M, Moseley GL, et al.: How does pain lead to disability? A systematic review and meta-analysis of mediation studies in people with back and neck pain. Pain. 2015; 156: 988–997. PubMed Abstract | Publisher Full Text\n\nLim HHR, Tan ST, Tang ZY, et al.: Cross-cultural adaptation and psychometric evaluation of the Malay version of the Neck Disability Index. Disabil. Rehabil. 2020; 1–7. Publisher Full Text\n\nMaki D, Rajab E, Watson PJ, et al.: Cross-cultural translation, adaptation, and psychometric testing of the Roland-Morris Disability Questionnaire into modern standard Arabic. Spine. 2014; 39(25): E1537–E1544. PubMed Abstract | Publisher Full Text\n\nManchikanti L, Singh V, Datta S, et al.: Comprehensive review of epidemiology, scope, and impact of spinal pain. Pain Physician. 2009; 12(4): E35–E70. PubMed Abstract | Publisher Full Text\n\nMisterska E, Jankowski R, Glowacki M: Cross-cultural adaptation of the Neck Disability Index and Copenhagen Neck Functional Disability Scale for patients with neck pain due to degenerative and discopathic disorders. Psychometric properties of the Polish versions. BMC Musculoskelet. Disord. 2011; 12(1): 84. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMokkink LB, Terwee CB, Knol DL, et al.: The COSMIN checklist for evaluating the methodological quality of studies on measurement properties: A clarification of its content.2010.\n\nMonticone M, Ferrante S, Vernon H, et al.: Development of the Italian Version of the Neck Disability Index.2012; 37(17). Publisher Full Text\n\nMousavi SJ, Parnianpour M, Montazeri A, et al.: Translation and Validation Study of the Iranian Versions of the Neck Disability Index and the Neck Pain and Disability Scale. Spine. 2007; 32(26): 825–831. PubMed Abstract | Publisher Full Text\n\nNakamaru K, Vernon H, Aizawa J, et al.: Crosscultural adaptation, reliability, and validity of the Japanese version of the Neck Disability Index. Spine. 2012; 37(21): E1343–E1347. PubMed Abstract | Publisher Full Text\n\nPellicciari L, Bonetti F, Di Foggia D, et al.: Patient-reported outcome measures for non-specific neck pain validated in the Italian-language: a systematic review. Arch. Physiother. 2016; 6(1): 9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPietrobon R, Coeytaux RR, Carey TS, et al.: Standard scales for measurement of functional outcome for cervical pain or dysfunction: A systematic review. Spine. 2002; 27(5): 515–522. Publisher Full Text\n\nPool JJM, Ostelo RWJG, Hoving JL, et al.: Minimal clinically important change of the neck disability index and the numerical rating scale for patients with neck pain. Spine. 2007; 32(26): 3047–3051. Publisher Full Text\n\nPrinciples KP, Goals SQ, Thrust P, et al.: NATIONAL HEALTH POLICY. n.d.; 2017.\n\nReneman MF: Neck Pain and Disability Scale and Neck Disability Index: validity of Dutch language versions.2012; 93–100. Publisher Full Text\n\nSafiri S, Kolahi A, Hoy D, et al.: Global, regional, and national burden of neck pain in the general population, 1990-2017: systematic analysis of the Global Burden of Disease Study 2017. BMJ. 2017; 368. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSandal D, Jindal R, Gupta S, et al.: Reliability and Validity of Cross Culturally Adapted Punjabi Version of NDI (NDI-P) in Patients with Neck Pain: A Psychometric Analysis. Indian J. Orthop. 2021; 55(4): 918–924. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShakil H, Khan SA, Thakur PC: Test retest reliability and validity of Hindi version of Neck Disability Index in patients with neck pain. Indian J. Physiother. Occup. Ther. 2011; 5: 167–169.\n\nShashua A, Geva Y, Levran I: Translation, validation, and crosscultural adaptation of the Hebrew version of the neck disability index. Spine. 2016; 41(12): 1036–1040. PubMed Abstract | Publisher Full Text\n\nSidiq M, Janakiraman B, Chahal A, et al.: NDI DATA SET. [Dataset]. figshare. 2023. Publisher Full Text\n\nSidiq M: COSMIN checklist (COnsensus-based Standards for the selection of health Measurement INstruments). [Dataset]. figshare. 2023. Publisher Full Text\n\nSimula AS, Jenkins HJ, Holopainen R, et al.: Transcultural adaption and preliminary evaluation of “understanding low back pain” patient education booklet. BMC Health Serv. Res. 2019; 19(1): 1010–1011. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSong K, Choi B, Choi B: Cross-Cultural Adaptation and Validation of the Korean Version of the Neck Disability Index. Spine. 2010; 35(20): 1045–1049. PubMed Abstract | Publisher Full Text\n\nStudy, A. M. V: Cultural Adaptation, Reliability, and Validity of Neck Disability Index in Indian Rural Population. Spine. 2015; 40(2). Publisher Full Text\n\nStudy, A. T. V: The Cultural Adaptation, Reliability and Validity of Neck Disability Index in Patients With Neck Pain. Spine. 2008; 33(11): 362–365. PubMed Abstract | Publisher Full Text\n\nTaber KS: The Use of Cronbach’s Alpha When Developing and Reporting Research Instruments in Science Education. Res. Sci. Educ. 2018; 48(6): 1273–1296. Publisher Full Text\n\nTrouli MN, Vernon HT, Kakavelakis KN, et al.: Translation of the Neck Disability Index and validation of the Greek version in a sample of neck pain patients. BMC Musculoskelet. Disord. 2008; 9: 1–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVernon H, Mior S: The Neck Disability Index: a study of reliability and validity. J. Manip. Physiol. Ther. 1991; 14(7): 409–415.\n\nWirth B, Humphreys BK, Peterson C: Importance of psychological factors for the recovery from a first episode of acute non-specific neck pain - a longitudinal observational study. Chiropr. Man. Therap. 2016; 24(1): 9–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWu S, Ma C, Mai M, et al.: Translation and validation study of Chinese versions of the neck disability index and the neck pain and disability scale. Spine. 2010; 35(16): 1575–1579. PubMed Abstract | Publisher Full Text\n\nYao M, Xu B, Tian Z, et al.: PT US CR. Spine J. 2019. Publisher Full Text\n\nYoung BA, Walker MJ, Strunce JB, et al.: Responsiveness of the Neck Disability Index in patients with mechanical neck disorders. Spine J. 2009; 9(10): 802–808. Publisher Full Text"
}
|
[
{
"id": "291968",
"date": "05 Jul 2024",
"name": "Prem Venkatesan",
"expertise": [
"Reviewer Expertise My area of expertise is musculoskeletal pain and cardiopulmonary 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\nDear Editor, Thank you for providing me the opportunity to review the manuscript titled: “Adaption and psychometric evaluation of the Hindi version of Neck Disability Index in the rural population of Northern India: A cross cultural study”\nI have a few concerns about this manuscript: Abstract\nThe background of the study is not convincing enough, this can be written in a more acceptable way The different sample sizes used in the manuscript are absent in the methods section.\nIntroduction\nThe introduction contains a good number of facts and findings, but it looks jumbled up and it doesn’t properly lead to the need for the study. This can be improved by properly articulating the facts. Reference Princpal et al.m is wrongly cited.\nMethods\nThis study is mentioned as a cross-cultural study that has studied the adoption and psychometric evaluation of the NDI scale, But it is mentioned as an observational study. This has to be cross-checked as cross-cultural studies are not purely observational studies and adoption and psychometric evaluations are mostly methodological studies. This has to be clarified. How was the sample size estimated? Figure 1: Incomplete The data was collected from the subjects after 48 hours, and some justification was given in the discussion. Please provide the evidence for this. Has any evidence suggested that collecting data in 48 hours can give a better outcome? If yes please do justify it in the methodology section also. The sample size to be used for psychometric evaluation and test-retest reliability has to be similar. However, there is a disparity between the numbers used. What is the justification for the change in sample size? It was mentioned that the gender-specific analysis was done. I couldn’t find any analysis. What was the purpose of the pilot study?\nResults\nPlease align the tables corresponding to the findings. The current presentation makes it tough to correlate the findings.\nDiscussion\nThe discussion can be made better by stressing the findings. This study was done on the shortcomings of the previous study. When the primary aim of this study was to address the shortcomings, the results can also be specific to those. This study has only reported internal consistency and validity, but the aim of the study was not at all discussed with facts and findings.\nReferences\nTwo studies with the author name “Study” are wrongly cited.\nGeneral Comments\nThe manuscript needs language editing and grammatical correction. There is a lack of coherence and cohesion throughout the text.\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": "12033",
"date": "08 Aug 2024",
"name": "Dr Mohammad Sidiq",
"role": "Author Response",
"response": "Dear Editor, We express our sincere appreciation to the editor for the time and interest in this study. Dear reviewers, We appreciate and thank you for the valuable comments, suggestions, and interest in this research paper. We have amended the corrections according to the comments and suggestions provided. In addition, Spelling, grammar, and sentence structure errors have been corrected and the manuscript is revised based on the journal style requirements. All the authors agreed on the changes made in response to the reviewer's comments. Please find our responses below: With regards, Dr Mohammad Sidiq Reviewer 1 comment Abstract The background of the study is not convincing enough, this can be written in a more acceptable way. The different sample sizes used in the manuscript are absent in the methods section. Authors’ response Thank you, the changes are amended in the background section accordingly. We recruited n = 30 individuals for cognitive debriefing & n = 211 for the psychometric testing. Both samples are now mentioned in methods section of abstract (lines 43 - 44) and manuscript (methods-participant sub-section – lines 146-147). (Methods, Inclusion and exclusion criteria-Subsection; lines 156 -164). Reviewer 1 comment Introduction The introduction contains a good number of facts and findings, but it looks jumbled up and it doesn’t properly lead to the need for the study. This can be improved by properly articulating the facts. Reference Princpal et al.m is wrongly cited. Authors’ response The changes are now amended in the introduction section to improve the cohesion and lead towards the need for the study. (Introduction section, page 4 lines 89 – 95, lines 120 -126) The reference is now modified accordingly. Reviewer 1 comment Methods This study is mentioned as a cross-cultural study that has studied the adoption and psychometric evaluation of the NDI scale, But it is mentioned as an observational study. This has to be cross-checked as cross-cultural studies are not purely observational studies and adoption and psychometric evaluations are mostly methodological studies. This has to be clarified. How was the sample size estimated? Figure 1: Incomplete The data was collected from the subjects after 48 hours, and some justification was given in the discussion. Please provide the evidence for this. Has any evidence suggested that collecting data in 48 hours can give a better outcome? If yes please do justify it in the methodology section also. The sample size to be used for psychometric evaluation and test-retest reliability has to be similar. However, there is a disparity between the numbers used. What is the justification for the change in sample size? It was mentioned that the gender-specific analysis was done. I couldn’t find any analysis. What was the purpose of the pilot study? Authors’ response Thank you, as per the suggestion we have removed the observational study design. And amended changes related to the methods used (methods, lines 135-136). Considering the lack of specific guidelines and different authors used different formula to estimate sample size like; factor analysis formula, Kaiser-Meyer-Olkin sampling adequacy (values ranging from 0.50 to 0.60), regression formula and item-sample ratio estimation We intended to include all eligible patients with CNSNP attending both the study center’s during the study period to improve the statistical estimations and consistency of the results. (Methods section, lines 165 -171). A total of 220 respondent consented and 9 participants either did not complete the questionnaire or the data sheet was not complete. The figure 1 is changed now accordingly Thank you for the suggestion, we have amended the changes accordingly (Methods section; lines 262 -265) “test-retest re-administration was set at 48 hours, which is a minimum duration that is likely to result in minimal alterations in the patient's clinical condit110ion and minimal memory-related effects(Marx et al., 2003).Yes, considering the difficulty and constraints (response rate) in inviting the respondents to attend face to face interview prospectively for the 2nd time, we used the recommended “minimum sample size required for two-tailed Cronbach’s alpha test was calculated using the Bonet formula based on assumptions” . Hence, test-retest was conducted using n = 110. The same was prospectively informed and approved by the MAPI Research Trust. Thank you for pointing out, we have removed the statement now. The purpose of Pilot study and cognitive debriefing is now mentioned in the method section (lines 235 -242). Reviewer 1 comment Results Please align the tables corresponding to the findings. The current presentation makes it tough to correlate the findings. Authors’ response Changes done accordingly, thank you Reviewer 1 comment Discussion The discussion can be made better by stressing the findings. This study was done on the shortcomings of the previous study. When the primary aim of this study was to address the shortcomings, the results can also be specific to those. This study has only reported internal consistency and validity, but the aim of the study was not at all discussed with facts and findings. Authors’ response Yes, thank you for reminding us of our primary purpose of addressing the methodological gap of previous work. We have now amended the changes and added content according to your valid suggestions. (Discussion section, lines 353 – 364) “it is important to the commonly used NDI raw score is not linear and should likely not be used in interpretation. Hence, it is recommended to transform the raw NDI score into a linear measure (convert to 100) prior to data analysis. The lack of methodologies related to score transformations, hypothesis tested, dimensionality, and testing of validity in the previous work did not permit a meaningful comparison with findings of this study”. Reference; Hung M, Cheng C, Hon SD, Franklin JD, Lawrence BD, et al. Challenging the norm: further psychometric investigation of the Neck Disability Index. Spine J. 2015. doi:10.1016/j.spinee.2014.03.027. And, the same is mentioned as well. Please suggest us if the content added is justifying. Thank you again for pointing out. Reviewer 1 comment References Two studies with the author name “Study” are wrongly cited. Authors’ response Done accordingly"
}
]
},
{
"id": "291969",
"date": "11 Jul 2024",
"name": "Y. Ravi shankar Reddy",
"expertise": [
"Reviewer Expertise Rehabilitation",
"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\nReviewer's Report\nTitle: Adaption and Psychometric Evaluation of the Hindi Version of Neck Disability Index in the Rural Population of Northern India: A Cross-Cultural Study\n\nAbstract: The abstract provides a succinct overview of the study. However, it can be improved by adding more specific details to give readers a clearer understanding of the study's significance and outcomes. The background should specify the importance of validating the NDI for rural Hindi-speaking populations and how this fills a gap in current research. The methods section should detail the translation process more concisely, emphasizing the steps involved. The results section should highlight key statistics like the ICC, Cronbach's alpha, SEM, MDC, and correlation coefficients. Finally, the conclusions should reinforce the clinical applicability and importance of the NDI-Hi in rural settings.\n\nIntroduction: The introduction effectively outlines the prevalence and impact of non-specific neck pain globally and in India, providing a solid rationale for the study. To enhance it further, include more recent statistics and studies to underscore the growing burden of neck pain. Highlight the unique challenges faced by rural populations in India, such as limited access to healthcare and language barriers. Additionally, the introduction should emphasize the importance of culturally adapting the NDI to ensure its relevance and accuracy for Hindi-speaking patients. This sets a clear context for the need for the NDI-Hi and its potential benefits.\n\nMethods: The methods section is comprehensive, detailing the translation and adaptation process meticulously. To improve clarity, consider breaking down the translation steps into sub-sections with clear headings for each stage: forward translation, synthesis, backward translation, expert committee review, and pilot testing. This would make the process easier to follow. The section on psychometric testing should provide more detail on the statistical methods used, such as the criteria for factor analysis and the rationale for the selected time intervals for test-retest reliability. Including a flowchart summarizing the entire process could also enhance clarity and readability.\n\nResults: The results section presents the findings effectively, with detailed statistical analysis. To make it more impactful, provide more context for the statistical figures, explaining what they mean in practical terms. For instance, elaborate on how the high Cronbach’s alpha and ICC values demonstrate the reliability and validity of the NDI-Hi. Include more descriptive statistics and graphical representations, such as bar charts or histograms, to visually summarize the data. Additionally, the demographic characteristics of the participants should be discussed in relation to the findings, highlighting any significant correlations or trends.\n\nDiscussion: The discussion appropriately interprets the results, linking them back to the study's objectives and existing literature. To deepen the analysis, compare the psychometric properties of the NDI-Hi with those of other versions used in different cultural contexts. Discuss any unexpected findings or limitations encountered during the study, such as the challenges related to the driving item. Propose potential solutions or areas for future research to address these limitations. Furthermore, emphasize the clinical implications of the NDI-Hi, particularly how it can improve patient outcomes and research quality in rural Hindi-speaking populations.\n\nConclusion: The conclusion succinctly summarizes the study's findings and their significance. To enhance it, reiterate the key strengths of the NDI-Hi, such as its high reliability and validity. Highlight the broader impact of having a validated Hindi version of the NDI, such as its potential to inform public health policies and improve clinical practices in rural India. Additionally, suggest specific applications of the NDI-Hi in both clinical and research settings, emphasizing its role in enhancing the understanding and management of neck pain among Hindi-speaking populations.\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? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12034",
"date": "08 Aug 2024",
"name": "Dr Mohammad Sidiq",
"role": "Author Response",
"response": "Dear Editor, We express our sincere appreciation to the editor for the time and interest in this study. Dear reviewers, We appreciate and thank you for the valuable comments, suggestions, and interest in this research paper. We have amended the corrections according to the comments and suggestions provided. In addition, Spelling, grammar, and sentence structure errors have been corrected and the manuscript is revised based on the journal style requirements. All the authors agreed on the changes made in response to the reviewer's comments. Please find our responses below: With regards, Dr Mohammad Sidiq Reviewer 2 comment Abstract: The abstract provides a succinct overview of the study. However, it can be improved by adding more specific details to give readers a clearer understanding of the study's significance and outcomes. Authors’ response The background section of the abstract is revised accordingly. Reviewer 2 comment The background should specify the importance of validating the NDI for rural Hindi-speaking populations and how this fills a gap in current research. The methods section should detail the translation process more concisely, emphasizing the steps involved. The results section should highlight key statistics like the ICC, Cronbach's alpha, SEM, MDC, and correlation coefficients. Finally, the conclusions should reinforce the clinical applicability and importance of the NDI-Hi in rural settings. Authors’ response Thank you, the changes are made according to the suggestions Reviewer 2 comment Introduction: The introduction effectively outlines the prevalence and impact of non-specific neck pain globally and in India, providing a solid rationale for the study. To enhance it further, include more recent statistics and studies to underscore the growing burden of neck pain. Highlight the unique challenges faced by rural populations in India, such as limited access to healthcare and language barriers. Additionally, the introduction should emphasize the importance of culturally adapting the NDI to ensure its relevance and accuracy for Hindi-speaking patients. This sets a clear context for the need for the NDI-Hi and its potential benefits. Authors’ response Thank you, amendments related to language barriers, and the need for a clear context related outcome measures is emphasized. Reviewer 2 comment Methods: The methods section is comprehensive, detailing the translation and adaptation process meticulously. To improve clarity, consider breaking down the translation steps into sub-sections with clear headings for each stage: forward translation, synthesis, backward translation, expert committee review, and pilot testing. This would make the process easier to follow. The section on psychometric testing should provide more detail on the statistical methods used, such as the criteria for factor analysis and the rationale for the selected time intervals for test-retest reliability. Including a flowchart summarizing the entire process could also enhance clarity and readability. Authors’ response Thank you, we have included a new figure 1 based on the suggestions- to clearly explain the steps into sub-sections. The rationale for using 48 hours interval for test retest reliability is now included with reference and a new flowchart added (figure 1). Details regarding factor analysis is now added under the statistical analysis section. Reviewer 2 comment Results: The results section presents the findings effectively, with detailed statistical analysis. To make it more impactful, provide more context for the statistical figures, explaining what they mean in practical terms. For instance, elaborate on how the high Cronbach’s alpha and ICC values demonstrate the reliability and validity of the NDI-Hi. Include more descriptive statistics and graphical representations, such as bar charts or histograms, to visually summarize the data. Additionally, the demographic characteristics of the participants should be discussed in relation to the findings, highlighting any significant correlations or trends. Authors’ response We have added contents to explain the significance of findings. Reviewer 2 comment Discussion: The discussion appropriately interprets the results, linking them back to the study's objectives and existing literature. To deepen the analysis, compare the psychometric properties of the NDI-Hi with those of other versions used in different cultural contexts. Discuss any unexpected findings or limitations encountered during the study, such as the challenges related to the driving item. Propose potential solutions or areas for future research to address these limitations. Furthermore, emphasize the clinical implications of the NDI-Hi, particularly how it can improve patient outcomes and research quality in rural Hindi-speaking populations. Authors’ response We have now included statements related to the previous version of NDI and clinical implication related contents in discussion section. Reviewer 2 comment Conclusion: The conclusion succinctly summarizes the study's findings and their significance. To enhance it, reiterate the key strengths of the NDI-Hi, such as its high reliability and validity. Highlight the broader impact of having a validated Hindi version of the NDI, such as its potential to inform public health policies and improve clinical practices in rural India. Additionally, suggest specific applications of the NDI-Hi in both clinical and research settings, emphasizing its role in enhancing the understanding and management of neck pain among Hindi-speaking populations. Authors’ response We have amended changes accordingly. Regards, Thank you"
}
]
}
] | 1
|
https://f1000research.com/articles/12-1599
|
https://f1000research.com/articles/13-909/v1
|
08 Aug 24
|
{
"type": "Opinion Article",
"title": "Articulating the ultimate objectives of research capacity strengthening programmes: Why this is important and how we might achieve it.",
"authors": [
"Justin Pulford",
"Meshack Nzesei Mutua",
"Imelda Bates",
"Nadia Tagoe",
"Meshack Nzesei Mutua",
"Imelda Bates",
"Nadia Tagoe"
],
"abstract": "‘Research capacity strengthening’ (RCS) is an umbrella term that can be used to describe a wide variety of activities conducted in support of diverse objectives premised upon distinct, potentially opposing, views. Despite this, the ultimate objective of RCS activities is rarely made explicit which can be problematic when diverse objectives are possible. By ‘ultimate’ objective we are referring to the overarching (often long-term) goal an RCS initiative is intended to contribute towards (e.g. better population health) as opposed to the more immediate ‘proximate’ (often short-term) objectives of any such activity (e.g. improved capacity to undertake infectious disease research). We argue a need for those funding, designing and implementing RCS initiatives to make clear statements as to the ultimate objective that they foresee their respective initiative contributing towards as well as the proposed pathway and associated assumptions that underlie their approach. Examples of distinct ultimate objectives for RCS initiatives are presented alongside fictitious examples of how they may be transparently reported from both a funder and implementor perspective. Such transparency should be routine within the scope of funding calls for RCS activities (even when such activities are only a minor component of the call), subsequent applications to those calls and any description of an applied RCS activity/ies and/or the associated outcomes thereof. The process of determining one’s ultimate objective will further cause funders and actors to think through their respective initiatives more thoroughly and make informed choices and better designed RCS projects. Doing so would reduce any ambiguity associated with the use of the term ‘research capacity strengthening’ and would provide a stronger foundation for robust programme evaluation.",
"keywords": [
"Research capacity strengthening",
"evaluation",
"global South"
],
"content": "Introduction\n\nThere is a long history of governments, development partners and philanthropic organisations financing research capacity strengthening (RCS) initiatives in the global South. Common examples, among many others, include scholarship schemes, infrastructure grants and collaborative research awards. The cumulative investment in RCS support within the global South has not been calculated but would certainly exceed several billion GBP and counting. As an example, the UK government and Wellcome spent £873 million between 2016-2021 on dedicated RCS initiatives in the global South with a further £1.2 billion expended on research activities with a capacity strengthening component.1 Benefits of RCS investment have been widely reported in the literature2–4 and gains in Southern research capacity are apparent in measures such as scientific publication output.5 Nevertheless, much of this investment is based on very little evidence of the effectiveness or impact on long term outcomes. Southern research capacity remains well behind Northern standards on most metrics6,7 and there is still much to be learnt about the value for money of these investments and about the pathways by which impact in the global South is achieved.4\n\nLimited understanding of RCS impact reflects, in part, a lack of sound evaluation.8,9 RCS is a long-term, multi-faceted and complex undertaking and the tools to support robust, standardised evaluation are only beginning to emerge.10–12 A further factor confounding evaluation efforts is a pervasive ambiguity in the use of the term ‘research capacity strengthening’ itself. RCS is not a construct in its own right; rather, RCS is an umbrella term that can be used to describe a wide variety of activities conducted in support of diverse objectives premised upon distinct, potentially opposing, views (see further below for examples). Despite this, the RCS term is often used with a false assumption of neutrality13 and without a clear definition being provided.8 Those definitions that are presented are highly diverse and typically process oriented, yet it is not at all apparent whether different definitions of RCS represent distinct conceptualisations of RCS as an undertaking or whether (as is more likely) they are being used with a broadly consistent (yet often ambiguously stated) meaning (see Box 1). Even the term ‘research capacity strengthening’ is often used interchangeably with the terms ‘research capacity building’ and ‘research capacity development’8 despite attempts to differentiate their meaning.9,14 Without absolute transparency about the agreed explicit, ultimate objective of an RCS initiative, and the assumptions upon which it is based, then our ability to advance understanding of what works well and why in RCS practice through applied research, evaluation and shared learning is compromised. By ‘ultimate’ objective we are referring to the overarching (often long-term) goal an individual RCS initiative is intended to contribute towards (e.g. better population health) as opposed to the more immediate ‘proximate’ (often short-term) objectives of any such activity (e.g. improved capacity to undertake infectious disease research). Proximate objectives remain important; they are just not the focus of this paper.\n\nA scoping review of health-related RCS papers published in academic journals between 2000-2016 identified a total of 172 papers of which only 19% (33/172) presented some form of RCS definition8. In the 33 papers that did so, a total of 25 distinct definitions were provided. Seventeen of these 25 definitions pertained to either ‘health research capacity strengthening’ or ‘research capacity strengthening’ (or variants thereof such as ‘research capacity building’) whilst the remaining eight pertained to broader definitions of ‘capacity strengthening’ (or variants thereof) that were not specific to research. Many of these definitions emphasised RCS as a ‘process’ without specifying an objective beyond strengthened capacity, e.g.\n\n“Process of individual and institutional development which leads to higher levels of skills and greater ability to perform useful research.”15\n\n“A long-term process that requires a systematic and inter-sectoral approach to developing appropriate regulatory frameworks, building and maintaining physical infrastructure, and investing in human resources, equipment and training in an environment conducive to research commitment and institutional support.” 16\n\nIn definitions where an objective was indicated, this was typically couched in terms of the capacity to identify and resolve ‘problems’, e.g.\n\n“The ongoing process of empowering individuals, institutions, organisations, and nations to: define and prioritise problems systematically; develop and scientifically evaluate appropriate solutions; and share and apply the knowledge generated.”17\n\n“Strengthening the abilities of individuals, institutions, and countries to perform research functions, defining national problems and priorities, solving national problems, utilizing the results of research in policy making and programme delivery.”18\n\nThe latter examples explicitly draw a link between research capacity and national development (as described below), although this does not then mean that other definitions are used in support of a different objective; it is simply not possible to tell unless the ultimate objective is clearly articulated.\n\nThe aim of this paper is to justify and promote the need for transparency in RCS practice in making the ultimate RCS objective(s) explicit and to provide some recommendations as to how this might be achieved. Not only will this support more effective learning and evaluation, greater clarity of purpose for any RCS activity will also help inform the design and implementation processes to ensure that they are compatible with, and contribute towards achieving, the stated objectives. To substantiate our argument, we outline three different ultimate objectives for RCS activities. We also highlight the considerable scope for distinct and potentially divergent pathways through which RCS activities might support these objectives, even when the ultimate objective is agreed, well-defined and shared. In so doing, we are not endorsing any one approach over another, we are merely demonstrating that the common term ‘research capacity strengthening’ can be used to describe a wide range of potentially divergent activities. The examples we provide should not be considered exhaustive. Further examples, with differing implications, are almost certainly possible and we would encourage others to articulate these in the public domain and to challenge and refine those presented here. We will begin with a description of what appears to be the most common ultimate objective for RCS investment in the global South: (inter) national development.\n\nMuch contemporary RCS practice in the global South, whether explicitly stated or not, is conducted within an international development context. By ‘international development’ we are referring to any contributory effort towards improving the health and/or development status of the intervention country. This positioning is evidenced in the two statements quoted below. The first from the United Nation’s Development Programme (UNDP) referring to the importance of capacity development more broadly (inclusive of, but not limited to research capacity) and the second from the Council on Health Research Development (COHRED) referring to a specific type of RCS (health):\n\n“A country’s successful development hinges on having sufficient capacity. While financial resources, including official development assistance, are vital, they are not enough to promote sustainable human development. Without supportive strategies, policies, laws and procedures, well-functioning organizations, and educated and skilled people, countries lack the foundation to plan, implement and review their national and local development strategies”.19\n\n“We find that essential national health research is a critical tool for equitable health and development and therefore recommend that each developing country, taking account of its own circumstances, make careful plans for and carry out sustained, long-term programs for building research capacity and conducting essential national health research.”20\n\nThe ultimate objective of any RCS initiative conducted within an international development context, then, would be a measurable improvement in a nation’s health and/or development status. However, there are diverse views on what factors, processes or systems may best drive national development which will in turn influence decisions as to what specific development objectives should be prioritised and what corresponding research capacities need to be strengthened. Thus, referencing ‘(inter) national development’ as a RCS objective remains obscure if the type of development sought, the specific development objectives and the proposed pathway towards achieving them are not articulated. For example, proponents of market economics might recognise a transition towards a knowledge-based economy as a key driver of socio-economic development and on this basis prioritise RCS in science, technology, engineering and mathematics (STEM) as essential precursors to any such transition. Others may prioritise national health research capacity on the basis that population health is fundamental to national development per se, irrespective of the underlying economic model. Alternatively, RCS initiatives may be based on achieving progress against a specific development indicator, such as one or more of the sustainable development goals (SDGs); which scientific disciplines or research fields are then prioritised for capacity strengthening would vary accordingly.\n\nRCS interventions undertaken within an international development context may also vary in terms of design, even when prioritising the same development objective or scientific discipline. RCS initiatives have historically focused on strengthening capacity of individuals, such as researchers and research team members, as opposed to the institutions or broader research systems they work within,21 yet funders are now increasingly emphasising the importance of institutional and systems level interventions.22 RCS investments have also often emphasised notions of ‘research excellence’ on the premise that it is innovative, high-quality research that drives development.23 However, this can result in disproportionately large investment in a smaller number of the comparatively better capacitated universities and research institutions in the global South further exacerbating local, national or regional disparities in research capacity.24–26 Thus, the concept of equity has become a key consideration in the field with a view towards more power and resources being directed towards the less-well capacitated individuals, institutions, and nations across the global South.27 There is limited evidence-based guidance to inform which of the many possible variations in RCS approach may be most effective in terms of supporting an international development objective whatever the specific objective might be. Rather, legitimate arguments can be made in support of multiple approaches and different RCS initiatives make different choices, even when operating within the same overarching programme.28\n\nWithout clear statements as to the specific development objectives sought and the proposed pathway towards achieving these objectives, it becomes difficult to design and implement optimally conducive RCS activities and evaluate their success. To illustrate, in some of the examples presented above different scientific disciples or research fields are being prioritised for capacity strengthening (STEM vs health research vs SDG appropriate research) yet it would not be possible to make or to understand these prioritisation decisions without at least some understanding of the underlying development objective. Similarly, the approach and ethos to designing and implementing the RCS activities once the specific objective was agreed would also likely vary across these examples. Notions of attaining research excellence within the defined standards of a Northern research tradition may be highly appropriate to RCS activities that prioritise STEM subjects in support of transitioning towards a knowledge economy, yet the same approach may be less compatible with RCS activities undertaken in support of empowering local community health initiatives. No one approach is necessarily more or less appropriate than any other, nor indeed would any one approach be exclusive to any one development objective; however, clarity as to the RCS purpose in each case would likely signal the more suitable implementation approach further enhancing capacity outcomes and providing a clearer basis for subsequent evaluation.\n\nTo further complicate the situation, we now argue that RCS in the global South can also be conducted outside of an international development context altogether. We present two such possibilities: 1) RCS in support of knowledge as a common good and 2) RCS in support of decolonisation.\n\n\nRCS activities outside of an international development context\n\nKnowledge has long been regarded as a form of common or public good29 as have public Universities.30 The extent to which (all) scientific knowledge may be considered a common good or the extent to which public universities are genuinely in the public good are open to debate.30,31 However, within the parameters of these ongoing debates, it remains plausible to frame RCS investment (or at least some forms of RCS investment) as a contribution to the common good. This may overlap with an international development approach to some degree, as scientific knowledge that supports international development may also be considered a common good29; yet it also encompasses scientific disciplines and research fields such as Philosophy, Theology or History that are less likely to attract funding within an international development context. The ultimate objective of any such RCS investment would not be the outcome of knowledge application (e.g. such as a development goal), but a measurable increase in the quantity, quality, diversity and/or access to (scientific) knowledge itself.\n\nRCS investments could also potentially be framed within a decolonisation context. It is widely recognised that a consequence of the European colonial era was the disruption, degradation or destruction of traditional customs and bodies of knowledge among colonised people.32 Colonisation also instituted the imposition of the coloniser’s ideals, practices and standards which ended up suppressing indigenous knowledge practices.33 It would therefore be reasonable to consider strengthening capacity for research that supports the restitution of traditional knowledge bodies and/or strengthening local systems of research as conceptualised by the formerly colonised peoples or their descendants. The ultimate objective of any RCS activity in such instances would be greater recognition of indigenous knowledge systems and promotion of self-determination at local/national/regional levels regarding capacity goals, needs and the pathways towards achieving specified goals. As with the international development example, the RCS activities conducted in support of either a common good or decolonisation objective, along with the proposed pathways to impact and associated assumptions, would also be open to considerable variation.\n\nThese examples demonstrate that activities described as ‘research capacity strengthening’ can be implemented in support of diverse ultimate objectives and premised upon a multitude of legitimate, yet potentially very different, pathways to achieving their respective objective. Distinct scientific disciplines or research fields may be more or less likely to receive capacity strengthening support depending upon what the ultimate objective is and, in some cases, these prioritisation decisions could be diametrically opposed. Hence the call for greater transparency re the ultimate objectives when describing or reporting on future, current or past RCS activities. In practice, RCS programmes may have multiple or over-lapping objectives. For example, Mormina and Istratii recently argued a case for a decolonisation approach to RCS in support of international development objectives13 and, as noted above, science conducted as a common good may also support development objectives in some instances. This is in no way problematic if the primary or overlapping ultimate objectives are clearly articulated. When such transparency is lacking, as argued above, it becomes difficult to evaluate the outcomes of a RCS intervention or even to design and implement an intervention in a manner optimally conducive to achieving the objective. This is analogous to any other ‘experiment’ i.e. if the ultimate objective is not clearly stated from the outset, alongside any associated assumptions as to how best to achieve that objective, then how can an optimal intervention be designed in the first instance?\n\n\nAchieving transparency in practice\n\nTo aid the appropriate interpretation of RCS activities as well as subsequent learning and evaluation, we propose that those funding, designing and implementing RCS initiatives make clear statements as to the ultimate objective that they foresee their respective initiative contributing towards. They should also describe the proposed pathway and associated assumptions that underlie their approach. Key principles that are expected to be, or were, prioritised in RCS design and implementation such as ‘excellence’, ‘equity’ or ‘collaboration’ may also be emphasised. These statements do not need to be overly complex or lengthy. To illustrate, some fictitious examples of transparent statements about the ultimate RCS objectives from both a funder and implementor perspective are presented below, along with a note on how they support transparent RCS reporting and would inform subsequent evaluation (Box 2).\n\nExample 1: RCS in support of international development\n\nFunder statement: This programme is designed to strengthen research capacity in STEM-related disciplines in ODA-eligible countries. The programme is premised on the view that greater national research capacity in STEM-related disciplines will provide a stronger foundation for the development and uptake of innovative, locally appropriate technical solutions to priority national and regional challenges and contribute towards economic growth through innovation-led commerce and enterprise.\n\nImplementor statement: Our project is designed to strengthen research capacity in computational modelling in [name of focal nation/s]. We will achieve this by supporting the development of a specialist ‘centre of excellence in computational modelling’ housed within the University of X and supporting them to cascade these skills to other institutions. This approach is premised on the view that the fastest and most efficient way to develop research capacity in computational modelling in [nation] is through intensive investment of time and resources within a specialist centre that can then support the development of similar expertise in other institutions throughout the country and region (i.e. a ‘hub and spoke’ model).\n\nComment: The ultimate objectives (addressing priority national/regional challenges & contributing towards socio-economic development) of the RCS funding are made clear in the funder statement as is the pathway towards achieving these objectives (STEM-derived innovative, locally appropriate technical solutions with potential for commercialisation). The implementor statement makes clear the approach (investment in a computational modelling centre of excellence) with which their project will contribute towards the ultimate objective as well as the assumptions underlying this pathway (fastest way to build capacity in the short-term and efficient in the long-term when considered the’ hub’ for future ‘spokes’). Evaluation of this RCS project would therefore look for examples of technical solutions that the centre for computational modelling has developed (or is currently developing) that have addressed (or could potentially contribute towards addressing) a national/regional challenge and/or that have been (or potentially could be) commercialised.\n\nExample 2. RCS in support of knowledge as a common good\n\nFunder statement: This programme is designed to strengthen research capacity in the Arts and Humanities. The programme is premised on the view that creating, and ensuring access to, new knowledge from across traditional academic disciplines is in the common good. The Arts and Humanities have been prioritised in this instance as, relative to many other academic disciplines, research funding in these fields is scarce.\n\nImplementor statement: Our project is designed to support five early career researchers, one from each of five universities belonging to our consortium, to undertake three-year post-doctoral study within an Arts and Humanities subject of their choosing. Along with the financial resources necessary to undertake their study, each scholar will be provided expert mentorship and specialist leadership training to assist their career development and we will support the production of multiple, publicly accessible outputs (e.g. books, artwork, film) arising from their work. This approach is premised on the view that each University within our consortium should have the right to self-determine which Arts and Humanities discipline is prioritised for funding in their context. Our approach further recognises that early career researchers in the Arts and Humanities need specialist funding and guidance to develop a productive and sustainable career in what is a competitive academic environment and that the value of their work to society will be best served by ensuring that it is made readily accessible in easy to understand and engaging ways.\n\nComment: The ultimate objective (contributing to the common good) of the RCS funding is made clear in the funder statement as is the premise upon which the Arts and Humanities were prioritised (neglected relative to other academic disciplines). The implementor statement makes clear the pathway (mentored and resourced early career researcher scholarships and support to produce accessible outputs) with which their project will contribute towards the ultimate objective as well as the assumptions underlying this pathway (scholars in Arts and Humanities need specialist funding and support to develop and sustain careers in a competitive environment). Evaluation of this RCS project would therefore look for examples of outputs that represent new knowledge and evidence that this knowledge has been made accessible to, and has been accessed by, the public.\n\nExample 3. RCS in support of decolonisation\n\nFunder statement: This RCS programme is designed to strengthen indigenous knowledge and/or knowledge systems in [nation]. This investment is provided by [donor] in recognition that indigenous knowledge/knowledge systems are a precious national and global resource. All decisions related to how this funding will be used to support RCS within [nation], including how the notion of research is conceptualised, is for [nation] to self-determine.\n\nImplementor statement: Our project is designed to ensure the oral histories of [a people] are recorded for posterity and made accessible for the national good. It is our belief that a full understanding of our nation’s people, our current place in the world and our future pathways is not possible without reference to our own unique histories which are at risk of being lost or neglected if not recorded and communicated in ways that everyone in our society can engage with.\n\nComment: The ultimate objective (strengthen indigenous knowledge and/or knowledge systems) of the RCS funding is made clear in the funder statement as is the premise upon how the funding will be used to support this objective (for the recipient nation to self-determine). The implementor statement makes clear how the funding will be used in support of this objective (record oral histories) as well as the assumptions underlying this decision (it is in the national good to do so and a risk of oral histories being lost or neglected if the work is not undertaken). Evaluation of this RCS project would therefore look to establish that the work was self-determined independent of funder influence and that there was a measurable increase in, and/or access to or influence of, indigenous knowledge.\n\nThese examples illustrate what should be considered a minimum acceptable level of transparency. Understanding of any RCS activity would be further enhanced by fuller descriptions of proposed impact pathways and there are widely used methods and tools for doing so, including the use of programme Theories of Change,34 logic models35 and even specialist frameworks intended to support better, more transparent RCS practice and evaluation.12 Even basic descriptions such as those presented above would represent a considerable improvement in transparent reporting of RCS activities if they were applied in practice. Such transparency should be routine within the scope of funding calls for RCS activities (even when such activities are only a minor component of the call), subsequent applications to those calls and any description of an applied RCS activity/ies and/or the associated outcomes thereof. The process of determining one’s ultimate objective will further cause funders and actors to think through their respective initiatives more thoroughly and make informed choices and better designed RCS projects. Doing so would reduce any ambiguity associated with the use of the term ‘research capacity strengthening’ and would provide a stronger foundation for robust programme evaluation. From such a foundation, and with appropriate investment to support routine evaluation, the research community will be in a strong position to greatly accelerate our ability to understand what works well, and not so well, in our collective RCS endeavours.\n\nNo ethics and consent required.",
"appendix": "Data and software availability\n\nNo data are associated with this article.\n\n\nReferences\n\nUKCDR: UK funding landscape for research capacity strengthening in low- and middle-income countries: briefing paper, October 2021. London: UK Collaborative on Development Research; 2021.\n\nAiyenigba A, Abomo P, Wiltgen Georgi N, et al.: Enabling research capacity strengthening within a consortium context: a qualitative study. BMJ Glob. Health. 2022; 7(6): e008763. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVicente-Crespo M, Agunbiade O, Eyers J, et al.: Institutionalizing research capacity strengthening in LMICs: A systematic review and meta-synthesis. AAS Open Res. 2020; 3: 43. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBuser JM, Capellari E, Wondafrash M, et al.: Unravelling the complexity of research capacity strengthening for health professionals in low- and middle-income countries: A concept analysis. J. Adv. Nurs. 2024. [published Online First: 20240516]. PubMed Abstract | Publisher Full Text\n\nConfraria H, Godinho M: The impact of African science: A bibliometric analysis. Scientometrics. 2015; 102: 1241–1268. Publisher Full Text\n\nUNESCO: UNESCO Science Report: the Race Against Time for Smarter Development. Schneegans S STaJL, ed. Paris: UNESCO Publishing; 2021.\n\nNabyonga-Orem J, Asamani J, Olu O: Why are African researchers left behind in global scientific publications? A viewpoint. Int. J. Health Policy Manag. 2024; 13: 8149.\n\nDean L, Gregorius S, Bates I, et al.: Advancing the science of health research capacity strengthening in low-income and middle-income countries: a scoping review of the published literature, 2000-2016. BMJ Open. 2017; 7(12): e018718. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFranzen SR, Chandler C, Lang T: Health research capacity development in low and middle income countries: reality or rhetoric? A systematic meta-narrative review of the qualitative literature. BMJ Open. 2017; 7(1): e012332. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWenham C, Wouters O, Jones C, et al.: Measuring health science research and development in Africa: mapping the available data. Health Res. Policy Syst. 2021; 19(1): 142. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhisa AM, Gitau E, Pulford J, et al.: A framework and indicators to improve research capacity strengthening evaluation practice. Liverpool: Liverpool School of Tropical Medicine and the African Population Health Research Centre.2019.\n\nMirzoev T, Topp SM, Afifi RA, et al.: Conceptual framework for systemic capacity strengthening for health policy and systems research. BMJ Glob. Health. 2022; 7(8): e009764. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMormina M, Istratii R: ‘Capacity for what? Capacity for whom?’ A decolonial deconstruction of research caapcity development practices in the Global South and proposal for a value-centred approach. Wellcome Open Res. 2021; 6(129). Publisher Full Text\n\nZamfir L: Understanding capacity-building/capacity-development: A core concept of development policy. Brussels: European Parliamentary Research Service; 2017.\n\nGolenko X, Pager S, Holden L: A thematic analysis of the role of the organisation in building allied health research capacity: a senior managers’ perspective. BMC Health Serv. Res. 2012; 12: 276. [published Online First: 20120827]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOsei-Atweneboana MY, Lustigman S, Prichard RK, et al.: A research agenda for helminth diseases of humans: health research and capacity building in disease-endemic countries for helminthiases control. PLoS Negl. Trop. Dis. 2012; 6(4): e1602. [published Online First: 20120424]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLansang MA, Dennis R: Building capacity in health research in the developing world. Bull. World Health Organ. 2004; 82(10): 764–770. PubMed Abstract\n\nKilic B, Phillimore P, Islek D, et al.: Research capacity and training needs for non-communicable diseases in the public health arena in Turkey. BMC Health Serv. Res. 2014; 14: 373. [published Online First: 20140905]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUNDP: Supporting Capacity Development: The UNDP Approach. New York: United Nations Development Programme Bureau for Development Policy; 2009.\n\nCOHRED: Health research: essential link to equity in development. New York: Commission on Health Research for Development (COHRED); 1990.\n\nMormina M: Science, Technology and Innovation as Social Goods for Development: Rethinking Research Capacity Building from Sen’s Capabilities Approach. Sci. Eng. Ethics. 2019; 25(3): 671–92. [published Online First: 20180301]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nESSENCE on Health Research and CCR: Effective Research Capacity Strengthening: A Quick Guide for Funders.2023.\n\nKraemer-Mbula E, Tijssen R, Wallace M, et al.: Transforming Research Excellence: New Ideas from the Global South. Cape Town, South Africa: African Minds; 2020.\n\nYarmoshuk A, Abomo P, Fitzgerald N, et al.: A mapping of health professional and post-graduate health programs in the WHO African Region. AAS Open Res. 2021; 4(55). Publisher Full Text\n\nMorel T, Maher D, Nyirenda T, et al.: Strengthening health research capacity in sub-Saharan Africa: mapping the 2012-2017 landscape of externally funded international postgraduate training at institutions in the region. Glob. Health. 2018; 14(1): 77. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKilmarx PH, Maitin T, Adam T, et al.: A Mechanism for Reviewing Investments in Health Research Capacity Strengthening in Low- and Middle-Income Countries. Ann. Glob. Health. 2020; 86(1): 92. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaher D, Aseffa A, Kay S, et al.: External funding to strengthen capacity for research in low-income and middle-income countries: exigence, excellence and equity. BMJ Glob. Health. 2020; 5(3): e002212. [published Online First: 20200317]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTagoe N, Pulford J, Kinyanjui S, et al.: A framework for managing health research capacity strengthening consortia: addressing tensions and enhancing capacity outcomes. BMJ Glob. Health. 2022; 7(10): e009472. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStiglitz JE: Knowledge as a Global Public Good.Kaul I, Grunberg I, Stern M, editors. Global Public Goods. New York: Oxfor University Press; 1999.\n\nMarginson S: Higher education and the public good. High. Educ. Q. 2011; 65(4): 411–433. Publisher Full Text\n\nRadder H: Which Scientific Knowledge is a Common Good? Soc. Epistemol. 2017; 31(5): 431–450. Publisher Full Text\n\nZiegler J, Lehner E: Knowledge systems and the colonial legacies in African science education. Cult. Stud. Sci. Educ. 2018; 13: 1101–1108. Publisher Full Text\n\nKoum Besson ES: How to identify epistemic injustice in global health research funding practices: a decolonial guide. BMJ Glob. Health. 2022; 7(4): e008950. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMayne J: Theory of change analysis: Building robust theories of change. Can. J. Program Eval. 2017; 32(2): 155–173. Publisher Full Text\n\nMcLaughlin J, Jordan G: Using Logic Models.Newcomer K, Hatry H, Wholey J, editors. Handbook of Practical Program Evaluation. Wiley; 2015; pp. 62–87."
}
|
[
{
"id": "313114",
"date": "03 Sep 2024",
"name": "Elizabeth S Rose",
"expertise": [
"Reviewer Expertise education & training (including public health and medical student education",
"faculty development",
"curriculum design)",
"decolonizing global health",
"research capacity strengthening"
],
"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 have begun an excellent discussion about the lack of a definition for research capacity strengthening (RCS). They provided evidence of the array of RCS definitions in the academic literature as well as the number of articles about RCS that do not define the term. The authors also discuss the diverse views of 'international development,' which subtly (and not so subtly) is a root of most RCS initiatives. They present a new view on RCS in decolonization. Although RCS could be seen as another form of colonization (e.g., institutions from the 'global north' deciding who needs to be 'capacitated'), the authors propose that goals of RCS should be aimed towards \"greater recognition of indigenous knowledge and promotion of self-determination at local/national/regional levels,\" which would promote research and knowledge independence. The authors' proposal that funders, implementers, and others define RCS by including their ultimate goal in the project will help those individuals and organizations to have more clarity about their work and provide transparency in this space. Such transparency and additional thought about RCS initiatives prior to work starting could contribute to projects that better support equity and independence.\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": "313119",
"date": "05 Sep 2024",
"name": "Maru Mormina",
"expertise": [
"Reviewer Expertise research capacity development in international development",
"systems thinking",
"wicked problems",
"epistemology",
"ethics",
"science and technology studies."
],
"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 to the authors for such a thoughtful commentary and their valuable attempt to bring clarity and transparency to a practice that remains poorly defined and poorly understood. Research capacity building (RCB), strengthening (RCS) or development ( RCD) are much misused and abused umbrella terms, used to encompass anything and everything but more often associated with training and development of the research workforce (researchers but also government officials, health workers, and other actors engaged in generating and using research and evidence). This is not only confusing, it is highly reductive: developing research capacity entails far more than a transfer of technical skills, but developing often intangible competencies, including the ability and opportunities to absorb and produce the tacit knowledge that underpins much of the research and innovation process. The article acknowledges this ambiguity and calls for transparency not only in what those doing or funding RCS mean by it but also what they are trying to achieve, i.e. the ultimate goal. After all, without a clear understanding of where we want to go, how do we select the route, and crucially, how do we know whether we have arrived? That RCS initiatives should be clear about their goals is intuitive and the authors provide good examples (quite possibly inspired by their own experience in this field) to illustrate how an explicit articulation of long term goals helps inform a more effective design of capacity building activities and contributes to a more robust monitoring and evaluation of programmes. Whilst the proposition is very well-argued and difficult to disagree with, I feel there are two considerations that the authors have left unaddressed, possibly due to space constraints. Nonetheless, I think they are important to acknowledge, reflect upon, and, if possible, discuss in future updates of the paper. The first and most important consideration is complexity. Whether capacity building contributes to the ultimate goal of international development, decolonisation or the common good, these goals are 'wicked problems' for which cause-effect pathways (and their respective linear theories of change) are difficult to recognize. Wicked problems are an entangled web of issues that are part of an interconnected and interdependent system, so that fixing one part of the system will cause (often unpredictable) effects in other parts of the system. Given the wicked nature of the systems that RCS activities aim to impact, it is unclear whether we will ever be able to determine with any certainty a causal relationship between a particular capacity building activity and its ultimate goal. Evaluators, at most can evaluate the activities' contribution to proximate goals, in which case the value of articulating ultimate goals lies not so much in the evaluation of RCS but perhaps in making clear the need to approach RCS as a systemic intervention. This brings me to my second point. As the authors will undoubtely know, there is a great deal of wasteful fragmentation, duplication and reinventing of the wheel in international development, and capacity building is no exception. Funders are largely responsible for this, although recent years have seen more concerted efforts at integration and collaboration, with joint programmes increasingly becoming the norm. I would have liked to see this addressed in this commentary and I invite the authors to reflect on how their call to transparency with regards to the ultimate goals could help funders and RCS actors take more systemic approaches consistent with the wicked nature of the problems they are trying to solve. My personal view, perhaps biased, is that the true benefit of a more transparent articulation of the ultimate goals of RCS lies in that it exposes the wicked nature of development problems and forces actors to recognise the need for, and seek pathways to, systemic integration through collaboration.\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
|
https://f1000research.com/articles/13-909
|
https://f1000research.com/articles/13-907/v1
|
08 Aug 24
|
{
"type": "Research Article",
"title": "Evaluation of NETosis (Neutrophil Extracellular Traps) biomarkers in smokers and nonsmokers periodontitis patients",
"authors": [
"Rasha Abdul Jabbar Najim",
"Batool Hassan Al Ghurabi",
"Batool Hassan Al Ghurabi"
],
"abstract": "Background To evaluate the NETosis biomarkers citrullinated histone H3 (citH3), neutrophil elastase (ELA), calprotectin (CALPRO), and myeloperoxidase (MPO) as indicators of inflammation in the severe stages of periodontitis III and IV in both (smokers and nonsmokers) patients, and to determine the correlation between NETosis biomarkers and clinical periodontal parameters.\n\nMethods This study recruited male subjects with an age range of (20-60) years; 60 were stage III and stage IV periodontitis patients, 30 were cigarette smoker, and 30 were nonsmokers. After applying the inclusion and exclusion criteria to evaluate their eligibility for recruitment, 25 control subjects with a healthy periodontal status and good oral hygiene maintenance were included. Unstimulated saliva was obtained and evaluated using an enzyme-linked immunosorbent assay, and the following periodontal parameters were documented: [plaque index, bleeding on probing, periodontal pocket depth, and clinical attachment loss].\n\nResults The mean levels of all salivary NETosis biomarkers citH3, ELA, CALPRO, and MPO were elevated in the periodontitis groups (smokers and nonsmokers) than in controls. Moreover, the mean NETosis biomarker‘s mean levels were significantly higher in smoker than in nonsmokers. In addition, the correlations were significant between CALPRO and CitH3 in smokers and between ELA and CitH3 in nonsmokers.\n\nConclusions The results of this study showed that the chosen salivary biomarkers of NETosis revealed elevated clinical accuracy in differentiating the studied periodontitis groups (smokers and nonsmokers) from controls. In addition, cigarette smoking increases the risk of periodontitis, and neutrophils in smokers with periodontitis exhibited more susceptibility to form neutrophil extracellular traps when compared with nonsmokers.",
"keywords": [
"Biomarkers",
"Calprotectin",
"Citrullinated histone H3",
"Myeloperoxidase",
"NETosis",
"Neutrophil elastase",
"Periodontitis"
],
"content": "Introduction\n\nPeriodontitis is a multifactorial chronic, irreversible inflammation; however, the primary cause of periodontitis has been found to be the bacterial biofilm that develops on tooth surfaces, the host’s reaction, in addition to local elements such as genetics, plaque, calculus, external factors, and the health of the patients in general, all of which influence disease progression.1 Smoking is one of the main ways in which individuals are exposed to harmful chemicals (cigarette smoke contains at least 4,500 different chemicals), and can cause epigenetic changes that increase inflammation. In addition, smoking generally increases oxidative stress, with excess free oxygen radicals causing cell damage. As a result, smoking exacerbates periodontal disease and negatively affects nearly all forms of periodontal therapy.2,3 Several studies have indicated that smokers are more likely to have periodontal disease than nonsmokers, including greater gingival recession, bone attachment, and tooth loss.4–7 Reactive oxygen species (ROS) released by periodontal infections and their byproducts activate several phagocytes, including neutrophils, monocytes, gingival fibroblasts, and cells found in the periodontal tissue. In patients with periodontitis, there is an increase in the recruitment of polymorph nuclear neutrophils (PMNs), which results in the breakdown of bone and oral tissues,1,8–10 this is because the periodontium is a special habitat where oral bacteria are constantly in contact with the host immune system. Neutrophils serve as the initial line of defense of the human innate immune system and have the ability to eliminate infections extracellularly, connect innate and adaptive immune responses, and support tissue healing and inflammatory resolution.9,11,12 However, severe periodontitis is caused by a lack of neutrophils, and an excess of neutrophils appears to be harmful because it maintains the body in an inflammatory state, which destroys tissue. Maintaining a balance between neutrophils and other macrophages is crucial for maintaining periodontal homeostasis, as an imbalance can result in periodontitis.8,13 According to these recent studies,3,14 smoking cigarettes has several potential detrimental effects on periodontal health, including a decrease in wound healing time, vascular constriction, impaired defenses against plaque bacteria, and interference with oxidative stress processes. Because they disturb redox equilibrium, reactive oxygen species (ROS) are toxic to humans, and exposure to cigarette smoke increases their levels. However, sex hormones may also affect the gingival microcirculation, which can affect the global spread of the disease. Men are substantially more likely than women to show vasodilation in case of inflammation or when a wound is healing and when the disease is actively progressing.3,15–19 Neutrophil equilibrium is important in periodontal homeostasis because periodontitis can develop when there are too many or too few neutrophils in the tissue.8 One means by which Neutrophils aid in homeostasis and defense by producing neutrophil extracellular taps (NETs), which allow them to capture bacteria in the extracellular space by releasing decondensed chromatin adorned with histones and granule content. NETosis is defined as the occurrence of neutrophil death and NET production. The primary defense of periodontal tissues is provided by NETs, and a deficiency in NETs can result in severe early-onset periodontitis.9,18–19 Smoking cigarettes accelerates the production of NETs and PMN-derived proteases, which are responsible for breaking down connective tissue.2,14 NETs are composed of DNA and histones, along with associated neutrophil granule proteins such as citH3, Neutrophil Elastase, Calprotectin and Myeloperoxidase.12 Histone H3 is the most abundant protein in NETs, and citrullination of histones is a specific marker of NETosis.20,21 ELA is a serine protease maintained in abundance in azurophilic granules of neutrophils, together with other proteins involved in anti-microbial defense, and high levels of ELA in saliva can be associated with the loss of active periodontal attachment.22 CALPRO belongs to the S100 family, which accounts for 5–40% of the cytosolic protein content of neutrophils. It acts as a new warning system by demonstrating pro-inflammatory activities primarily induced by activated granulocytes in a calcium-dependent manner. It contributes by binding to specific cell surface receptors, which sets off further signal transductions that contribute to the recruitment of white blood cells and production of inflammatory cytokines in the affected regions.23 One of the many mediators released in tissues as inflammation advances is MPO, whose expression is highly correlated with gingival tissue in periodontitis.24 Based on the available evidence, this study evaluated the NETosis biomarkers as indicators of inflammation in stage III and stage IV (smokers and nonsmokers) periodontitis groups and compared the findings with those of the controls. Furthermore, we determined the relationship between the NETosis biomarkers and clinical periodontal parameters.\n\n\nMethods\n\nThis was a case-control study based on observational data. The study was carried out in the Periodontics Department/College Dentistry, University of Baghdad, Al-Baladiat specialized center for dentistry, Al Sader specialized center for dentistry, and Nawar Mousa specialized center for dentistry in Baghdad/Iraq, from October 18, 2023, to January 2024. Ethical considerations were essential during the conduct of this study, introduced by the World Medical Association’s Helsinki Declaration (WMA), after submission to the ethical committee at the Dentistry College/University of Baghdad to obtain ethical approval (Reference Number: 844, project number: 844823, date: 15-10-2023).\n\nThe 85 male subjects recruited in the study and selected according to their oral and periodontal health status, the type of this study was case control study not clinical trial study, Depending on the classification criteria by Tonetti,25 the selected patients were classified into:\n\n• Periodontal healthy control group with intact periodontium.\n\n• Stage III periodontitis (loss of bone reaches the root’s midpoint).\n\n• Stage IV periodontitis (loss of bone reaches the apical third of the root). Each periodontitis group was further subcategorized into two groups:\n\n• Smokers (stage III and stage IV).\n\n• Non-smokers (stage III and stage IV).\n\nAll males recruited in the study had at least 20 teeth and no systemic disease with no antibiotic consumption for the last 3 months. The control group with healthy periodontium exhibiting good oral hygiene without any periodontal disease history or symptoms with intact periodontium (BOP<10% and PPD≤3),26 On the other hand, cases of periodontitis were chosen based on the following criteria,25 which defined the disease as having visible interdental CAL at two or more teeth that are not adjacent, CAL measuring more than 3 mm along with pocketing measuring at least 3 mm, can be found at two or more teeth, stage III and stage IV, in which the percentage of the loss of bone reaches the midpoint and apical third of roots, as well as unstable with the depth of the pocket of more than 5 mm or when bleeding occurs upon probing at a depth of 4 mm.\n\nThese criteria included subjects with the following: systemic diseases such as autoimmune diseases and diabetes mellitus, history of smoking or alcohol drinking, use of anti-inflammatory drugs and/or antibiotics within the previous three months, use of any periodontal treatment that was used in the past or at present, orthodontic appliances or prosthodontics, consumption of any type of smoke other than cigarettes (electric cigarettes and vapes), oral lesions such as lichen planus, and other diseases unrelated to periodontitis; Females excluded from the study.\n\nThe G power 3.1.9.7 program (developed by Franz-Faull, Kiel University/Germany) was employed to compute the size of the sample. Under these conditions, the sample size is around 85 participants, with a power of 90%, an alpha error of 0.05 on both sides’ results in, a significant effect size of F at 0.4, and three groups.27\n\nEffect size F (Small =0.1, Medium=0.25, Large=0.4).\n\nThe patients were advised to clean and floss their teeth to maintain good oral hygiene. Unstimulated saliva was collected prior to clinical examination. Salivary samples were conducted between 9 am and 12 pm. The participants’ saliva was drooled passively into a plastic cup without any stimulation or spitting, and approximately 3 mL of saliva was collected from each subject. Using a micropipette, saliva was drawn from a disposable cup, transferred to a sterile plain tube, centrifuged at 4000 rpm for 3 min, placed into an uncontaminated Eppendorf tube,28 and then frozen at -20 °C immediately before ELISA analysis for citH3, ELA, CALPRO, and MPO biomarkers.\n\nUsing manual ELISA technology, the levels of citH3 (EPIGEN TEK), ELA, CALPRO, and MPO (Cloud-Clone Corp) biomarkers in saliva were determined for each participant.\n\nFollowing saliva sampling, the clinical parameters (PLI, BOP, PPD, and CAL) and periodontal status was determined using William’s periodontal probe. Six distinct areas of each tooth (Distobuccal, Buccal, Mesiobuccal, Distolingual, Lingual, and Mesiolingual) were inspected to perform clinical parameters BOP/PPD and CAL only, while the scores of PLI were recorded by examining only four surfaces (mesial, distal, labial/buccal, lingual/palatal). The 3rd molar was excluded from the examination of all parameters, except PLI. PLI was recorded using disclosing agents to detect the presence or absence of dental plaque,29 while the percentage of BOP was noted as 1 present 0 absent.30 The distance from the free gingival margin to the base of the pocket is known as PPD, whereas the distance from the cemento-enamel junction (CEJ) to the base of the pocket in the absence of gingival recession is called CAL. If the margin of the gingiva is at the CEJ, then the CAL was considered to be equal the PPD; when there is gingival recession, CAL was determined by adding the recession depth and PPD; and when the margin was higher than CEJ, in order to determine the CAL, the distance from gingival margin to CEJ was subtracted from the PPD.25 Staging was performed by calculating the CAL plus 2 mm of biological width per root length multiplied by 100 for the most affected tooth in the dentition.\n\nThe calibrated periodontal evaluations were completed and performed on five patients not included in the study at the Periodontics Department/Dentistry College/Baghdad. The kappa-coefficient assay was used to examine categorical variables to prevent false-positive results. Clinical periodontal data (PPD and CAL) were recorded every two hours for each of the six sites per tooth (except for the third molars). Measurement reliability was confirmed by the coefficients of intra-class correlation (ICC) of 0.950 for PPD and 0.860 for CAL, while those for PLI and BOP were 0.917 and 0.890, respectively.\n\nData description, analysis, and presentation were performed using the Statistical Package for Social Sciences (SPSS) (version -22/Chicago/Illinois/USA) (https://research-repository.uwa.edu.au/en/publications/spss-statistics-version-22-a-practical-guide).31 For quantitative variables, the descriptive analysis produced the mean and standard deviation (SD), while the percentage and frequency were qualitative variables. The kappa statistical test was employed to evaluate the two readings for dichotomous variables. The linear connection between the two quantitative variables was assessed using the Pearson’s correlation parametric test. Normality of distribution was verified using the Shapiro-Wilk test. Homogeneity was verified using Levene’s test. Two independent sample T test were used to determine how the two groups differed from one another. Two qualitative variables, distributional correlations, were tested using the chi-square test. Receiving operating characteristic curves (ROC) were used to calculate the sensitivity and specificity of each salivary biomarker.\n\nTen participants from the dental teaching hospital at the Dentistry College/Baghdad University participated in a pilot study to investigate the association between NETosis biomarkers (citH3, ELA, CALPRO, and MPO) as indicators of an inflammatory response in smokers and nonsmokers with periodontitis.\n\n\nResults\n\nA total of 150 patients with periodontitis were screened to evaluate their eligibility for recruitment, and 75 people were excluded from the study after applying the inclusion and exclusion criteria to patients undergoing periodontal care clinics. Ultimately, only 60 male patients with periodontitis and 25 controls were included in the study (Figure 1).\n\nWhen comparing the periodontitis groups (smokers and nonsmokers) to the control group, the periodontal parameters of all 85 male study participants increased considerably (Table 1). The mean values of the parameters (PLI/BOP/CAL) were compared among the study groups and showed a significant difference (p<0.05); smokers periodontitis patients had the highest mean levels of PLI and CAL, while the nonsmokers’ group had the highest elevation of the mean percentage of BOP. The smokers group also had a slightly higher mean PPD than the nonsmokers group; however, the results showed non-significant differences in both smokers and nonsmokers stage III and stage IV periodontitis groups.\n\n* , significant p<0.05; n, number; PLI, plaque index; BOP, bleeding on probing; PPD, probing pocket depth; CAL, clinical attachment loss. SP: Smokers periodontitis, NSP: nonsmokers periodontitis.\n\nAccording to multiple pairwise comparisons, as shown in Table 1 between smokers and nonsmokers periodontitis groups, the difference in the average levels of PLI, BOP, and PPD was not statistically significant; however, there was a significant difference in the average CAL of smokers and nonsmokers with periodontitis. The difference in the mean levels of clinical periodontal parameters between the research groups is shown in Figure 2.\n\nTable 2 illustrates that the average levels of salivary biomarkers were higher in the periodontitis groups (smokers and nonsmokers) than in the controls, while the highest level was in the smokers group and the multiple pairwise comparison between the groups was statistically significant.\n\n* Significant, p<0.05;\n\nFigure 3 demonstrates the comparison of the mean level of the NETosis salivary biomarkers (citH3, ELA, CALPRO, and MPO) among the study groups and that the higher elevation is in the smokers’ periodontitis group than in nonsmokers’ periodontitis and controls.\n\nTable 3 demonstrates that the mean salivary biomarker levels in individuals with stage III and IV periodontitis showed a non-significant difference, regardless of whether they smoked.\n\nAccording to the comparison between periodontitis smokers and nonsmokers, as illustrated in Table 4, the mean salivary biomarker levels showed a non-significant association (p>0.05) between stage III and stage IV.\n\nOn the other hand (Figure 4), demonstrates in graphs the comparison of the mean of salivary biomarkers between stage III and IV periodontitis of both smokers and nonsmokers groups.\n\nRegarding the Pearson Correlation Coefficient between stage III and IV periodontal parameters and the salivary biomarkers, there was a significant relationship (p<0.05) in stage III periodontitis between citH3 and CAL as well as between CALPRO and each of (PLI, PPD, and CAL), whereas in stage IV periodontitis, the correlation was significant only between MPO and CAL, as shown in Table 5.\n\n* Significant difference (p<0.05); r: coefficient correlation between -1 and 1; p: probability.\n\nConcerning the correlations between citH3 and CALPRO levels, a strong correlation was observed in the group of smokers with periodontitis, whereas the correlation of citH3 with ELA was strong in the group of nonsmokers with periodontitis, as illustrated in Table 6.\n\nBased on the relationship between salivary biomarkers and clinical parameters, this study found a strong association between BOP% and CALPRO in smokers with periodontitis. Moreover, there was a strong association between BOP and ELA, as well as between CAL and MPO in the nonsmokers periodontitis group, as shown in Table 7.\n\n* Significant difference (p<0.05), r: correlation coefficient between -1 and 1, p: probability.\n\nFigure 5 describes the linear correlation between citH3 and CALPRO levels in smokers periodontitis group, as well as between citH3 levels and ELA levels in nonsmokers with periodontitis. On the other hand, also describes the linear correlation between CALPRO and BOP%, ELA and BOP%, and MPO and CAL.\n\nPeriodontitis smokers and nonsmokers, according to receiver operating curve (ROC) data, had good accuracy in estimating salivary biomarker sensitivity and specificity in differentiating periodontitis from healthy periodontium, as shown in Figure 6.\n\nAdditionally, the area under the curve (AUC) values between smokers periodontitis and control for salivary citH3, ELA, CALPRO, and MPO were 0.991-1,000, and the AUC between periodontitis nonsmokers and control for the selected markers was 0.964-1,000 also between smokers and nonsmokers periodontitis group was 0.878-0.750, as shown in Table 8.\n\n* Significant difference, AUC: area under the curve.\n\n\nDiscussion\n\nThis study evaluated NETosis biomarkers in smokers and nonsmokers with periodontitis. The benefit of our case-control study was the use of multiple salivary biomarkers (citH3, ELA, CALPRO, and MPO), thus distinguishing between the biomarkers with the greatest impact on periodontitis groups. There are different factors that may increase the severity of periodontitis, one of which is cigarettes smoking.2–4 According to our findings, CALPRO was significantly elevated in the saliva of male smokers in the periodontitis group. Cardoso et al.32 found that the male sex plays a role in CALPRO in predisposing individuals to periodontitis. The current finding is in agreement with Wei et al.23 who attributed elevated CALPRO to the recruitment of neutrophils in the inflammatory periodontitis site, which acts as an innate immune defense, and also found that CALPRO is used as an antibacterial agent released highly from neutrophils in response to periodontal disorders. Brembach et al.33 reported that nicotine induced changes in the release of ROS, which is one of the defense mechanisms of neutrophils against inflammation, in addition to NET formation. Smoking has an enormous effect on the host response. However, the present study was consistent with a previous study,33 and showed an elevation of CALPRO in smokers. However, D’Haens et al.34 showed that the salivary level of S100A protein, one of the CALPRO components, is decreased in individuals with inflammatory disease, which leads to a decline in the host’s oral defense. Herein, our data revealed that there is a higher elevation of ELA in smokers with periodontitis than in nonsmokers with periodontitis and controls; the part of our study of increasing ELA production in smokers with periodontitis group was consistent with the study of Özkaca et al.35 Our study also agrees with another recent study by Tseng et al.,36 who found that ELA promotes the progression and pathogenesis of periodontal disease. Pauletto et al.37 disagreed with our findings, and found that ELA showed no significant change in smokers’ periodontitis and the level of ELA is increased in nonsmokers with periodontitis; therefore, more studies are needed to focus on the level of ELA in smokers with periodontitis. The other biomarker identified in this study was MPO. The current study detected higher elevation of the level of MPO in smokers with periodontitis; the current results were consistent with those of Omer et al.,38 who found that compromised periodontal inflammation in smokers may have increased the expression of MPO. Gattani et al.39 also showed the same increase in MPO level in smokers with periodontitis than in nonsmokers with periodontitis, as it is considered as an indicator of oxidative stress caused by cigarette smoke and increased level of inflammation in the progression of periodontitis. However, a pilot study conducted by Magán-Fernández et al.40 discovered that, without statistical significance, MPO expression was greater in periodontitis than in gingivitis. Additionally, this study found a significant elevation in citH3 levels in smoker with periodontitis compared with nonsmokers. This was consistent with a study by Okamato et al.20 which found that citH3 is increased in individuals at risk than in control subjects. Kim et al.9 agreed with our findings of histone elevation, which is highly associated with the presence of NETs and bone destruction, and that citH3 bears NET-associated posttranslational modification. Few studies have examined the effect of smoking on citH3 in periodontitis patients. A study performed by Hosseinzadeh et al.41 demonstrated that smoking-related diseases may be aggravated by nicotine in cigarette smoke, which then activates the production of NETs. In contrast, Magán-Fernández et al.40 reported that the expression of citH3 is higher in gingivitis than in periodontitis. Furthermore, the present study showed that the biomarkers were unable to differentiate between stage III and IV periodontitis groups. However, another recent study conducted by Mohammed et al.42 agreed with our finding that the concentrations of salivary biomarkers matrix metalloproteinase (MMP8 and 9) and tissue inhibitor of metalloproteinase (TIMP1) were not significantly different (p<0.05) among the various periodontitis stages. Interestingly, the present study noticed a strong correlation between CALPRO and most of the clinical periodontal parameters in stage III periodontitis, thus enhancing the hypothesis that this biomarker performs an essential function in the NETosis stimulation process of periodontal inflammation, the present study finding was in line with Wei et al.,23 who found that CALPRO is positively correlated with clinical periodontal parameters in generalized aggressive periodontitis, and that there is a positive correlation between citH3 and CAL in stage III periodontitis, which is consistent with the findings of Kim et al.,9 who found that citH3 is strongly associated with bone destruction. Moreover, MPO showed a positive correlation with CAL. Similarly, Polizzi et al.24 showed that generalized chronic periodontal disease is positively correlated with salivary MPO. There was a strong and positive association between citH3 and CALPRO in smokers with periodontitis. Our data also revealed a highly significant positive relationship between citH3 and ELA in nonsmokers’ periodontitis. The results of this study indicate that the elevation of citH3 in both periodontitis groups is indicative of the process of NETosis and increases inflammatory reactions, even if periodontitis risk factors are present, which emphasizes a possible interaction between neutrophil loss and the prevalence of autoimmune diseases. Elevation of these biomarkers in periodontitis smokers and nonsmokers aids in the external breakdown of pathogens that get stuck within NETs. A limitation of the current study is the high exclusion criteria proposed in the study. However, it provides additional specifications for our data. The novelty of this study is the limitation of studies that evaluated the effect of the citH3 NETosis salivary biomarker in smokers with periodontitis.\n\n\nConclusions\n\nThe selected salivary biomarkers (citH3, ELA, CALPRO, and MPO) were used to identify differences between healthy periodontium and periodontitis. All the chosen biomarkers were elevated in the smoker periodontitis group, and there was a statistically significant difference between smokers and nonsmokers with periodontitis compared to the controls. Smoking appears to have harmful effects, one of which is the downregulation of immunological responses to bacterial infection. On the other hand, it reduces the ability of neutrophils to respond to periodontal infection; therefore, smoking increases the biomarker levels in the smokers periodontitis group. The citH3, ELA, CALPRO, and MPO levels could not differentiate between stage III and IV smokers and nonsmoker periodontitis groups. There was a significant correlation between the salivary biomarkers citH3 and CALPRO in the periodontitis group and between citH3 and ELA in the nonsmoker periodontitis groups. Interestingly, the salivary biomarkers citH3, ELA, and CALPRO were positively correlated. All the selected salivary biomarkers increased in cases of periodontitis and were associated with neutrophil enzymes that mediate NETosis and are connected to the onset and progression of periodontitis.\n\n\nAuthor’s contributions\n\nConceptualization Ideas: all authors RAN and BHA designed and performed the manuscript. RAN collected the patients, samples, and provided clinical information. RAN, BHA, MG, and AAA performed the experiments and contributed to the statistical analysis, reviewing the work for clarity and originality. RAN, BHA, and supervision by BHA. The authors reviewed and provided their stamp of approval for the paper. All necessary conditions for authorship have been fulfilled, and all the authors agree that the manuscript conveys their honest work.\n\n\nConsent to participate\n\nFollowing a sequential presentation of the research purpose and methods, all participants signed an informed consent form. The samples that collected in this study were salivary samples and this study was conducted at University of Baghdad/College of Dentistry/Department of Periodontics after ethical approval with reference Number: 844, project number: 844823 in 15-10-2023 was obtained, and a written consent was taken from the participant.\n\n\nEthics and consent\n\nEthical considerations were essential during the conduct of this study, introduced by the World Medical Association’s Helsinki Declaration (WMA), after submission to the ethical committee at the Dentistry College/University of Baghdad to obtain ethical approval (Reference Number: 844, project number: 844823, date: 15-10-2023).",
"appendix": "Data availability\n\nFigshare: Evaluation of NETosis (Neutrophil Extracellular Traps) Biomarkers in Smokers and Nonsmokers Periodontitis Patients. https://doi.org/10.6084/m9.figshare.25997872.v2 43\n\nThe project contains the following underlying data:\n\n• 2=F1000=Data=Rasha Najim--InFormt.xlsx.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgment\n\nThe authors are grateful to all study participants.\n\n\nReferences\n\nGasner NS, Schure RS: Periodontal disease. StatPearls. StatPearls Publishing; 2023.\n\nShah R, Singh A, Singh HM, et al.: Effect of tobacco smoking on the periodontal health in Parsa, Nepal: A comparative cross-sectional study. J Oral Res R. 2024 Jan 1; 16(1): 1–5. Publisher Full Text\n\nKnie LV, Leknes KN, Xue Y, et al.: Serum biomarker levels in smokers and non-smokers following periodontal therapy. A prospective cohort study. BMC Oral Health. 2024 Apr 16; 24(1): 463. 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Publisher Full Text\n\nTseng HY, Chen YW, Lee BS, et al.: The neutrophil elastase-upregulated placenta growth factor promotes the pathogenesis and progression of periodontal disease. J Periodontol. 2022 Sep; 93(9): 1401–1410. PubMed Abstract | Publisher Full Text\n\nWei L, Liu M, Xiong H: Role of calprotectin as a biomarker in periodontal disease. Mediat Inflamm. 2019 Aug 21; 2019: 1–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPolizzi A, Torrisi S, Santonocito S, et al.: Influence of myeloperoxidase levels on periodontal disease: An applied clinical study. Appl Sci. 2020 Feb 4; 10(3): 1037. Publisher Full Text\n\nTonetti MS, Greenwell H, Kornman KS: Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol. 2018 Jun; 89: S159–S172. 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Publisher Full Text\n\nMitani A, Matsuura T, Aino M, et al.: Effectiveness of novel oral hygiene instruction avoiding in attentional blindness using an application for unique plaque control record calculation: A randomized clinical trial. J Periodontal Res. 2024 Jan 8; 59: 458–467. PubMed Abstract | Publisher Full Text\n\nAllen P, Bennett K, Heritage B: SPSS Statistics version 22: A practical guide. 3rd ed.Cengage Learning Australia Pty Limited; 2014. Reference Source\n\nCardoso IL, Nieto Medina D: Genetic and environmental factors involved in the development of periodontal disease. European J Bio Pharma Sci. 2019; 6(7): 403–414.\n\nBrembach TC, Sabat R, Witte K, et al.: Molecular and functional changes in neutrophilic granulocytes induced by nicotine: a systematic review and critical evaluation. Front Immunol. 2023 Nov 23; 14: 1281685. PubMed Abstract | Publisher Full Text | Free Full Text\n\nD’Haens G, Ferrante M, Vermeire S, et al.: Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis. 2012 Dec 1; 18(12): 2218–2224. Publisher Full Text\n\nÖzçaka Ö, Bıçakcı N, Pussinen P, et al.: Smoking and matrix metalloproteinase, neutrophil elastase and myeloperoxidase in chronic periodontitis. Oral Dis. 2011 Jan; 17(1): 68–76. PubMed Abstract | Publisher Full Text\n\nTseng HY, Chen YW, Lee BS, et al.: The neutrophil elastase-upregulated placenta growth factor promotes the pathogenesis and progression of periodontal disease. J Periodontol. 2022 Sep; 93(9): 1401–1410. PubMed Abstract | Publisher Full Text\n\nPauletto NC, Liede K, Nieminen A, et al.: Effect of cigarette smoking on oral elastase activity in adult periodontitis patients. J Periodontol. 2000 Jan; 71(1): 58–62. PubMed Abstract | Publisher Full Text\n\nOmer-Cihangir R, Baser U, Kucukgergin C, et al.: Impact of smoking on neutrophil enzyme levels in gingivitis: a case-control study. Int J Environ Res Public Health. 2021 Jul 30; 18(15): 8075. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGattani D, Sahu J, Kar N, et al.: Salivary profile of matrix metalloproteinase-8, tissue inhibitors of matrix metalloproteinase-1, myeloperoxidase, and nitrous oxide in smokers versus nonsmokers with chronic periodontitis. J Int Clinical Dent Res Org. 2021 Jul 1; 13(2): 118–123. Publisher Full Text\n\nMagán-Fernández A, O’Valle F, Abadía-Molina F, et al.: Characterization and comparison of neutrophil extracellular traps in gingival samples of periodontitis and gingivitis: A pilot study. J Periodontal Res. 2019 Jun; 54(3): 218–224. PubMed Abstract | Publisher Full Text\n\nHosseinzadeh A, Thompson PR, Segal BH, et al.: Nicotine induces neutrophil extracellular traps. J Leukoc Biol. 2016 Nov; 100(5): 1105–1112.\n\nMohammed HA, Abdulkareem AA, Zardawi FM, et al.: Determination of the accuracy of salivary biomarkers for periodontal diagnosis. Diagnostics. 2022 Oct 14; 12(10): 2485. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNajim R: 2=F1000=Data=Rasha Najim.xlsx. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "315884",
"date": "09 Sep 2024",
"name": "Zerina Hadzic",
"expertise": [
"Reviewer Expertise Periodontal disease",
"Salivary biomarkers",
"Oxidative stress",
"Inflammatory biomarkers",
"Biofilm."
],
"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 text of the research article titled: Evaluation of NETosis (Neutrophil Extracellular Traps) biomarkers in smokers and nonsmokers periodontitis patients requires major correction. The abstract is not clear and it does not give all the important details for understanding the research article, especially in the methodology section. From the title, abstract, but also Introduction it is not clear that the authors aimed to determine the salivary parameters only in male patients. It is also not elaborated clearly why the female patients were excluded. The introduction does not give any inside in the other similar studies and the background for their examination in patients with periodontitis. The classification of the patients in the stage III and IV periodontitis groups is not correct. Stage III and stage IV in the segment of bone loss are radiologicaly with bone loss to mid-third of root or beyond, but are separated by the number of teeth lost, and with complexity of stage III being applicable to stage IV and additional complexity including masticatory disfunction, bite collapse, drifting, flaring and less then remaining 20 teeth (10 opposing pairs). [ ref 1 ] Also it is not clear if the patients consumed and antioxidants and if this was an exclusion criteria applied. In the saliva sampling section it is not clear: did the patients brush before the sampling? how were samples defrosted? Also the time frame of saliva sampling is not clear. The authors state: Salivary samples were conducted between 9 am and 12 pm. Is the 12 pm: noon or 00:00, since by definition noon is neither AM or PM. Also, study included PLI in 3rd molars but excluded the 3rd molar for other clinical periodontal indices. Were the 3rd molars included in the determination of periodontitis stage? Conclusion is not written clearly and does not correspond to the precise results and study groups.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "328722",
"date": "30 Oct 2024",
"name": "Amal Bouziane",
"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 study tries to give some evidence about variations in salivary biomarkers’ (Neutrophil Extracellular Traps) levels in smokers and nonsmokers periodontitis patients. The comparison also concerned periodontally affected patients versus control subjects with a healthy periodontal status. Authors try to bring support to the clinical accuracy of NETosis salivary biomarkers to differentiate periodontitis groups (smokers and nonsmokers) from controls. However, the manuscript has many methodological and redactional flaws and requires improvement. The main issue is related to the design of the study and the presentation of the results.\nTitle:\n\nAs NET is a production of NETosis, the abbreviation in the title should be reviewed. Please precise that periodontitis is a stage III and IV periodontitis.\n\nIntroduction:\n\nPhysiopathology and risk factors of periodontitis need more clarification. Genetics should not be considered as a local factor. The sentence “ .. severe periodontitis is caused by a lack of neutrophils, and an excess of neutrophils appears to be harmful..” seems to be contradictory. Idem for “..The primary defense of periodontal tissues is provided by NETs, and a deficiency in NETs can result in severe early-onset periodontitis. Smoking cigarettes accelerates the production of NETs and PMN-derived proteases, which are responsible for breaking down connective tissue..”. Please clarify. Please add text to abbreviations at the first time.\n\nMethods:\n\nThe main issue is related to the design of the study. It is not clear if case is Periodontitis group and control is Non periodontitis group, Or case is smokers group and control is Non smokers group. The outcome conditions the sample size and the selection of the study population. Periodontitis cases, including smokers and nonsmokers, should be compared with non-periodontitis controls including smokers and nonsmokers. Please avoid redundancy in the study design. “..not clinical trial study” could be removed. Please review the case definition of periodontitis according to EFP and AAP 2017 consensus criteria. What do the authors mean by “ any periodontal treatment” in Exclusion criteria? Rarely, a patient did not receive a periodontal treatment in the past, at least a periodontal scaling. Smoking was a main exposition in the study. Smoking could not be an exclusion criterion. Please give a sharp Flow Chart, and add participants with healthy periodontal status. Why the pilot study was conducted? Please explain its part in the methods.\n\nResults:\n\nThe “increase” of parameters implies a prospective design study. Please give an appropriate word. Idem for elevation. The Statistical analysis “Two qualitative variables, distributional correlations, were tested using the chi-square test.” Should be clarified. It is more appropriate to focus results to the objectives of the study. Figures 2 and 3 contain repeated information. They could be removed. 0.000 should be replaced by <0.001 for the p value. Indicate the abbreviations under the tables (for example table 5) Please begin the paragraph “Salivary biomarkers levels” with text. Present the most relevant graph in Figure 5. The first paragraph of ROC results should be reformulated. The accuracy of a diagnosis test needs a different method to state of Diagnostic accuracy of NETosis biomarkers.\n\nDiscussion:\n\nHow the absence of correlation between CAL and Histon-H3, in stage IV, could be explained comparatively to stage III? (see Table 3)\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?\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": []
}
] | 1
|
https://f1000research.com/articles/13-907
|
https://f1000research.com/articles/13-904/v1
|
07 Aug 24
|
{
"type": "Research Article",
"title": "Stage 2 Registered Report Personal factors and group creative outcomes: A correlational meta-analysis",
"authors": [
"Adrien A. Fillon",
"Fabien Girandola",
"Nathalie Bonnardel",
"Jared B. Kenworthy",
"Lionel Souchet",
"Fabien Girandola",
"Nathalie Bonnardel",
"Jared B. Kenworthy",
"Lionel Souchet"
],
"abstract": "Previous research has indicated that individual differences play a role in group creativity. Group creativity activities have different outcomes, leading to numerous ways to assess the effectiveness of these creative activities. To date, no meta-analysis has been performed on the relationship between the outcomes of the creative activity and personal factors of the group members. In this Registered Report, we conducted a meta-analysis (n = 11, k = 72) on the relationship between personal factors and group creativity outcomes. We found weak support for a positive correlation between self-efficacy and group creativity outcomes, between r = .04 and r = .67. We found weak support for a moderation effect of time constraint, with stronger relationships for conditions limited to 20 minutes as opposed to 10 minutes. Finally, we found that only a few studies could be included in the meta-analysis, because many studies (1) did not directly measure creativity, or (2) measured other, less common personal factors. We call for a more systematic and direct approach to measuring creativity and an improvement of open science practices in the field. Data and analysis can be found at https://osf.io/xwph9.",
"keywords": [
"brainstorm",
"creativity",
"meta-analysis",
"personality",
"correlation"
],
"content": "Personal factors\n\nExtensive research has been conducted on personal factors influencing individual creativity, but less research has been done on people in social contexts (Reiter-Palmon & Kaufman, 2018). Creativity was first investigated as an individual process, and teamwork was considered as a facilitator or inhibitor of individual creativity (Amabile, 1996; Reiter-Palmon et al., 2012). Today, team creativity is central to product design and development, and to the solution of challenging problems. Understanding how each member of the creative group can have a different impact on the outcome of creative thinking is crucial since it can contribute to improving the process and customizing the creative activity for the participants.\n\nFor a long time, the empirical literature examining creativity activities mostly associated personal factors with personality traits (Barron & Harrington, 1981; McCrae & Costa, 1995; Puryear et al., 2017; Yao & Li, 2021). Recently, researchers have started examining the effects of emotional disposition and cognitive differences to get a broader comprehension of individual differences and their contribution to group creative outcomes.\n\n\nRelationships between personal factors and group creativity outcomes\n\nThere is a growing interest in the link between personal factors and group creativity outcomes. Many existing studies have been conducted regarding the personal factors involved in fluency and flexibility (Butler et al., 2003), originality and usefulness (Baer et al., 2008), and number of ideas (Brown et al., 1998). However, there have been debates regarding the relationship between personal constructs and group creativity outcomes due to mixed findings. Coursey et al. (2018) provided a review of individual factors in group creativity activities. In their overview, they stated (p. 26-27):\n\n“It is presumed that there will be some degree of similarity between the effects observed for individuals and groups. However, we have highlighted a number of ways in which the effects of individual differences may not be simply additive. […] Thus, in agreement with the configural perspective of Moynihan and Peterson (2004), certain team compositions may be ideal for groups that go through the full phases of the creative process. One strategy would be to compose a team that had the ‘right mixture’ for the multiple phases, or one could compose separate teams specifically for different phases.”\n\nIndeed, in a group setting, some social traits can improve creativity potential, for example, traits leading group members to be more attentive to the ideas of others, to process the shared ideas including the more radical ones, to be more motivated and persistent in the search for new ideas, to build on the ideas of others, and to share new ideas. We have summarized the list of personal factors we considered in this meta-analysis in Table 1.\n\nTo point out important findings in the literature, Feist (1998) asserted that creative individuals need to balance between social stimulation and quiet reflection. Therefore, extroverted people may show better creative performance in some groups, depending on the need to interact with others (see also Anderson et al., 2008). Conscientiousness, which leads people to adhere to norms and rules (Roberts et al., 2009), may help generate a high number of ideas, but not necessarily ideas that are original or useful. This idea is supported by Feist (1998), who found that artists, who need to develop original ideas individually, were generally low in conscientiousness. Agreeableness is a strong predictor of team performance because it is related to trust and morale (Hogan et al., 1994). However, creative people are generally low in agreeableness (Bechtoldt et al., 2012; Karwowski & Lebuda, 2016). Low neuroticism could be a more beneficial trait to have in a group creativity setting (Bell, 2007; Da Costa et al., 2015; Peeters et al., 2008). Other personal factors can have differential links with various creativity outcomes. Emotional factors can play a role (Kuška et al., 2020), such as anxiety (Camacho & Paulus, 1995), and emotional intelligence (Wang, 2015). It is also the case for cognitive dispositions such as cognitive orientation or cognitive styles (Brown et al., 1998), and other cognitive traits such as creative self-efficacy (Taggar, 2019; Tierney & Farmer, 2002), epistemic motivation (Bechtoldt et al., 2010), Need for Closure (Chirumbolo et al., 2004, 2005), and Need for Cognition (Wu et al., 2014). For example, Need for Closure, a cognitive tendency to avoid ambiguity, is related to the quality of ideas generated but not originality (Watts et al., 2017). Most studies mentioned above examined the relationships of interest at the individual level. At the time of writing, there is no literature review or meta-analysis on the relationship between personal factors and creativity outcomes in a group setting.\n\n\nResearch aims and Hypotheses\n\nIn this study, we sought to examine: (1) the overall relationship between personal factors and creativity outcomes in group settings; and (2) moderators of these relationships.\n\n\nModerators\n\nWe examined different moderators in the relationships between personal factors and group creativity outcomes, including environmental influence on how the activity was conducted, tasks factors related to the rules of the creative activity, and personal factors such as demographic variables. Our moderator hypotheses were exploratory and mostly based on the last review available on the subject (Coursey et al., 2018). In this review, researchers indicated that there were very few studies on the subject, and we expected some moderators to be untestable meta-analytically in the absence of primary-level empirical data. We explored and reported all available relationships. In italics below are the hypotheses for which the literature on the subject tends to provide evidence for a relationship.\n\nFamiliarity\n\nFamiliarity with the group is the extent to which group members know each other (Sosa & Marle, 2013). For example, familiarity can range from participants who do not know each other in a laboratory setting to teammates who have already worked with each other for a long time. In the study conducted by Sosa and Marle (2013), it was found that the more familiar group members are to one another, the better the creative outcomes. We hypothesized that individuals who struggle with novelty will produce better group creativity outcomes if they are familiar with the other group members. These groups include participants high in introversion (Orengo Castellá et al., 2000), Need for Closure (Chirumbolo et al., 2004), and social anxiety (Camacho & Paulus, 1995).\n\nFamiliarity: In a non-familiar context, introversion, need for closure and social anxiety are negatively associated with creative outcomes. In a familiar context, the negative correlations are weaker than in a non-familiar context.\n\nSkill and knowledge diversity\n\nThe idea behind skill diversity is similar to familiarity: people who are closer to each other tend to bond easier, leading to less perceived stress and a more positive social climate, resulting in better creative outcomes. At the same time, synergy can be difficult in an overly homogeneous group, because not every member adds creative value beyond the others (Nijstad & De Dreu, 2002). A group with members who have substantial overlap in skills and knowledge may have limited creativity due to a lack of diversity. We exploratively tested the moderation hypothesis that skill and knowledge diversity in a group modifies the relationships between personality traits and creative outcomes.\n\nGroup demography\n\nDiversity with respect to hierarchical status, gender, age, and field of study, leads groups to be more creative (Choi, 2007; Paulus & van der Zee, 2015). In small groups, and using electronic brainstorming, research indicated that groups composed of women showed greater fluency (i.e., produced more ideas) than mixed groups, groups composed of men, or “solo” groups (Peter et al., 2021). For group creativity, competition had a positive effect on creative outcomes for groups composed of men, but a negative effect for groups composed of women (Baer, 2013). We explored the hypothesis that group demography modifies the relationships between personality traits and creative outcomes.\n\nConstraint\n\nConstraint refers to the degree of freedom in creative activity. Two major types of constraints can be implemented in brainstorming activities: production blocking, which prohibits members from sharing their ideas as they come to mind, and asynchrony, which means that participants generate ideas individually before sharing them with each other. In the production blocking condition, individual factors are less important for creativity (Nijstad & Stroebe, 2006) than in the non-production blocking condition, whereas in the asynchronous condition, individual factors are more important than in the synchronous condition (Paulus & Kenworthy, 2018).\n\nConstraint: In a production blocking setting, the relationships between individual factors and creative outcomes are lower than in a non-production blocking setting.\n\nIn an asynchrony setting, the relationships between individual factors and creative outcomes are higher than in a synchrony setting.\n\nType of task\n\nThe type of task can influence the relationship between personal factors and creative outcomes. In conjunctive tasks, creative tasks in which participants pass ideas from one to another, the performance of the group is most strongly influenced by persons with traits that are highly positively or negatively related to creative outcomes. In disjunctive tasks, where participants share ideas before their selection, the influence of each individual is weaker because they do not influence the sharing process (Coursey et al., 2018). We explored the evidence for an effect of this type of task in creative processes.\n\nType of task: In disjunctive tasks, the relationships between personal factors and creative outcomes are smaller in magnitude (regardless of sign) than in conjunctive tasks.\n\nCreative phase\n\nHarvey (2013) found that the diversity of ideas was positively related to divergent creativity (i.e., the mental process leading to producing ideas that are different, varied, and original), and negatively to convergent thinking (i.e., the mental process leading to narrowing the set of ideas generated towards a solution). Furthermore, convergent thinkers performed better in the convergent phase than in the divergent phase; divergent thinkers performed better in the divergent phase than in the convergent phase. As hypothesized by Coursey et al. (2018), introverts could be better at building and integrating creative ideas in the convergent phase, while extroverts could be less inhibited and make more contributions during the divergent phase.\n\nCreative phase: Divergent thinking and extraversion are more strongly and positively associated with creative outcomes in the divergent phase than in the convergent phase.\n\nConvergent thinking and introversion are less negatively associated with creative outcomes in the convergent phase than in the divergent phase.\n\nNumber of participants\n\nThe number of group members is critical in creating, sharing, and transforming ideas and information into projects. The number 5 is generally admitted as optimal in terms of maximizing interacting group performance (Steiner, 1972). As the number increases, the creative performance of the group decreases (Fellers, 1989). The problem is that, as the number of participants increases, the likelihood of dysfunctional behaviors also increases (i.e., dominance by individual members, fear of personal evaluation, fear of speaking in public, pressure for conformity, and task restrictions, see Fellers, 1989). For personal factors, the number of participants might “dilute” the creative contribution of each member, leading to a weaker (positive or negative) relationship. Dugosh et al. (2000) also found that high levels of off-task communication were detrimental in face-to-face brainstorming groups, and that off-task communication increases with the number of participants (particularly extrovert participants).\n\nNumber of participants: the higher the number of people who participate in the activity, the weaker the (negative or positive) relationships between personal factors and creative outcomes.\n\nTime pressure\n\nThe possibility to create and share information depends on the time available. Most creative tasks are structured and time-limited, mostly because creativity is mentally effortful. Time limitation is detrimental to group creativity (Karau & Kelly, 1992). Chirumbolo et al. (2004) found that time pressure reduced the percentage of creative acts during a group discussion and was positively related to personal need for closure (both reduced creative outcomes).\n\nTime pressure: the negative relationship between need for closure and creative outcomes in group creativity is stronger under time pressure than under no pressure.\n\nLeadership\n\nIt is challenging to assess how the leadership type will influence the relationship between personal factors and creativity. We decided to split leadership into two traditional types: transformational and transactional. In transformational leadership, the leader clearly states the goal and pushes the group toward attaining this goal. In transactional leadership, the leader relies on an exchange process in which group members are rewarded for accomplishing specific goals (Jung, 2001; Mumford et al., 2019). Research has found that transformational leadership leads to higher creative outcomes than transactional leadership (Jung, 2001; Sosik & Cameron, 2010; Zhang et al., 2011). Sosik and Cameron (2010) indicated that transformational leadership was related to an increase in motivation to create more ideas and ideas that are more original. On the contrary, Taggar (2019) explained that a cohesive team might follow the dominant actors in the team instead of trying to find more ideas. Thus, he hypothesized that excessively strong cohesion in a team following a (transformational) leader could impair creative collective efficacy. Anderson and Fiedler (1964) also showed that groups with participatory leaders (i.e., transactional leaders) had the highest number of ideas generated, and groups with supervisory leaders had the most original and useful ideas. We hypothesized that the leadership type has an effect on the relationship between personality and creative outcomes. Leaders close to the team who create a non-judgmental climate could help improve the performance of anxious, introverted, and less motivated members. On the other side, leaders with a more distant relationship with the group, in the exchange process to attain the goal and who do not contribute to the task, could reduce the performance of these members, reducing the global creative performance. We explored the hypothesis that the type of leadership influences the relationships between personality traits and creative outcomes, leading to giving more weight to the indication from Sosik and Cameron (2010) that transformational leadership leads to a stronger positive link or to the explanation of Taggar (2019) that transactional leadership leads to a stronger positive link.\n\nPublication status\n\nWe examined publication status for possible moderating effects on the relationship between personal factors and creativity outcomes. Several recent meta-analyses (Mathur & VanderWeele, 2020; Moreau & Gamble, 2020; Schmucker et al., 2017; Vosgerau et al., 2019) have suggested that including unpublished work can help improve the capture of the ‘true’ effect size. Accordingly, we expected that studies that were published are likely to report stronger associations than those that remained unpublished.\n\nPublication status: published studies report stronger negative and positive relationships than unpublished studies.\n\n\nMethods\n\nWe shared all procedures, materials, datasets, and analysis code on the Open Science Framework (https://osf.io/xwph9/). The pre-registration and additional information about decisions are available in the supplementary materials of the extended data. We deviated from Stage 1 with the following: We did not use Scopus because we were not able to access it. We modified keywords during the literature search to have more results, as our first search was too restrictive. Finally, we have not conducted all publication bias tests mentioned, and the cumulative test because of the lack of studies to conduct them.\n\nPersonal factors are explained in Table 1. They consist of personality traits: 1) openness, 2) conscientiousness, 3) extraversion, 4) agreeableness, 5) neuroticism; emotion: 1) social anxiety and 2) emotional intelligence; cognition: 1) Cognitive style, 2) epistemic motivation, 3) self-efficacy, 4) need for closure, 5) Need for Cognition. The three categories of creative outcomes are 1) number of ideas generated, 2) originality of these ideas and 3) usefulness of the ideas.\n\nStudies including personal factors (see Table 1) and measuring creative outcomes in group settings are included in our analysis.\n\nDatabase searches. To identify articles that are potentially relevant to our topic of investigation, we conducted searches using Google Scholar, Psychinfo, Web of Science - social science citation index, Proquest- dissertations and theses (for suitability, see Gehanno et al., 2013; Martin-Martin et al., 2019; Moreau & Gamble, 2020).\n\nFor personal factors, the keywords were personality trait*, openness, extraversion, introversion, conscientiousness, agreeability, neuroticism, anxiety, social anxiety, thinking style, convergent thinking, divergent thinking, Need for Closure, creative self-efficacy, epistemic motivation, Need for Cognition, emotional intelligence. For creative outcomes, the keyword was simply “creativity.” Initially, we had planned to use more specific search terms (such as “number of ideas”); however, this led to very few results which prompted us to switch to a broader search strategy. All search patterns included the following operators: “group*” OR “team” AND “correlation”.\n\nDuring the search, keywords related to constructs were linked with the Boolean logic operators “OR” and keywords between construct 1 and construct 2 with “AND”. Variations of the keywords were included in the search with the original keywords if search results yielded fewer than 100 results, linked with “OR”. (e.g., “personality trait*” AND “useful*”). More information on the search pattern process can be found in the coding sheet under the tab “search pattern.” Database searches for each search pattern were terminated after combing through 30 records consecutively without potentially relevant papers for the inclusion criteria.\n\nThe search included papers listed under the “related articles” and “cited by” features in Google Scholar to identify papers that are similar or have cited the identified articles. We looked at other articles that were published by identified authors in the field to check if there were relevant papers that we may have missed. We systematically contacted the authors of the identified articles (see the pre-registered email template in the supplement) and issued a call for unpublished findings on ResearchGate and Twitter to find relevant unpublished data. For all the articles, titles, abstracts, tables, and methods sections were scanned to identify the relevance of a source.\n\nCorrelational meta-analyses typically exclude studies that manipulated the target variable prior to measurement (e.g., Chevance et al., 2019), or alternatively conduct a separate meta-analysis for studies with manipulations or interventions (e.g., Schmitt et al., 2014; van Kleeck et al., 2010). First, we decided to restrict our meta-analysis to correlational studies that measure personal factors in creative contexts. Studies were excluded if they 1) experimentally manipulated an independent variable related to personal factors (e.g., manipulated motivation, social climate and anxiety, information and Need for Closure, etc.), 2) failed to report the crucial statistics necessary for a meta-analysis (i.e., correlation coefficient or other effect sizes that can be transformed into correlation coefficient, sample size), or 3) were not written in English or French unless all necessary information was provided in English or could be obtained from the authors.\n\nStudies that met our criteria were coded into the “Searched articles” tab within the coding sheet. Articles were scanned to determine whether they should be included into the main coding sheet or not. Reasons for exclusion were documented. Authors of studies with missing statistics were contacted for relevant datasets/information through the “contacting author” tab and the corresponding mail template (see supplementary material). If the dataset was provided, we included the article in the main coding tab. Finally, the PRISMA diagram in Figure 1 and the included studies in Table 2 summarize how and which studies were included.\n\nExtracted data from the included studies were recorded in the “main coding sheet” tab. When available, the main correlations between personal factors and creative outcomes were recorded, along with intercorrelations between creative outcomes, the type of scale used, sample demographics, and publication information. Moderator variables were coded in a separate column in the main coding sheet.\n\nWe developed a Rmarkdown Script for the statistical analyses. The packages used are indicated in the supplementary material. Our main package for meta-analysis is Psychmeta (Dahlke & Wiernik, 2019). We used Pearson’s correlation coefficient r as the main indicator of effect size. Whenever available, we used correlations obtained directly from authors of original papers. If only regression results were available, we converted to correlation by using a transformation provided in the supplement. If not possible, we asked the authors to provide either the correlation or raw data. Correlations were corrected for attenuation by using the formula (Dahlke & Wiernik, 2020):\n\nGiven the range of different outcomes for each category, we expected the heterogeneity in the sample to be relatively high. Thus, a random effect model was used for all relationships. Split conditions due to moderators were collapsed to allow for comparison of the relationships. All conversions and coding decisions were documented. A meaningful association is expected as having a correlation of at least r = .10 (Cohen, 1988; Gignac & Szodorai, 2016; Schäfer & Schwarz, 2019). We documented all conversions and coding decisions. We included the original quotes and/or table/page numbers from the original articles into the coding sheet to facilitate reproducibility. We plotted forest plots presenting the correlation for every relationship. We presented the relation with confidence intervals and the sample size of each study.\n\nStatistical heterogeneity between studies was determined using an 80% credibility interval (as used in Borenstein et al., 2009; Wiernik et al., 2017). Wiernik and Kostal (2019) explained how the credibility interval performed better than the most used Q significance test. The main reasons are that the Q test is underpowered in most situations and that it confounds the sample size of studies and the magnitude of effects found in the studies. Finally, Paterson et al. (2016) suggested thresholds for credibility intervals as an indication for moderation (e.g., corrected correlations < .15 as negligible, .15–.24 as small, .25–.39 as moderate, and ≥ .40 as large). If there was indeed meaningful heterogeneity, we explored potential moderators. Our design for the analysis is shown in Table 3.\n\nExploratory analyses\n\nInitially, we had planned to include additional possible moderators that emerged during the literature search. Due to the low number of studies, such additional exploratory analyses were not possible.\n\nPublication bias\n\nTo address possible biases, we corrected for sampling error and measurement error, as indicated in the guidelines for psychometric meta-analyses (Schmidt & Hunter, 2015). Reliability was corrected using internal consistency artifact distributions (alpha or composite reliability) compiled from studies included in the present meta-analysis. A summary of weighted mean internal consistency can be found in the supplementary materials. We had originally planned to conduct a sensitivity analysis (Mathur & VanderWeele, 2020) with the use of cumulative meta-analysis but could not do so due to the lack of studies.\n\nFinally, we conducted a PET-PEESE analysis (Stanley & Doucouliagos, 2014) and a p-curve analysis (Simonsohn et al., 2014).\n\n\nResults\n\nMeta-analytic results are shown in Table 4. There were 25 combinations, and for 12 of them (48%), only one effect size was available, making it impossible to perform a meta-analysis. Of the studies available for meta-analysis, only three constructs suggest a positive non-zero relationship: the relationship between creative self-efficacy and the number of ideas generated (ρ = .35, 95%IC [.04, .67]) the originality of ideas (ρ = .35, [.09, .60]), and the usefulness of ideas (ρ = .49, [.33, .65]).\n\nDue to the extremely small number of effect sizes, it was not possible to analyze all moderators. Table 5 summarizes the moderator data.\n\nIn particular, only one moderator is significant, the effect of time (β = 0.01, p = .01). However, the β estimator is small and indicates that each minute spent in the creativity session increases the relationship between personal factors and creative outcomes by r = .01. Additionally, the residual heterogeneity test is significant, indicating that other uncaptured moderators are at work (Q = 382.19, p < .001).\n\nThe inter-correlations between the creative outcomes provide no evidence for a relationship between the number of ideas and originality (7 studies, ρ = -.01, [-.30, .29]), a positive relationship between the number of ideas and usefulness (2 studies, ρ = .67, [.670, .674]), and originality and usefulness (2 studies, ρ = .47 [.10, .85]). For the personality traits, 4 studies found a weak relationship between openness and extraversion ρ = .18, [.02, .33] (see Table 6).\n\nWe created a sunset plot in Figure 2 to display the statistical power of studies included in the meta-analysis. The average power is 13.5% and the replicability index 0% which means that we have no chance to reject H0 when there is a true effect, and no chance at all to replicate one study given the median average power of studies included in the meta-analysis and success rates of these studies (see Motyl et al., 2017 for R-index).\n\nTable 7 presents the mean reliability scale of all variables included. The reliability was high across all variables, between.75 and.91.\n\nThe PET-PEESE analysis was not significant (PET: t = 1.95, p = .06; PEESE: t = 1.85, p = .07). In particular, the average correlation found by the PET test is r = -.17 [-.40, .06] and by the PEESE test r = -.06 [-.18, .06] which indicates an effect size close to 0 with a tendency to be rather negative.\n\nThe p-curve test indicated no signs of unpublished non-significant results (see Figure 3). It also indicated a statistical power of 93% [0.88, 0.97]. However, in the case where there are few effect sizes and strong heterogeneity, the p-curve test is not reliable (van Aert et al., 2016).\n\nRegarding the cumulative analysis, it was not possible to perform it because of the too small number of studies included in the analysis (< 20).\n\n\nDiscussion\n\nThis meta-analysis investigated the links between personal factors and group creativity. The results are limited, given the very few studies and thus the very few effect sizes we could include. We found support for only one relationship, positive, between self-efficacy and all three creativity outcomes: the number, originality, and utility of ideas.\n\nThese results, although disappointing, are not so surprising. In 2018, Coursey and colleagues wrote (p. 2-3): “Whereas many studies have examined the role of individual differences in individual creativity, relatively few have examined the role of individual differences in group and team creativity.” A little further on, they concluded (Coursey et al., 2018, p. 26): “We have provided an overview of how individual difference factors may influence group creativity. Much of this is based on the literature concerning individual differences in individual creativity. It is presumed that there will be some degree of similarity between the effects observed for individuals and groups.”\n\nOur systematic review confirms that the majority of studies are based on individual creativity, as we found only 11 studies to include in our meta-analysis. Focusing on the creativity side, out of the 758 articles selected—with the criterion requiring the exact term “group” or the exact term “team” to be mentioned—160 studies concerned individual creativity, creative personality, perception of being creative, creative potential, or creative intelligence. Furthermore, when selecting the most used indicators in the creativity literature (number, originality, and usefulness of ideas), we found that the majority of studies did not measure group creativity with these indicators.\n\nSeventy-two studies measured perceived creativity, whether by other team members or by the manager. In most of these studies, creativity was measured by Zhou and George’s (2001) 13-item scale, an example of which is “the team/team member suggests new ways to achieve goals or objectives” or “the team/team member often has new or innovative ideas”. The scale has not been psychometrically evaluated and there seems to be no evidence of a link between the scores on this scale and the actual creativity of individuals. We have not found any studies that measured both perceived creativity with this scale and group creative outcomes. In addition to this measure, about 20 studies measured ‘general team performance’, asking a question about creativity in this performance, or about creative decision-making in a team, but then measured only the choice made by the team. In contrast, direct measures of creativity were much rarer. This could be because such measures require experts in the creative area who can code ideas according to the indicators used (numbers, originality, and usefulness of ideas). Finally, despite the selection criteria, 181 results were not about creativity or did not measure it, with the word “creativity” being mentioned in the introduction or discussion of the study.\n\nFurthermore, there was a small number of studies that manipulated individual factors, for example by measuring personality traits prior to experimentation, and by creating groups by separating individuals according to their level (low or high) on a personality trait. Others measured, for example, optimism, individualism, temperament, depression, envy, critical thinking, or self-constructs. In total, these exclusion criteria applied to 136 studies. It would be possible to conduct an experimental meta-analysis on the subject, which would not measure the relationship between individual factors and group creativity but the impact of a particular personality trait on group creativity. However, the results could be as disparate and inconclusive as in this meta-analysis, as other exclusion criteria would apply. Indeed, many of these studies also included only measures of perceived creativity, measures of individual creativity, and some were qualitative in nature. Thus, it is not clear that a meta-analysis of this type would provide enough effect sizes to conduct an informative analysis.\n\nOut of the 11 studies included, 1 is from 2019, and 3 are from 2020, a sign that personality factors and group creativity are currently being investigated. In this sense, it is possible that this meta-analysis came a bit too early compared to the primary studies on the subject.\n\nTime limit\n\nThe moderator analysis revealed a possible weak effect of time on the relationship between personal factors and creativity outcomes, as each minute spent in the creativity session increases the relationship between personal factors and creative outcomes by r = .01. However, given the limitation of the data, we could not test the hypothesis on cognitive closure. Most of the studies included in the analysis had a time constraint between 5 and 10 minutes, and for these studies, the moderation analysis revealed no effect. The effect of time limit was found for the studies comparing 10 and 20 minutes; the relationships were systematically stronger for the 20 minutes than for the 10 minutes condition. This finding suggests that a longer session leads to a stronger possibility for participants to express their individuality in group creative tasks, at least up to 20 minutes. We are limited in the generalizability of our findings, as the relationships were only found for 5 associations relating self-efficacy to originality/usefulness.\n\nThe results of this meta-analysis may help to improve the field of research linking creativity and personality.\n\nFirst, we built on the conjecture of Coursey et al. (2018) and improved current knowledge by systematically quantifying the data on the subject. We found that the available data was limited. Very few studies measure group creativity. Most studies measure perceived creativity, through questionnaires and surveys, and some studies make up their own measures of creativity, according to their own criteria. It would be possible to improve our knowledge of group creativity by using standardized creativity methods and protocols and by using direct measures, especially as in the majority of the studies included, inter-expert reliability was high, indicating that the perception of creativity is shared among experts.\n\nOnly one personal factor had a positive relationship with the three group creative outcomes: self-efficacy. This is not surprising, as self-efficacy is one of the most widely used individual factors in psychology. For example, the book Self-efficacy: The exercise of control (Bandura, 1997) is cited 108 314 times on Google scholar (December 2022). The other social, cognitive, and emotional factors seem to be less studied or not studied in correlational studies. Surprisingly, many studies reported some personality traits, but not all. In the same way that some researchers use their own way of measuring creativity, others only partially measure personality (sometimes measuring types and not traits, or a single trait). This treatment of personal factors limits the possibilities of aggregating data in meta-analysis. The field could be improved by using standardized personality questionnaires and reporting all data points necessary.\n\nSeveral studies measured the relationship between individual factors and group creativity, but as they did not report information essential for a meta-analysis, we could not include them. Of the 11 studies included, we requested the information for 6 of them. 8 additional studies could not be included because we were unable to contact the authors. Thus, we could have nearly doubled the number of studies included if information had been made available. The field of the research could be improved by systematically sharing the raw data and the analysis conducted. In addition to the benefit of the aggregation into a meta-analysis, this would allow for the conduct of individual participant data (IPD) meta-analyses (van Aert, 2022).\n\nA traditional meta-analysis is conducted at the group level - in other words, by asking the question “How do average group personal factors correlate with average group creativity?” An IPD meta-analysis can answer a more precise question: “How does an individual’s personality trait in this group correlate with his or her creativity in the group?” This question cannot be answered without data at the individual level.\n\nThe power of the studies was very low, around 13.5%. The number of participants is quite high (see Table 2), but the correlations seem to be extremely low, which requires an extremely high number of participants to indicate an effect if it exists. Again, reporting the raw data at the individual level would increase the precision of the estimates, improving the power of the study without the need to dramatically increase the number of participants.\n\nThe studies included were conducted in the USA, UK, China, Germany, Singapore, the Netherlands, and Romania. More importantly, many of the studies were performed on students doing group projects. It would be preferable to conduct studies in other contexts, including non-WEIRD, non-student samples. The many moderators that we tried to highlight were not investigated enough or were not investigated at all. We recommend that researchers methodically record all the data relating to the context of the creative activity, in particular the time allocated to participants, the type of task, the number of participants per group, and the individual characteristics of the participants (demographics, type of recruitment, randomization of the participants in groups or not, etc.).\n\nOne should be cautious in drawing a relationship between perceived creativity and actual creativity. For example, Pretz and McCollum (2014) did not find evidence for a relationship between self-rated and expert-rated creativity (r = -.07). Professionals wishing to improve group creativity should use objective measures of creativity, or expert observations, rather than relying on personal or peer measures. This could be done through a common definition of originality and usefulness, followed by a pre-test rating by peers. To this objective, it is possible to define an intra-class correlation threshold for which the correlation is high enough to indicate that observers are homogeneously rating the originality and usefulness of ideas (typical thresholds are between 0.75 and 0.90, Koo & Li, 2016). Intraclass correlation is a type of correlation performed on groups of data, unlike Pearson correlation which operates on pairs of data (it is also called interclass correlation); however, the formulas used for both types of correlation are similar.\n\nIf the intra-class correlation is sufficient, then observers can continue to evaluate ideas. If the correlation is not sufficient, then it is necessary to find the cause of this lack of relationship, which may be related to a misunderstanding of the objective, difficulty in understanding the originality or usefulness of the ideas in relation to the creativity theme, or a difference in the appreciation of the ideas. After the exchange, the experts will carry out the analysis on a new sample until the intra-class correlation is sufficient to score all the ideas.\n\nIt seems important to increase the attention of researchers and professionals to individual differences in group creativity. Although it is difficult to make recommendations based on the meta-analysis results, the hypotheses stated remain possible. Fostering openness to new ideas, paying attention to factors promoting group dynamics (extraversion, agreeableness, low neuroticism, high emotional intelligence, low social anxiety, and low need for closure), and making sense of the common goal (motivation, need for cognition) remain possible avenues for improving creative outcomes in groups.\n\nIn particular, a conclusion can be made about creative self-efficacy. Self-efficacy was the only factor to show a positive relationship with group creative outcomes in the meta-analysis. One limitation of this relationship is that creative self-efficacy is not easy to develop. Several recent studies have failed to improve it (Capron Puozzo & Audrin, 2021; Ohly et al., 2017). However, these studies had extremely small sample sizes (n = 69 and n = 23 respectively).\n\nIt is also possible that there are several types of creative self-efficacy. Hughes et al. (2018) suggested that there are creative leaders and individuals who are more focused on a creativity support function. This leader/supporter distinction could be related to personality traits, but their relationship remains to be investigated.\n\nThe final finding concerns the environment associated with creativity. In this meta-analysis, only one moderating effect appears to be different from chance, namely time. This is a moderator that has been the subject of many studies on individual and team creativity. In particular, almost a third of the best ideas in terms of originality are generated in the first 5 minutes, and after 15 minutes, less than 10% of the ideas are of very good quality, while 50% of them are judged as bad (Reinig & Briggs, 2008). It is possible that personal factors that promote persistence on task (e.g., motivation, conscientiousness, sense of self-efficacy) also promote the possibility of having original ideas longer, a hypothesis that remains to be tested. Furthermore, in terms of the relationship between constructs, one study (Jung et al., 2015) indicated that people who generate the most ideas also come up with better quality ideas, with quality defined as an average between originality and usefulness. Another application of this type of study for professionals is to build on the most creative individuals to improve the overall creativity of all participants, regardless of their personal factors.\n\n\nConclusion\n\nThis meta-analysis was an attempt to understand the relationship between individual factors and group creativity. It shows a link between self-efficacy and indicators of group creativity with a low level of evidence, and a small and positive moderation effect of time. During the search phase, we found that most studies concern individual creativity, and studies concerning group creativity do not directly measure creativity, but the perception of creativity by an internal or observing member of the group. Direct measures of creativity (number of ideas generated, originality, and usefulness) appear to be anecdotal, and the results found seem to mostly indicate a lack of relationship. Self-efficacy, a well-known individual factor in improving performance and learning (Bandura, 1997), is positively associated with all of the group creative outcome measures. In other words, it appears that groups feeling they have the capacity to be creative are indeed creative, whether in terms of the number, originality, or usefulness of the ideas generated by these groups.\n\n\nAuthorship declaration\n\nPlease see the table below.\n\nContributor roles taxonomy.\n\n",
"appendix": "Data availability\n\nThe underlying data can be found in Bonnardel et al. (2023). The data are shared under the license CC-BY 4.0.\n\nThe project contains the following underlying data:\n\n• The meta-analytical dataset (data and code > creativitymeta.xlsx)\n\n• Literature search folder (bibliographic data)\n\nThe project contains the following underlying data:\n\n• Supplementary.pdf (pre-registration information and additional information about decisions, and deviations from Stage 1)\n\n• The analysis script (data and code > ma-brainstorm-analysis. Rmd and moderator analysis. Rmd)\n\n• The result outputs and figures from the analysis script in the result folder.\n\n• The track-changed version of the second stage manuscript in the PCI-RR stage 2: tracked changes version.\n\n• The stage 1 files in the Stage 1 folder (data and code with randomized results, Main manuscript.pdf, output of the code, and a supplementary.pdf )\n\n• The Main manuscript.pdf as accepted in Stage 2 by PCI.RR\n\n\nAcknowledgments\n\nWe thank Paul Paulus for conceptual input on the introduction and Brenton Wiernik for help with the statistical analysis.\n\n\nReferences\n\nAmabile TM: Creativity and Innovation in Organizations. Harvard Business School Background Note. 1996; pp. 239–396.\n\nAnderson LR, Fiedler FE: The effect of participatory and supervisory leadership on group creativity. J. Appl. Psychol. 1964; 48(4): 227–236. Publisher Full Text\n\nAnderson C, Spataro SE, Flynn FJ: Personality and organizational culture as determinants of influence. J. Appl. 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Publisher Full Text\n\nMoreau D, Gamble B: Conducting a Meta-Analysis in the Age of Open Science: Tools, Tips, and Practical Recommendations [Preprint]. PsyArXiv. 2020. Publisher Full Text\n\nMoreland RL, Levine JM, Wingert ML: Creating the ideal group: Composition effects at work.Witte EH, Davis JH, editors. Understanding group behavior, Small group processes and interpersonal relations. Lawrence Erlbaum Associates; 1996; pp. 11–35.\n\nMorgan SC: Facilitating idea generation in a team context: The effects of technique, perceived organizational support, individual differences, and satisfaction with idea generation (Order No. 9624214). ProQuest Dissertations & Theses Global. (304321581).1996. Reference Source\n\nMotyl M, Demos AP, Carsel TS, et al.: The state of social and personality science: Rotten to the core, not so bad, getting better, or getting worse? J. Pers. Soc. Psychol. 2017; 113(1): 34–58. Publisher Full Text\n\nMoynihan LM, Peterson RS: The Role of Personality in Group Processes.Personality and organizations.Schneider B, Smith DB, editors. Lawrence Erlbaum Associates Publishers; 2004; pp. 317–345.\n\nMutlu MD: The role of personality composition on team creativity and innovation. PhD thesis, University of Sheffield. 2017. Reference Source\n\nMumford MD, Todd EM, Higgs C, et al.: What is needed to think creatively at work? Knowledge and skills. Creativity and Innovation in Organizations; 2019; 41. . Publisher Full Text\n\nNijstad BA, De Dreu CKW: Creativity and Group Innovation: Creativity and Innovation Implementation. Appl. Psychol. 2002; 51(3): 400–406. Publisher Full Text\n\nNijstad BA, Stroebe W: How the Group Affects the Mind: A Cognitive Model of Idea Generation in Groups. Personal. Soc. Psychol. Rev. 2006; 10(3): 186–213. PubMed Abstract | Publisher Full Text\n\nNiu W, Liu D: Enhancing creativity: A comparison between effects of an indicative instruction « to be creative » and a more elaborate heuristic instruction on Chinese student creativity. Psychol. Aesthet. Creat. Arts. 2009; 3(2): 93–98. Publisher Full Text\n\nOhly S, Plückthun L, Kissel D: Developing Students’ Creative Self-Efficacy Based on Design-Thinking: Evaluation of an Elective University Course. Psychol. Learn. Teach. 2017; 16(1): 125–132. Publisher Full Text\n\nOrengo Castellá V, Zornoza Abad AM, Prieto Alonso F, et al.: The influence of familiarity among group members, group atmosphere and assertiveness on uninhibited behavior through three different communication media. Comput. Hum. Behav. 2000; 16(2): 141–159. Publisher Full Text\n\nOsborn AF: Applied imagination: Principles and procedures of creative problem-solving. Charles Scribner’s Sons; 1963.\n\nPage MJ, McKenzie JE, Bossuyt PM, et al.: Mapping of reporting guidance for systematic reviews and meta-analyses generated a comprehensive item bank for future reporting guidelines. J. Clin. Epidemiol. 2020; 118: 60–68. PubMed Abstract | Publisher Full Text\n\nPaterson TA, Harms PD, Steel P, et al.: An Assessment of the Magnitude of Effect Sizes: Evidence From 30 Years of Meta-Analysis in Management. J. Leadersh. Org. Stud. 2016; 23(1): 66–81. Publisher Full Text\n\nPaulus PB, Kenworthy JB: Overview of team creativity and innovation.Reiter-Palmon R, editor. Team creativity and innovation. Oxford University Press; 2018; pp. 11–38. Publisher Full Text\n\nPaulus PB, Nijstad BA: Group Creativity. Oxford University Press; 2003. Publisher Full Text\n\nPaulus PB, van der Zee KI : Creative processes in culturally diverse teams.Otten S, van der Zee KI , Brewer M, editors. Towards inclusive organizations: Determinants of successful diversity management at work. Psychology Press; 2015; pp. 108–131.\n\nPeeters MAG, Rutte CG, van Tuijl HFJM , et al.: Designing in Teams: Does Personality Matter? Small Group Res. 2008; 39(4): 438–467. Publisher Full Text\n\nPeter L, Michinov N, Besançon M, et al.: Revisiting the Effects of Gender Diversity in Small Groups on Divergent Thinking: A Large-Scale Study Using Synchronous Electronic Brainstorming. Front. Psychol. 2021; 12. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPretz JE, McCollum VA: Self-perceptions of creativity do not always reflect actual creative performance. Psychol. Aesthet. Creat. Arts. 2014; 8: 227–236. Publisher Full Text\n\nPuryear JS, Kettler T, Rinn AN: Relationships of personality to differential conceptions of creativity: A systematic review. Psychol. Aesthet. Creat. Arts. 2017; 11(1): 59–68. Publisher Full Text\n\nPutman VL, Paulus PB: Brainstorming, Brainstorming Rules and Decision Making. J. Creat. Behav. 2009; 43(1): 29–40. Publisher Full Text\n\nReinig BA, Briggs RO: On The Relationship Between Idea-Quantity and Idea-Quality During Ideation. Group Decis. Negot. 2008; 17(5): 403–420. Publisher Full Text\n\nReiter-Palmon R, Kaufman JC: Creative styles in the workplace: New vs different. Individual creativity in the workplace. Elsevier Academic Press; 2018; pp. 191–202. Publisher Full Text\n\nReiter-Palmon R, Wigert B, de Vreede T : Team Creativity and Innovation. Handbook of Organizational Creativity. Elsevier; 2012; pp. 295–326. Publisher Full Text\n\nRichter AW, Hirst G, van Knippenberg D , et al.: Creative self-efficacy and individual creativity in team contexts: Cross-level interactions with team informational resources. J. Appl. Psychol. 2012; 97(6): 1282–1290. PubMed Abstract | Publisher Full Text\n\nRoberts BW, Jackson JJ, Fayard JV, et al.: Chapter 25. Conscientiousness.Leary IMR, Hoyle RH, editors. Handbook of individual differences in social behavior. Guilford Press; 2009; pp. 257–273.\n\nSchäfer T, Schwarz MA: The Meaningfulness of Effect Sizes in Psychological Research: Differences Between Sub-Disciplines and the Impact of Potential Biases. Front. Psychol. 2019; 10: 813. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchilpzand MC, Herold DM, Shalley CE: Members’ Openness to Experience and Teams’ Creative Performance. Small Group Res. 2011; 42(1): 55–76. Publisher Full Text\n\nSchmitt MT, Branscombe NR, Postmes T, et al.: The consequences of perceived discrimination for psychological well-being: A meta-analytic review. Psychol. Bull. 2014; 140(4): 921–948. PubMed Abstract | Publisher Full Text\n\nSchmidt FL, Hunter JE: Methods of Meta-Analysis: Correcting Error and Bias in Research Findings. SAGE Publications, Ltd.; 2015. 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Psychol. 2022; 230(1): 60–72. Publisher Full Text\n\nvan Aert RCM , Wicherts JM, van Assen MALM : Conducting Meta-Analyses Based on p Values: Reservations and Recommendations for Applying p -Uniform and p -Curve. Perspect. Psychol. Sci. 2016; 11(5): 713–729. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVanGundy AB: Brain writing for new product ideas: an alternative to brainstorming. J. Consum. Mark. 1984; 1(2): 67–74. Publisher Full Text\n\nVan Kleeck A, Schwarz AL, Fey M, et al.: Should We Use Telegraphic or Grammatical Input in the Early Stages of Language Development With Children Who Have Language Impairments? A Meta-Analysis of the Research and Expert Opinion. Am. J. Speech Lang. Pathol. 2010; 19(1): 3–21. Publisher Full Text\n\nVosgerau J, Simonsohn U, Nelson LD, et al.: 99% impossible: A valid, or falsifiable, internal meta-analysis. J. Exp. Psychol. Gen. 2019; 148(9): 1628–1639. 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Publisher Full Text\n\nYao X, Li R: Big five personality traits as predictors of employee creativity in probation and formal employment periods. Personal. Individ. Differ. 2021; 182: 109914. Publisher Full Text\n\nZhang AY, Tsui AS, Wang DX: Leadership behaviors and group creativity in Chinese organizations: The role of group processes. Leadersh. Q. 2011; 22(5): 851–862. Publisher Full Text\n\nZhou J, George JM: When Job Dissatisfaction Leads to Creativity: Encouraging the Expression of Voice. Acad. Manag. J. 2001; 44(4): 682–696. Publisher Full Text"
}
|
[
{
"id": "312033",
"date": "07 Aug 2024",
"name": "Julia Rohrer",
"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\nWhat determines whether groups of people can come up with ideas that are both original and useful? Since the 1960s, this question has been intensively studied with the help of more or less structured group creativity activities such as brainstorming or creative problem solving, with subsequent rating of the generated ideas.\nIn this line of research, personal factors—such as personality traits, and other interindividual differences in emotion and cognition—have received substantial attention as potential correlates of creative outcomes of group activities. This has spawned a sprawling literature that, to date, has not yet been synthesized. Thus, empirical findings in this literature, which are also sometimes contradictory, have not yet been well-integrated.\nIn the present study, Fillon et al. conducted the first meta-analysis of correlations between personal factors and group creativity outcomes. The authors searched and synthesized the existing published literature according to predetermined criteria to (1) assess the overall relationship between a broad list of personal factors and creativity outcomes in group settings and (2) explore potential moderators of these relationships.\n\nIn total, 11 studies could be included in the meta-analysis. They provided weak support for a positive correlation between self-efficacy and the three investigated group creative outcomes, number of ideas, originality of ideas, and usefulness of ideas. With respect to moderators, many of the planned analyses could not be conducted due to the low number of studies. The only finding that arose was weak evidence for the idea that time constraint moderates associations: relationships between personal factors and group creativity outcomes were slightly stronger for tasks limited to 20 minutes rather than 10 minutes. Statistical power overall was low across studies. The authors conclude their meta-analysis with the observation that the available data on the topic are very limited. They suggest that to improve our knowledge of the topic, future studies should adhere to standardized creativity methods and protocols and implement expert ratings of creativity. They also call for increasing the availability of raw data in this field of study to improve the accumulation of knowledge about links between personal factors and the creative performance of groups.\nThe Stage 2 manuscript was evaluated over one round of in-depth review provided by the recommender and Chris Chambers, as the original reviewers were no longer available. Based on additional changes to the manuscript, the recommender judged that the manuscript met the Stage 2 criteria and awarded a positive recommendation.\n\nURL to the preregistered Stage 1 protocol: https://osf.io/nybg6\n\nLevel of bias control achieved: Level 3. At least some data/evidence that was used to answer the research question had been previously accessed by the authors (e.g. downloaded or otherwise received), but the authors certified that had not yet observed ANY part of the data/evidence prior to IPA.\n\nAre the data able to test the authors’ proposed hypotheses by satisfying the approved outcome-neutral conditions (such as quality checks, positive controls)? Yes\n\nAre the introduction, rationale and stated hypotheses the same as the approved Stage 1 submission? Yes\n\nDid the authors adhere precisely to the registered experimental procedures? If not, has an explanation been provided regarding any change? Yes\n\nAre any unregistered post hoc analyses added by the authors justified, methodologically sound and informative? Yes\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/13-904
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https://f1000research.com/articles/9-241/v1
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07 Apr 20
|
{
"type": "Brief Report",
"title": "Placenta previa as a risk factor for antenatal- and peripartum periventricular leukomalacia resulting in cerebral palsy in Japan: a retrospective study",
"authors": [
"Shunji Suzuki"
],
"abstract": "Intrapartum fetal heart rate monitoring abnormalities had been reported to correlate with decreased umbilical artery base excess associated with neonatal seizures. After encountering a child born at 35 weeks of gestation diagnosed with cerebral palsy associated with periventricular leukomalacia (PVL) without fetal heart rate monitoring abnormalities, a review and analysis of summary reports of PVL cases published on the home page of the Japan Obstetric Compensation System for Cerebral Palsy (JOCSC). Based on the case and the review of the reports of PVL cases from JOCSC, placenta previa may be a risk factor for antenatal- and peripartum PVL resulted in cerebral palsy in Japan.",
"keywords": [
"periventricular leukomalacia",
"placenta previa",
"Japan"
],
"content": "Introduction\n\nBrain injury in premature infants is generally thought to primarily consist of periventricular leukomalacia (PVL), a distinctive form of cerebral white matter injury. PVL occurs most commonly in premature infants born at less than 32 weeks' gestation. In an earlier study in Japan, frequent moderate variable deceleration on fetal cardiotocogram (CTG) was observed to be a cause of antenatal PVL in premature infants1. In the report by Ito et al.1, frequent moderate variable decelerations on fetal CTG were observed frequently for infants with antenatal PVL (80.0%) than control infants (27.3%, p < 0.05). In addition, in low birth weight infants, intrapartum severe variable deceleration or prolonged deceleration have been suggested to play a causal role in PVL2. Although intrapartum fetal heart rate monitoring abnormalities had been reported to correlate with decreased umbilical artery base excess associated with neonatal seizures, recently it has been observed to have no relation to perinatal mortality or pediatric neurologic morbidity3,4. The main factor related to the presence of PVL has been suggested to be gestational age4.\n\nWe encountered a case of PVL without fetal heart rate monitoring abnormalities. Subsequently, a review and analysis of the summary reports of PVL cases published on the home page (HP) of the Japan Obstetric Compensation System for Cerebral Palsy (JOCSC) was conducted. We conclude that placenta previa may be a risk factor for antenatal- and peripartum PVL resulting in cerebral palsy (CP) in Japan.\n\n\nCase report\n\nAn elective cesarean section was performed at 35 weeks’ gestation because of placenta previa in the mother with warning bleeding of 60 g. A 2346-g, male infant was delivered with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. The mother’s pregnancy had progressed uneventfully until the day before the cesarean section. The preoperative fetal CTG, performed 20 minutes before the cesarean section, showed a reassuring fetal status without any fetal heart rate decelerations. The umbilical artery pH was 7.334. The total blood loss during cesarean section was 1,080 g. The infant had no problems during his neonatal period; however, he was diagnosed with CP associated with PVL at the age of 2.\n\n\nReview and analysis of PVL cases on JOCSC\n\nTo re-examine previous findings in Japan regarding PVL cases, we reviewed the summary reports of antenatal- and peripartum PVL cases published on the HP of the JOCSC launched in 20095. This is a free to access resource, and the cause analysis reports (summary reports) of the patients can be accessed here: http://www.sanka-hp.jcqhc.or.jp/documents/analysis/index.html. Those eligible for inclusion in the compensation scheme are infants born between 2009 and 2014 with a birth weight of ≥ 2,000 g, gestation of ≥ 33 weeks and infants born between 2015 and 2019 with a birth weight of ≥ 1,400 g, gestation of ≥ 32 weeks, and severe disability due to CP independent of congenital causes or factors during the neonatal period or later. In the current study, we searched all summary reports published by the end of March 2020 using the keyword 'PVL'. We have excluded the cases of PVL identified as neonatal cause, such as late circulatory collapse, birth injury, and multiple pregnancies, from the analysis. The following variables were extracted from the reports:fetal heart rate decelerations, intrauterine infection, placental abruption and placenta previa.\n\nData are presented as number (%). SPSS Statistics software version 20 (IBM Csorp., Armonk, NY, USA) was used for statistical analyses. For statistical analysis, the Χ2 test was used for the categorical variables between cases with and without fetal heart rate decelerations. Differences with p < 0.05 were considered significant.\n\n\nFindings\n\nThere were 209 cases of PVL published in the HP of JOCSC retrieved in January 2020. We examined the presence or absence of moderate/severe decelerations (MSDs) on fetal CTG in 187 cases. Cases excluded were 13 cases of monochorionic twins and 9 cases of postnatal PVL due to late circulatory collapse (n = 6), neonatal hypoglycemia (n = 2) and neonatal hyperkalemia (n = 1). Table 1 shows the clinical characteristics of the 187 cases of antenatal- and peripartum PVL with and without MSDs on fetal CTG. The incidence of neonatal asphyxia in the cases with MSDs was higher than in those without MSDs (p < 0.01); however, the percentage of cases without MSDs was higher than those with MSDs (73.3 vs. 26.7%, p < 0.01). In cases without MSDs, the percentage of neonates born at term was higher than those with MSDs (p = 0.04). These cases might have potentially transient episodes leading to PVL in the uterus between 26 and 32 weeks of gestation. Our case may be same as these cases.\n\nTable 2 shows the perinatal complications in the cases of antenatal- and peripartum PVL with and without MSDs on fetal CTG. The incidence of intrauterine infection and placental abruption in the cases with MSDs was higher than those without MSDs (p < 0.01), while the incidence of placenta previa in the cases without MSDs was higher than those with MSDs (p = 0.04). The former results were as expected, while the latter may be a new finding. The percentage of placenta previa in the cases of PVL was 5.7% (12/209), which seemed to be higher than the total percentage of placenta previa reported in Japan (0.3-0.5%)6.\n\n\nDiscussion\n\nTo date, some possible mechanisms leading to PVL in cases of placenta previa has been discussed in Japan7,8. Oda et al.7 reported that the main risk factor for PVL in preterm placenta previa is an initial antepartum hemorrhage <28 weeks of gestation and they speculated that decreased placental perfusion in the second trimester of pregnancy is associated with the developmental window of vulnerability for PVL. However, Furuta et al.8 observed that acute and massive bleeding from placenta previa at around 30 weeks of gestation is a risk factor for PVL and CP requiring careful neonatal follow-up. However, in the 12 cases of placenta previa in that study, massive bleeding and initial bleeding < 28 weeks of gestation were observed in only 4 (33.3%) and 1 cases (8.3%) Kmazaki et al.9 observed that gross lesions with disturbance of uteroplacental circulation including massive retroplacental hematoma, extensive infarction or thrombosis, and marked basal or perivillous fibrin deposition frequently in placentae in cases of antenatal- and peripartum PVL. They also observed the high frequency of ischemic changes in villi in those placentae. The same findings have been reported to be observed in cases of placenta previa10. The same findings may have occurred in our case.\n\nBased on the data from JOCSC, serious abnormal fetal heart rate patterns were not observed in approximately 70% of cases with antenatal- and peripartum PVL on fetal CTG, and placenta previa itself may be associated with the development of antenatal- and/or peripartum PVL.\n\n\nData availability\n\nThe Japan Obstetric Compensation System for Cerebral Palsy (JOCSC) for is a free to access resource. Cause analysis reports (summary reports) for patients with periventricular leukomalacia can be accessed here: http://www.sanka-hp.jcqhc.or.jp/documents/analysis/index.html, Feb 12, 2020). These reports are in Japanese.\n\nFigshare: Data of PVL in Japan, https://doi.org/10.6084/m9.figshare.12033501.v311.\n\nThis project contains the following underlying data:\n\nDataset 1. Raw data for gestational age, delivery mode, birth weight, Apgar scores, FHR deceleration, placenta abruption, complications, placenta previa from 187 the cases of periventricular leukomalacia on the home page of the Japan Obstetric Compensation System for Cerebral Palsy (JOCSC: http://www.sanka-hp.jcqhc.or.jp/documents/analysis/index.html, Feb 12, 2020).\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\nConsent\n\nWritten informed consent for publication of the clinical details of the case report was obtained from the mother in the case report.",
"appendix": "References\n\nIto T, Kadowaki K, Takahashi H, et al.: Clinical features of and cardiotocographic findings for premature infants with antenatal periventricular leukomalacia. Early Hum Dev. 1997; 47(2): 195–201. PubMed Abstract | Publisher Full Text\n\nIbara S, Ikenoue T, Sameshima H, et al.: [The perinatal risk factors and periventricular leukomalacia (PVL) in premature infants--relationship between fetal heart rate decelerations and PVL]. No To Hattatsu. 1996; 28(2): 135–137. PubMed Abstract\n\nGraham EM, Petersen SM, Christo DK, et al.: Intrapartum electronic fetal heart rate monitoring and the prevention of perinatal brain injury. Obstet Gynecol. 2006; 108(3 Pt 1): 656–666. PubMed Abstract | Publisher Full Text\n\nRomero-Guzman GJ, Lopez-Munoz F: [Prevalence and risk factors for periventricular leukomalacia in preterm infants. A systematic review]. Rev Neurol. 2017; 65(2): 57–62. PubMed Abstract\n\nJapan Council for Quality Health Care: The Japan Obstetric Compensation System for Cerebral Palsy. 2020. Reference Source\n\nJapan Society for Obstetrics and Gynecology: Placenta previa (in Japanese). 2020. Reference Source\n\nOda N, Takeuchi K, Tanaka A, et al.: Obstetric risk factors associated with the development of periventricular leukomalacia in preterm infants born to mothers complicated by placenta previa. Fetal Diagn Ther. 2008; 24(4): 345–348. PubMed Abstract | Publisher Full Text\n\nFuruta K, Tokunaga S, Furukawa S, et al.: Acute and massive bleeding from placenta previa and infants' brain damage. Early Hum Dev. 2014; 90(9): 455–458. PubMed Abstract | Publisher Full Text\n\nKumazaki K, Nakayama M, Sumida Y, et al.: Placental features in preterm infants with periventricular leukomalacia. Pediatrics. 2002; 109(4): 650–655. PubMed Abstract | Publisher Full Text\n\nBiswas R, Sawhney H, Dass R, et al.: Histopathological study of placental bed biopsy in placenta previa. Acta Obstet Gynecol Scand. 1999; 78(3): 173–179. PubMed Abstract | Publisher Full Text\n\nSuzuki, Shunji: Data of PVL in Japan.figshare. Dataset. 2020. http://doi.org/10.6084/m9.figshare.12033501.v3"
}
|
[
{
"id": "62089",
"date": "27 Apr 2020",
"name": "Ambrogio Pietro Londero",
"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 read the article by Suzuki S entitled: \"Placenta previa as a risk factor for antenatal- and peripartum periventricular leukomalacia resulting in cerebral palsy in Japan: a retrospective study\" with interest.\nThe argument is very interesting but I have some points to highlight in order to improve the manuscript itself:\nMajor issues:\nThe abstract does not reflect in a proper manner the content of the manuscript. In particular, the conclusion in the abstract is a clear overstatement. In fact, the data analyzed in the manuscript do not allow any kind of conclusion about a correlation between placenta previa and neonatal periventricular leukomalacia. In the dataset, only cases of neonatal periventricular leukomalacia without controls are present.\n\nFor the same reason, the title of the article is also not appropriate, and also the manuscript's main-text itself should be fixed.\n\nFor the clinical case report, I suggest following the CARE guidelines.\n\nMinor issues:\nA minor issue is that the clarity of the whole manuscript would benefit from a revision of the English language.\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? 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? No",
"responses": [
{
"c_id": "5455",
"date": "04 May 2020",
"name": "Shunji Suzuki",
"role": "Author Response",
"response": "Thank you very much for the comments and critique of my manuscript. I have been able to respond positively to each suggestion and we believe the paper has been strengthened. The changes are highlighted with red color. I have re-written the abstract, case report and the title according to your suggestions. In addition, my English has been edited. Thank you very much for your suggestions, again. I do hope and trust that with these changes the manuscript is now acceptable for publication. Thank you for considering my paper.Sincerely yours,Shunji Suzuki, MDDepartment of Obstetrics and Gynecology,Japanese Red Cross Katsushika Maternity Hospital5-11-12-2 Tateishi, Katsushika-ku, Tokyo 124-0012 JapanTel: +81-3-3693-5211Fax: +81-3-3694-8725e-mail: czg83542@mopera.ne.jp"
},
{
"c_id": "8958",
"date": "04 Nov 2022",
"name": "Shunji Suzuki",
"role": "Author Response",
"response": "Dear Professor Ambrogio Pietro Londero、 Thank you very much for your previous suggestions. I have responded to your questions on May 2020. If you have further suggestions. Please guide me, again. Sincerely, Shunji Suzuki"
}
]
}
] | 1
|
https://f1000research.com/articles/9-241
|
https://f1000research.com/articles/13-899/v1
|
06 Aug 24
|
{
"type": "Software Tool Article",
"title": "MirtronStructDB: A Comprehensive Database of Mirtrons with Predicted Secondary Structures",
"authors": [
"Shumin Li",
"Franklin Wang-Ngai Chow",
"Lei Chen",
"Junhao Su",
"Syed Shakeel Ahmed",
"Ruibang Luo",
"Franklin Wang-Ngai Chow",
"Lei Chen",
"Junhao Su",
"Syed Shakeel Ahmed"
],
"abstract": "Motivation Mirtrons, a vital category of non-canonical microRNAs (miRNAs) originating from exon-intron boundaries through splicing mechanisms, play crucial roles in cellular processes. However, existing databases lack the latest data and structural information, hindering understandings of mirtron formation and functions.\n\nResults We introduce MirtronStructDB, an online database addressing these gaps by incorporating over 350 novel mirtrons. Significantly, it provides corresponding predicted RNA secondary structures, offering a deeper understanding of the functional roles and mechanisms of all mirtrons. This enhances previous repositories, offering a total of 4,209 mirtron records spanning 25 species from 46 publications. Our database contributes for unraveling patterns and functions in mirtrons across species and diverse structural features. MirtronStructDB allows users to freely browse, search, visualize, and download data via a user-friendly interface.\n\nAvailability MirtronStructDB is accessible at: http://www.bio8.cs.hku.hk/msdb/.\n\nContact\nlishumin@connect.hku.hk, rbluo@cs.hku.hk",
"keywords": [
"Mirtron",
"Secondary Structure"
],
"content": "Introduction\n\nMirtrons are a vital category of non-canonical microRNAs (miRNAs). MicroRNAs represent a crucial class of small RNAs that play significant roles in various post-transcriptional cellular processes.1 Conventionally, miRNAs are processed from longer primary transcripts, known as pri-miRNAs, via sequential enzymatic cleavage steps involving the Drosha or Dicer proteins. However, a distinct class of miRNAs, termed mirtrons, have been identified that they follow an alternative processing pathway. Mirtrons originate from exon-intron boundaries through splicing and are independent of Drosha or Dicer cleavage. The initial detection of mirtrons occurred in D. melanogaster and C. elegans2 and subsequent studies confirmed their presence in mammals,3 plants,4 and viruses.5 Notably, mirtrons have demonstrated involvement in diverse biological processes, including cell development and cancer.6 To facilitate the exploration of mirtrons, an organized database, MirtronDB, was launched in 2019, collecting 3,833 precursors or mature mirtrons across 18 species.7 However, MirtronDB is limited by the absence of the latest data and, more significantly, structural information—a critical factor in miRNA maturation and distinguishing canonical and non-canonical miRNAs.8\n\nTo address these limitations, we present MirtronStructDB, an updated database that offers corresponding secondary structures of all mirtrons, along with an addition of over 350 novel mirtrons that are currently unavailable in existing databases. Furthermore, our user-friendly web interface provides browsing, searching, visualization, and downloading of all stored data. Through timely updates and comprehensive structural information, MirtronStructDB aims to contribute to the advancement of mirtron research and facilitate investigations into their functional roles and mechanisms. MirtronStructDB is publicly accessible at: http://www.bio8.cs.hku.hk/msdb/.\n\n\nMethods\n\nData collection and processing\n\nMirtronStructDB was constructed through a two-fold data collection strategy (Figure 1A). Initially, we obtained the data from mirtronDB7 by downloading their available information as a primary source. Subsequently, we conducted a comprehensive literature search using the term ‘mirtron OR mirtrons’ from PubMed to collect additional publications related to mirtron discoveries. All the collected data underwent a standardization process and was integrated into MirtronStructDB. In cases where certain fields were missing from the original papers, temporarily placeholders (‘tbu’ indicating ‘to be updated’) were employed. To augment the database and investigate the functions and mechanisms of diverse mirtrons, we predicted the RNA secondary structures for all the collected data with sequence information. This prediction was performed through the RNAstructure Web Server with default parameters.9\n\nA) Workflow of data collection and preprocessing. B) Main modules of MirtronStructDB: search and filter, browse by species, demonstration and download.\n\nIn summary, MirtronStructDB offers a comprehensive dataset comprising 1,569 precursors and 2,640 mature mirtrons spanning 25 species, sourced from 46 publications. Of these, 163 precursors and 223 mature mirtrons were first documented in a dedicated mirtron database. And 9 species were first collected and reported in MirtronStructDB. In addition, a total of 12,555 RNA secondary structures were predicted for better understandings of the functional roles and mechanisms of mirtrons. Detailed information was provided in Data availability statement.\n\nWeb application implementation\n\nThe online web server was developed with the Flask web framework (v1.1.4) (https://github.com/pallets/flask) as the backend. It is deployed on an Ubuntu Linux server equipped with 48 Intel Xeon CPUs and 189GB of memory. All data is stored in a SQLite database, managed by the SQLAlchemy toolkit (v2.5.1) (https://www.sqlalchemy.org/).\n\nThe frontend of MirtronStructDB with a user-friendly design, crafted using Bootstrap (v3) (https://getbootstrap.com/) and adminLTE (v2.4.18) (https://github.com/ColorlibHQ/AdminLTE), and dynamically generated through the JINJA2 templating engine (v2.11.3) (https://jinja.palletsprojects.com/en/3.1.x/templates/). The web service is hosted by Apache2 and Gunicore modules, guaranteeing high performance and stability.\n\nMirtronStructDB is available to the community through its web-based interface and is freely available. It can also be run locally with a typically 2GB RAM and a dual-core CPU. It is compatible with popular web browsers, including Microsoft Edge, Google Chrome, Firefox and Safari.\n\nThe web portal has three primary modules: search and filter, browse by species, and demonstration and download. The overview is shown in Figure 1B. Users can either start with search and filter or browse by species to get the mirtron list and then select individual mirtrons to view their details. Usages listed below:\n\nSearch and filter: To facilitate the use of MirtronStructDB, a search and filter can be performed through clicking the ‘Search’ button from the top navigation bar. Users can type the IDs of mirBase, host gene symbols, DOIs or keywords of papers in the search box to retrieve all relevant mirtrons. Additionally, users can apply filters based on preferred species and sources to customize their search results.\n\nBrowse by species: We also provide a gallery page which categorizing mirtrons by species. Users can access it through clicking ‘Browse’ button of the navigation bar. Mirtron summaries for each species are presented, and users can explore detailed information by clicking on individual species.\n\nDemonstration and download: Individual mirtrons can be accessed through the mirtron detail page. Two sections were shown: The first section includes basic information including the species, corresponding precursors or mature mirtrons, sequences, strand, chromosome position, source papers, etc. The second section displays predicted secondary structures. Users are flexible to explore and download data based on their own needs.\n\n\nDiscussion\n\nMirtronStructDB is a comprehensive database with an extensive collection of over 350 novel mirtrons accompanied by their predicted secondary structures. This database not only presents an updated catalog of mirtrons across diverse species but also provide structural insights into the entire spectrum of mirtrons. MirtronStructDB make it feasible for experimental biologists seeking identification of relevant mirtrons for distinct species, sources, or specific research requirements. Furthermore, MirtronStructDB offers computational biologists an opportunity to delve into its rich information, particularly the sequence contexts and structural features it provides. With the accumulated data of mirtronStructDB, we anticipate the emergence of novel computational methods to expedite the prediction and identification of mirtrons across a broader spectrum of species. This advancement is expected to deepen our understanding of the unique formation mechanisms and functions of mirtrons.\n\n\nEthics and consent\n\nEthical approval and consent were not required.\n\n\nAuthor contributions\n\nR. L. And S. L. conceived the study. S. L. designed the web interface and the analyses. F. W. C., L. C., J. S., and S. S. A. evaluated the analysis results. All authored drafted and approved the manuscript.",
"appendix": "Data availability\n\nZenodo: Source data of Mirtronstructdb - A comprehensive database of mirtrons with predicted secondary structure. https://zenodo.org/doi/10.5281/zenodo.13118506. 10\n\nThe project contains the following underlying data:\n\n- msdb_data.csv (the mirtron collection table, including the following columns: Unique ID, mirtron name, type, species, hairpin arm, sequence, chromosome, start, end, strand, host gene, 3p-arm mature miRNAs, 5p-arm mature miRNAs, precursor name, data source, PMID, paper title, DOI, other information).\n\n- msdb_structures.tar.gz (the SVG images of the predicted secondary structures based on the mirtron sequences).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nBartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2): 281–297. Publisher Full Text\n\nRuby JG, Jan CH, Bartel DP: Intronic microRNA precursors that bypass Drosha processing. Nature. 2007; 448(7149): 83–86. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBerezikov E, Chung WJ, Willis J, et al.: Mammalian mirtron genes. Mol. Cell. 2007; 28(2): 328–336. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhu QH, Spriggs A, Matthew L, et al.: A diverse set of microRNAs and microRNA-like small RNAs in developing rice grains. Genome Res. 2008; 18(9): 1456–1465. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRasschaert P, Figueroa T, Dambrine G, et al.: Alternative splicing of a viral mirtron differentially affects the expression of other microRNAs from its cluster and of the host transcript. RNA Biol. 2016; 13(12): 1310–1322. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSalim U, Kumar A, Kulshreshtha R, et al.: Biogenesis, characterization, and functions of mirtrons. Wiley Interdiscip. Rev. RNA. 2022; 13(1): e1680. PubMed Abstract | Publisher Full Text\n\nDa Fonseca BHR, Domingues DS, Paschoal AR: mirtronDB: a mirtron knowledge base. Bioinformatics. 2019; 35(19): 3873–3874. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTitov II, Vorozheykin PS: Comparing miRNA structure of mirtrons and non-mirtrons. BMC Genomics. 2018; 19(3): 114. PubMed Abstract | Publisher Full Text | Free Full Text\n\nReuter JS, Mathews DH: RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinformatics. 2010; 11(1): 129. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi S, Chow F, Chen L, et al.: Source data of Mirtronstructdb - A comprehensive database of mirtrons with predicted secondary structure. Zenodo. 2024. Publisher Full Text\n\nLi S, Chow F, Chen L, et al.: Source code of Mirtronstructdb - A comprehensive database of mirtrons with predicted secondary structure. Zenodo. 2024. Publisher Full Text"
}
|
[
{
"id": "312748",
"date": "21 Aug 2024",
"name": "Panos Kakoulidis",
"expertise": [
"Reviewer Expertise Structural Bioinformatics",
"RNAi"
],
"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 created an up-to-date online database that hosts data about mirtrons. The dataset of the database is an extension of a previously published database. The user can browse the data by species. Alternatively, the user can search for a particular entry by entering keywords (Gene Symbol or miRBase ID) and filtering results by species or source publication. Each entry displays sequence information and includes figures of alternative RNA secondary structure predictions, deriving from the established RNAStructure package. The data are available for download in CSV format. The source code of the website is available on GitHub.\n\nI believe that this is a valuable resource which will aid the research of mirtrons. The website is user-friendly with a clean design and effectively guides the user to the sought information. The information can be exported to a user-friendly format with appropriate headers. This is a resource that I would personally use.\n\nMy concerns/suggestions are stated below:\n1) RNA structure data\na) I think that the text should include the rationale behind selecting RNAStructure for this task. Since RNA structure is a central aspect of this work (the database is named 'MirtronStructDB'), I would expect more details and insights to be provided about the procedure, its limitations and the data produced.\n\nb) It would be very helpful to include the CT outputs from RNAStructure in your database in addition to the figures. Ideally, a new field in the data could be dedicated to the predicted secondary structure in dot-bracket notation based on the CT outputs.\nc) During last years, there has been progress on RNA 3D structure prediction and I would suggest you to consider including 3D structures in your data. Mirtrons are short sequences without the intricacies of e.g. rRNA, therefore it should be feasible in terms of resources and accuracy to produce such structural 3D models.\n\n2) Web page\na) Input checking:\n\nWhen selecting species (e.g. Homo Sapiens) and source (Discovery of hundreds of mirtrons in mouse and human small RNA data) the system either returns an internal error message or zero results if the user has not entered anything in the search field. I would suggest either freezing the submission button or returning all results from the selected source (the latter might be more useful).\nb) Are there any tailed mirtrons in the data? It would be interesting to have a distinction between mirtron types if it is possible, such as conventional and tailed mirtrons\nc) Please consider adding a note in the UI explaining the 'to be updated' ('tbu') abbreviation in the data. Alternatively, you could just hide the abbreviation for less noise on what the user is seeing.\n\nd) I noticed that the hsa-mirtron-1230 entry of the examples is missing a MaxExpect figure. Also, the ptr-mir-1226 entry includes two Fold Structure figures, however the RNAStructure web server outputs a single one. Maybe you should double-check these cases, if this output shown is not the intended one.\n\nOverall, I believe this work will be helpful to the community and promote the research on this topic. The modern and simple design of the website offers increased accessibility to the presented information and with minimal polishing of the code, the usability will reach its intended maximum. However, I would expect from an RNA structure database to offer structural information in more data forms than the ones that are currently provided. I look forward to seeing updates on this work.\n\nIs the rationale for developing the new software tool clearly explained? Partly\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? Partly\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes",
"responses": []
},
{
"id": "312746",
"date": "19 Sep 2024",
"name": "Lachlan Coin",
"expertise": [
"Reviewer Expertise Bioinformatics",
"genomics and transcriptomics"
],
"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\nShunmin Li and co-authors have developed a database for Mirton structures, which looks like a useful resource for the community. Mirtons are an important subclass of micro-RNA and new resources for exploring their role in biology and medicine are valuable.\nThe database is at first glance, quite similar to http://mirtrondb.cp.utfpr.edu.br/index.php, which is where the authors have obtained the bulk of the data for MirtonstructDB.\n\nThe main novelty of MirtonStructDB is that it has calculated RNA secondary structure for Mirtons in the database, which are shown when the user looks at a specific Mirton page.\n\nAdditionally the authors point out the MirtonDB has not been updated for some years and they increase the number of species annotated, and identify new Mirtons via a literature search.\n\nThe authors say that MirtonStructDB will continue to be updated, but its not clear to me that this will not run into the same problem , and there is not a clear plan to ensure the database is up to date.\n\nI have some suggestions to improve this paper, and also the utility of the database\n1. Could the authors describe the quality control processes to ensure that Mirtons reported in the literature satisfy the criteria to be classified as Mirtons. What other quality control / verification processes are in place. 2. The authors describe a standardization process before integration into MirtonStructDB, could they describe this? 3. Have any de-duplication processes been carried out on the data 4. Could the authors provide the reference genome used for each of the species. 5. can the authors better describe the procedure to keep this database up-to-date 6. I felt that there were some important details about Mirtons which could have been explained better. For example, in the introduction, the authors mention canonical vs non-canonical .. what does this mean?\n\nAlso why is secondary structure important in this distinction.\n\nCan canonical vs non canonical be indicated in the record, as well as the evidence supporting this? 7.\n\nSince the main novelty of this database is the secondary structure, it would be good to be able to download this information across all entries in a machine readable form, in order to enable AI/ML applications (rather than just access the image through each entry). There are a number of formats for representing this, such as dot bracket notation, or washington university notation. 8. Can the authors provide some stats on the reliability of the entries they provide .e.g how many false positive entries are there\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? Partly\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-899
|
https://f1000research.com/articles/13-898/v1
|
06 Aug 24
|
{
"type": "Research Article",
"title": "Understanding of middle east women’s decisions and barriers to use family planning methods",
"authors": [
"Hawraa Hussein Ghafel"
],
"abstract": "Background when family planning methods not use, there is a higher chance of high fertility, which raises health risks for both mother and infant and lowers quality of life by limiting access to jobs employment, education, and nutrition. Unsatisfactory needs and poor family planning use can be explained by fear of negative impacts, rejection from couples, limits in knowledge, and social condemnation.\n\nObjectives To understanding the Middle East women’s barriers about make decisions and use of family planning methods\n\nMethodology A descriptive and analytic (cross sectional) study, conducted at six Arabic countries includes a non-probability (purposive sample) consist of (198) women. Which were selected according to inclusion criteria that are women in reproductive age, primiparous and multiparous mothers, and mothers who attended primary healthcare centers.\n\nResults Women are with average age of 32.23±7.9 years in which the highest percentage is seen with age group of 30-39 (40.4%). women have high affective barrier to avoid family planning methods (total grand mean= 2.60); have high behavioral barriers to avoid family planning methods (total grand mean= 2.56); and have high cognitive barriers to avoid family planning methods (total grand mean= 2.56). So, the mean scores indicate high among most of affective, behavioral, and cognitive barriers.\n\nConclusions There are many potential barriers which can negatively impact the Middle East women’s decision about their reproductive life (affective, behavioral and cognitive) barriers. Despite the fact that family planning faces several challenges in the Middle East, governments and civil society organizations are working to find solutions to improve access to family planning services, promote education, hold candid conversations about reproductive health with local communities. Empowering the role of nurse in family planning to educate the couples about contraceptive methods and how to help them to choice the appropriate method.",
"keywords": [
"Middle East",
"Women’s Decisions",
"barriers",
"Family planning methods"
],
"content": "Introduction\n\nFamily planning can hasten a nation’s efforts to end poverty and realize its developmental objectives. Universal access to family planning and other reproductive health treatments is recognized as one of the most important objectives of the Millennium Development Goals (MDGs) of the United Nations.1–3\n\nThe high fertility that results from not using family planning methods also raises the risks of health problems for the mother and infant, which lowers quality of life and limits access to jobs employment, education, and nutrition. Family planning methods can be very important for population dynamics, which aid in the nation’s economic stabilization and enable it get over the challenges posed by faster population growth. Unsatisfactory needs and poor family planning use can be explained by fear of negative impacts, rejection from couples, decrease knowledge, and social condemnation. Cultural variations have also been mentioned as having an impact on the use of family planning, particularly with regard to conventional expectations and aspirations for more children and lines. Access to safe abortion services and contraception methods is correlated with low incidence of unwanted pregnancy. After women choose which method.4The ability of women to make freely chosen decisions on family planning needs and options, or to disagree with their husbands or partners on these matters, is known as women’s decision-making power in family planning. Couples that use family planning (FP) try to limit the number of children they have. Women make decisions about family planning use based on a variety of factors, such as delaying marriage, having access to reliable information, having open discussions about family planning options and needs with partners, family members, and the community, and making their own decisions about controlling their fertility, including using family planning methods more frequently.5\n\nFamily planning lowers maternal mortality and morbidity and helps prevent unintended pregnancies. Compared to other nations in the Eastern Mediterranean Region, Iraq still has a comparatively low prevalence of contraception (58%), and the country’s overall fertility rate (4.2 children per woman) and unmet requirement percentages (12%) are still rather high. Many public and commercial health facilities offer free or significantly subsidized services, but social, cultural, economic, or health care service limits may prevent many women from using them.6\n\nBoth men and women can plan their family sizes and prevent unwanted pregnancies, which not only increase maternal mortality but can also cause distress and anxiety. Reliable contraception makes this possible. Women in the Gaza Strip, Palestine facing challenges in using contraceptives, including user and viewpoints of the providers. Family planning services were not expected because most Palestinian women who visited the clinic had already chosen their method of birth control, with decisions being made by their husbands.7–9 The primary motivation to improved access and support for women in the Middle East must be the experience growing up in the region and seeing firsthand the challenges and barriers women have when trying to obtain family planning. Challenges that impede the Middle East’s ability to get family planning services advancement in reaching family planning objectives, which exacerbates the region’s problems with gender equality and economic mobility. Prioritizing should be given to a number of important areas, such as lack of comprehensive education, healthcare infrastructure, economic restraints, religious influences, and stigma.10–12\n\nIn the Arab world, balancing population growth, social and economic development, and environmental resources will also be aided by reducing unmet demand. Of all the regions in the world, the Middle East and North Africa region has the worst freshwater deficit.13,14An analysis of Egypt’s 2008 DHS demonstrates that Egypt’s total fertility rate the number of births per woman during her lifetime would drop from 3.0 to 1. If women were able to successfully avoid having children as a result of unwanted pregnancies. 2.4 Unplanned pregnancies account for 14% of pregnancies in Egypt.15,16\n\nIn nations where the rate of unwanted pregnancies is higher, the effect of lowering it on fertility would be even more pronounced. According to a research by the Higher Population Council of Jordan, if Jordan’s unmet family planning requirement had been decreased to half in 2009, that year’s total number of unplanned births would have been decreased by 10,000, or 6% of all births.17Compared to other wealthy nations, Saudi Arabia has a higher birth rate and overall fertility rate, and research has shown a correlation between these high rates and underdevelopment. Due to the swift expansion of the Saudi Arabian economy, there is a growing demand for the use of contraception and birth spacing.18–21\n\nIn Lebanon, the overall count of births and cesarean sections is increasing.22 In Lebanon, the overall count of births and cesarean sections is increasing. There were 34 infant deaths for every 1000 live births, along with 23 births and 7 deaths per 1000 people. The population was rising at a pace of 1.6% per year, which was among the lowest in the Arab world. The 2.3 births were made by the average woman during her reproductive lifetime.23\n\nUnwanted births worldwide approximately 82% are caused by women who wish to prevent getting pregnant but are not utilizing an effective form of contraception.24 The Arab world has a high rate of unwanted pregnancies, which burdens people, families, healthcare systems, and social and economic advancement.25 A person’s ability to choose the quantity, timing, and spacing of their offspring is essential to preserving their reproductive rights. As described in numerous international agreements and human rights documents, reproductive rights stem from the fundamental rights to reproductive autonomy for all persons and couples, free from violence, compulsion, or discrimination. They cover rights related to getting married, starting a family, having children in a healthful manner, and being protected from HIV and other STDs.26\n\n\nMethods\n\nA descriptive and analytic (cross sectional) study, was conducted at primary health care centers in a six Arabic countries includes (Iraq, Lebanon, Jordan, Yamane, Egypt, and Saudi Arabia).women who were attending clinics for routine appointments and who met the inclusion criteria were requested to answer the questionnaire that was designed in a Google Form, and the questionnaire link was sent to them.\n\nNon probability (purposive sample) consist of (198) women, which were selected according to inclusion criteria that are women in reproductive age, primiparous and multiparous mothers, and mothers who attended primary healthcare centers. The mothers provided informed consent and agreed to participate.\n\nThe study sample size was calculated with a confidence interval of 85%, a population of 30 million women in reproductive age (defined as ages 15 to 49) in the six Arab countries that included in the study, and a 5% margin of error. The sample size was calculated as 208 using OpenEpi (Open Source Epidemiologic Statistics for Public Health).27\n\nA total of 208 mothers were included; however, 10 withdrew. The data of 198 participants were statistically analyzed. The inclusion criteria were mothers in reproductive age, primiparous and multiparous mothers, and mothers who visited primary healthcare centers. Samples were collected online and the questionnaire link was sent to mothers in six Arabic countries.\n\nThis study was conducted between January 2024 and July 2024. The questionnaire was developed by the authors based on a literature review and related articles and consisted of two main parts: socio-demographic characteristics of mothers includes: (age, level of education of women, occupation of woman, nationality), the second one consists of Questions to understanding the avoidance of Middle East women to use family planning methods is consist of (51) items which are divided in to three main domains first one is (effective domain) consist of (12) items, the second one is (behavioral domain) consist of (17) items, and the last one is (cognitive domain) consist of (22) items.28,29 The questionnaire was sent to a panel of experts to assess its content validity. To assess its reliability, a validated questionnaire was distributed to 20 mothers. Cronbach’s alpha was 0.768, indicating the questionnaire’s consistent reliability.\n\nFor the purpose of scoring the scale, three Likert scale was used and scored as follows: (1) never, (2), sometimes, and (3) always. The significant of each barrier in the scale was determined by calculating the range score for mean and determining the maximum and minimum score and rated into three levels: low= 1 – 1.66, moderate= 1.67 – 2.33, and high= 2.34 – 3.\n\nFor the purpose of analyzing data, the Statistical Package for Social Science (SPSS- version 24.0)30 was used through application of descriptive statistics which includes: frequencies, percentages, and mean scores which were used to describe the socio-demographic characteristics and also describe the severity of barrier’s significant.\n\nThe study protocol was approved by the Scientific Research Ethical Committee in the College of Nursing at the University of Baghdad Ref. No. 8: January 16, 2024. In addition, permission was obtained from the Iraqi Ministry of Health/Training and Developmental Department to collect data from primary healthcare centers in six Arabic countries. Ethical considerations, including the nature and aims of the study, voluntary participation, right to withdraw from participation, protection of confidentiality, privacy of the informants, use and publication of the study results, storage of data, and benefits of the study, were explained to the participants by the researcher. This information was conveyed in the human ethics form and verbally reinforced before data collection. The researcher informed the women about their rights of voluntarily participation, withdraw at any time, confidentiality, and privacy. Women who agreed to participate were asked to sign the consent form. Study ethical considerations including the nature and aims of the study, voluntary participation, the right to withdraw from participation, the protection of confidentiality and privacy of the informants, the use and publication of the study results, the storage of data, and benefits of the study were explained in writing to candidates. This information was conveyed in the human ethics application form. It was also verbally reinforced before the conduction of the interview.\n\n\nResults\n\nThe analysis of this Table 1 shows that women are with average age of 32.23 ± 7.9 years in which the highest percentage is seen with age group of 30-39 years (40.4%). Regarding level of education, the highest percentage is seen with 22.7% of those who graduated from institute or college. The nationality of women distributed equally from various countries; Iraq (16.7%), Lebanon (16.7%), Jordan (16.7%), Yemen (16.7%), Egypt (16.7%), and Saudi Arabia (16.7%).\n\nTable 2 indicates that women have high affective barrier to avoid uses family planning methods (total grand mean = 2.60); the mean scores indicate high among most of affective barrier except (Contraceptives can actually make intercourse seem more pleasurable) and (Contraceptives are not really necessary unless a couple has engaged in intercourse more than once) that show moderate.\n\nTable 3 reveals that women have high behavioral barriers to avoid uses family planning methods (total grand mean = 2.56); the mean scores indicate high among most of behavioral barriers except (After a sudden intercourse, I use an emergency contraceptive method to prevent pregnancy), (I would practice contraception even if my partner did not want me to) and (I prefer that my husband be receptive to the responsibility of using contraceptive methods) that show moderate.\n\nTable 4 depicts that women have high cognitive barriers to avoid uses family planning methods (total grand mean = 2.56); the mean scores indicate high among most of cognitive barrier except (I think that the natural method is effective in family planning), (I think implantation is good for family planning) and (I think it is better to have a tubal ligation to prevent childbearing) that show moderate.\n\n\nDiscussion\n\nTotal grand mean = 2.60 indicates that women have a high affective barrier to using family planning methods; mean scores are high for most affective barriers, with the exception of (Contraceptives can actually make intercourse seem more pleasurable) and (Contraceptives are not really necessary unless a couple has engaged in intercourse more than once) that show moderate.\n\nApproximately 17% of married women worldwide, or over 100 million women in less developed countries, would prefer not to get pregnant but are not utilizing family planning. Unwanted or pregnancies might result from unmet contraceptive needs. Which puts women, their families, and society at risks. Approximately 25% of pregnancies in less developed countries are unplanned.31challenges pertaining to reproduction can occasionally exist, such as (lack of sexual activity or prolonged intervals between sexual activity, fear of contraceptive side effects including bleeding, spotting, amenorrhea, or incidence of breast tumors or any other gynecological oncology). Furthermore, some women choose not to use contraceptives because they believe that they are not truly necessary until a couple has had multiple sexual encounters. This is especially true for women whose husbands work outside the home for a several days. The involvement of the husband frequently has a detrimental impact on women’s decisions to use or not use family planning methods. Instead, it pushes women to have a large number of children, particularly in rural countries where a large family is seen as a source of strength and pride for the father. In many cases the role of husband is negatively affected women’s decisions about use or abstain family planning methods. Rather the forces the women to have a lot of children, especially in rural societies that believe that the large number of children is a source of proud and strength for the father.\n\nThe population of Iraq has grown at an average yearly growth rate of 3% over the past three decades.32 Which, together with Yemen and Palestine, is regarded as one of the highest in the Region.33At the moment, 70% of people reside in cities.34 Women in their twenties of the overall population, 20% are between the ages of 15 and 49.35 With 22% of the population living below the federal poverty line and a comparatively high maternal mortality rate (50 deaths per 100,000 live births), poverty and unemployment are still high. There are disparities as well: the poverty rate doubles in rural areas, 22% of women are illiterate, and only 10% of the workforce is made up of women.36\n\nWomen have high behavioral barriers to abstention of family planning methods (total grand mean= 2.56); the mean scores indicate high among most of behavioral barriers except (After a sudden intercourse, I use an emergency contraceptive method to prevent pregnancy), (I would practice contraception even if my partner did not want me to) and (I prefer that my husband be receptive to the responsibility of using contraceptive methods) that show moderate.\n\nFamily planning service utilization decisions are influenced by a variety of service-related and demographic constraints. By comprehending and utilizing data on unmet need, policymakers and program managers can enhance family planning initiatives. Taking into account the traits of women and couples with unfulfilled needs and trying to remove barriers that keep them from selecting and utilizing family planning techniques.37 Sometimes the desire for the most effective methods creates barriers that prevent women from using family planning methods successfully, these barriers include the method’s induction of serious side effects, such as severe headaches, severe depression, severe bleeding, and extreme pain in the chest or abdomen. Some women also prefer natural methods because they think they are safe and effective, and some women avoid family planning methods because they are religiously prohibited from doing so or because they cannot access them cost free, and many of them are low-income. Together, these barriers force women to have unintended pregnancies, large families with lots of children, and sick mothers who are forced to care for their large families.\n\nConcerning barriers related to cognitive the study shows that women have high cognitive barriers to avoid uses family planning methods (total grand mean = 2.56); the mean scores indicate high among most of cognitive barrier except (I think that the natural method is effective in family planning), (I think implantation is good for family planning) and (I think it is better to have a tubal ligation to prevent childbearing) that show moderate.\n\nIn order to stabilize the global population, it is necessary to remove barriers that prevent all women from accessing high-quality contraceptive and family planning services. Prior studies on the obstacles to using FP services have emphasized the significance of focusing on factors other than physical access when analyzing obstacles resulting from administrative, cognitive, emotional, and cultural elements in addition to physical obstacles and method-specific obstacles.38\n\nThere are various types of reported barriers for both the discontinued group and the non-users. Cognitive, cultural and demographic barriers were the main barriers that lead to not using/discontinuation of family planning methods followed by barriers related to the method itself and reproductive barriers. The administrative and physical barriers were the least reported ones.39–41\n\nIn addition to social, cultural, and economic restrictions, Middle Eastern women continue to confront other obstacles in their quest for family planning services. This piece emphasizes the urgent necessity to remove these obstacles by disseminating promotional messaging. Providing counseling to women, particularly during postpartum visits, in order to dispel myths and assist them in making an informed decision. Providers in these fields should keep a variety of contraceptives on hand as well as offer counseling to help women and couples meet their contraceptive needs. This will allow women to select the methods that best suits their needs. Postpartum, breastfeeding, and menopausal women should receive counseling regarding their risk of getting pregnant, how to satisfy their family planning needs, and how to raise money to cover gaps in government programs. Governments can improve individual rights, growth population, and accomplish development goals particularly MDG 5, which calls for improved maternal health by reducing the unmet demand for family planning.6,42,43\n\n\nConclusions\n\nThe study concluded that there are many potential barriers which can negatively impact the Middle East women’s decision about their reproductive life includes affective, behavioral and cognitive barriers, depending on how they influence the decision-making process. The majority of barriers were impacted by understanding family planning, getting assistance from others (husbands, society, friends, etc.), adhering to social norms and culture, and giving family planning priority. Despite the fact that family planning faces several challenges in the Middle East, numerous governments and civil society organizations are working to find solutions to improve access to family planning services, promote education, hold candid conversations about reproductive health with local communities. Empowering the role of nurse in family planning to educate the couples about contraceptive methods and how to help them to choice the appropriate method.\n\nThe ethical approval was obtained from the Institutional Review Board (IRB) in College of Nursing at University of Baghdad with a reference number 8 in 16 January, 2024.\n\nAll participants provided informed written consent to participate in the study. The researcher informed the women about their rights of voluntarily participation, withdraw at any time, confidentiality, and privacy. Women who agreed to participate were asked to sign the consent form. Study ethical considerations including the nature and aims of the study, voluntary participation, the right to withdraw from participation, the protection of confidentiality and privacy of the informants, the use and publication of the study results, the storage of data, and benefits of the study were explained in writing to candidates. This information was conveyed in the human ethics application form. It was also verbally reinforced before the conduction of the interview.\n\nHawraa Hussein Ghafel: Writing – original draft, Supervision, Resources, Project administration, Investigation, Funding acquisition, Data curation, Conceptualization.",
"appendix": "Data availability\n\nFigshare: Understanding of Middle East Women’s Decisions and barriers to use Family Planning Methods, https://doi.org/10.6084/m9.figshare.26355775 29\n\nThis project contains the following extended data:\n\n• Data Data.xlsx\n\nFigshare: Questionnaires, https://doi.org/10.6084/m9.figshare.26355694 28\n\nThis project contains the following extended data:\n\n• Questionnaire in the English language\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 author appreciate the efforts and dedication of a Professor Dr. Sadeq Abdul Hussein Hassan, a professor Dr. Qahtan Qassem Mohammed (faculty members at College of Nursing, University of Baghdad) for their help. Without the women’s cooperation and assistance, the data could not have been gathered. The author greatly value their participation and cooperation.\n\n\nReferences\n\nUNFPA: women’s need for family planning in Arab countries.2012. Reference Source\n\nRoudi-Fahimi F, Monem AA: Unintended Pregnancies in the Middle East and North Africa. Washington, DC: PRB; 2010.\n\nJacqueline E: Darroch, Gilda Sedgh, and Haley Ball, Contraceptive Technologies: Responding to Women’s Needs. New York: Guttmacher Institute; 2011.\n\nRida MK, Ghafel HH: Correlation between Women’s Attitudes and Abstain (Used/Unused) Contraceptive Methods at Primary Health Care Centers in Baghdad City. Indian J. Forensic. Med. Toxicol. 2020; 15(1): 2309–2313. Publisher Full Text\n\nAnbesu EW, Aychiluhm SB, Alemayehu M: Women’s decisions regarding family planning use and its determinants in Ethiopia: A systematic review and meta-analysis protocol. PLoS One. 2022 Oct 13; 17(10): e0276128. Publisher Full Text\n\nAlrawi Y: Exploring barriers to family planning service utilization and uptake among women in Iraq. East Mediterr. Health J. 2021 Aug 26; 27(8): 818–825. PubMed Abstract | Publisher Full Text\n\nBöttcher B, Abu-El-Noor M, Abu-El-Noor N: Choices and services related to contraception in the Gaza strip, Palestine: perceptions of service users and providers. BMC Womens Health. 2019 Dec 19; 19(1): 165. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWulandari RD, Laksono AD, Matahari R: The Barrier to Contraceptive Use among Multiparous Women in Indonesia. Indian J. Community Med. 2021 Jul-Sep; 46(3): 479–483. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLaksono AD, Rohmah N, Megatsari H: Barriers for multiparous women to using long-term contraceptive methods in Southeast Asia: case study in Philippines and Indonesia. BMC Public Health. 2022 Jul 27; 22(1): 1425. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHaraoui S: Overcoming Barriers to Family Planning in the Middle East:FP2030.2024. Reference Source\n\nGhafel HH: Impact of Covid-19 Pandemic upon Iraqi women’s Commitment to Family Planning at Primary Health Care Centers in Baghdad City. J. Contemp. Med. Sci 2024; 10(2). Publisher Full Text\n\nGhafel HH: Impact of Covid-19 Pandemic upon Iraqi women’s Sexual and Reproductive Health at Primary Health Care Centers. J. Contemp. Med. Sci. 2023; 9(4): 255–261. Publisher Full Text\n\nWHO et al.: Trends in Maternal Mortality: 1990 to 2010: Estimates Developed by WHO, UNICEF, UNFPA, and the World Bank\n\nWorld Resources Institute: Earth Trends Data Tables: May 8, 2012 Freshwater ResourcesReference Source\n\nSpecial tabulations by Sara Bradley, ICF Macro, using the 2008 Egypt DHS.\n\nBradley SEK, Croft TN, Rutstein SO: The Impact of Contraceptive Failure on Unintended Births and Induced Abortions: Estimates and Strategies for Reduction. DHS Analytical Studies. 2011; 22.\n\nHigher Population Council, Reducing Discontinuation of Contraceptive Use and Unmet Need for Family Planning (Amman, Jordan: Higher Population Council, 2011): table 3 May 16, 2012. Reference Source\n\nAlselmi A: Family planning unmet need among women attending primary healthcare clinics in Western Region, Saudi Arabia. J. Family Med. Prim. Care. 2023 Jul; 12(7): 1276–1284. Epub 2023 Jul 14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMahfouz MS, Elmahdy M, Ryani MA, et al.: Contraceptive Use and the Associated Factors among Women of Reproductive Age in Jazan City, Saudi Arabia: A Cross-Sectional Survey. Int. J. Environ. Res. Public Health. 2023 Jan 2; 20(1): 843. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlkalash SH, Alessi SM, Alrizqi AA, et al.: Knowledge on, Attitude Toward, and Practice of Contraceptive Methods Among Females of Reproductive Age in Al-Qunfudah Governorate, Saudi Arabia. Cureus. 2023 Mar 23; 15(3): e36606. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlsharif SS, Abu Saeed RI, Alskhairi RF, et al.: Knowledge, Attitude, and Practice of Contraception Use Among Childbearing Women in Makkah Region, Saudi Arabia. Cureus. 2023 Feb 10; 15(2): e34848. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSammouri J, Khachfe HH, Fares MY, et al.: Deliveries in Lebanon, the Country with the Highest Refugee Density in the World: A Descriptive Review. Matern. Child Health J. 2024 Apr; 28(4): 601–608. Epub 2023 Nov 18. PubMed Abstract | Publisher Full Text\n\nFischbach MR: Spotlight: Lebanon. Popul Today. 1998 Jul-Aug; 26(7-8): 7. PubMed Abstract Reference Source\n\nDarroch JE, Sedgh G, Ball H: Contraceptive Technologies: Responding to Women’s Needs. New York: Guttmacher Institute; 2011.\n\nRoudi-Fahimi F, Monem AA: Unintended Pregnancies in the Middle East and North Africa. Washington, DC: PRB; 2010.\n\nUnited Nations Population Fund: Human Rights: 2012. The Foundation for UNFPA’s WorkReference Source\n\nRaosoft: Sample size calculator.2004. Reference Source\n\nGhafel HH: Questionnaires. Dataset. figshare. 2024. Publisher Full Text\n\nGhafel HH: Understanding of middle east women’s decisions and barriers to use family planning. Dataset. figshare. 2024. Publisher Full Text\n\nStatistical Package for Social Science (SPSS- version 24.0). http\n\nAshford L: Unmet need for family planning: 2012. Recent trends and their implications for programs. Washington DC: Population Reference Bureau. Reference Source\n\nWorld population dashboard. New York: United Nations Population Fund; 2019. Reference Source\n\nRoudi F, Monem AA, Ashford A, et al.: Women’s need for family planning in Arab countries. New York: United Nations Population Fund, Population Reference Bureau; 2012; 1–8.\n\nIraq urban population. New York: Trading Economics; 2016. Reference Source\n\nIraq: Virginia: The World Factbook.2019. Reference Source\n\nCountry cooperation strategy for WHO and Iraq. Cairo: World Health Organization; 2013.\n\nElzanaty K, Way A: Egypt Demographic and Health Survey. Cairo, Egypt: Ministry of Health and Population, National Population Council; 2005.\n\nElzanaty K, Way A: Egypt demographic and health survey. Cairo, Egypt: Ministry of Health and Population, National Population Council; 2005.\n\nEltomy EM, Saboula NE, Hussein AA: Barriers affecting utilization of family planning services among rural Egyptian women. WHO; 2013. Reference Source\n\nEvaluation of Women’s knowledge about Family Planning Methods at Omer Sawi Teaching Hospital. Iraqi National Journal of Nursing Specialties. 2023; 36(1): 49–58. Publisher Full Text\n\nFactors Affecting Birth Space Interval of Women Who Are Attending Primary Health Care Centers. Iraqi National Journal of Nursing Specialties. 2010; 23(2): 34–41. Publisher Full Text\n\nFactors Affecting Birth Space Interval of Women Who Are Attending Primary Health Care Centers. Iraqi National Journal of Nursing Specialties. 2010; 23(2): 34–41. Publisher Full Text\n\nBapolisi WA, Bisimwa G, Merten S: Barriers to family planning use in the Eastern Democratic Republic of the Congo: an application of the theory of planned behaviour using a longitudinal survey. BMJ Open. 2023 Feb 10; 13(2): e061564. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "327613",
"date": "11 Oct 2024",
"name": "Amy Tsui",
"expertise": [
"Reviewer Expertise Reproductive health behaviors"
],
"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\nAim: The study pursues an important topic, i.e., to understand cognitive, affective and behavioral factors inhibiting the decision to use contraception among Middle Eastern (ME) women. In reality the level of use of modern contraceptive methods in many Middle Eastern countries is quite robust. According to the UN’s World Contraceptive Use database for 2022, the six ME counties selected for this study have modern contraceptive prevalence rates (mCPR) for married women of childbearing age ranging from 56.9% (Egypt) to 24.4% (Saudi Arabia). The mCPR usually maximizes at 80% (e.g., China, Sweden) which indicates that at least one-fifth of the eligible female population will not use at any given time (due to infecundity, seeking to become pregnant, non-exposure). Thus, while mCPR may be low in some countries, use is not trivial. Also there is considerable reliance on withdrawal (considered a traditional method).\nDesign/Sample: The author relies on a convenience sample of 198 mothers attending clinics in Iraq, Lebanon, Jordan, Yemen, Saudi Arabia and Egypt. The sample, in addition to being purposive, is small (33 women per setting) and cannot represent the range of contraceptive experiences in these countries. More justification is needed as to why these six countries are included and not others, such as Syria, Irban, Oman, Qatar. An 85% confidence interval is very large for estimating these barriers; what was the initial “p” value used to calculate the needed sample size? A p of 0.5 with an alpha of 0.05 usually needs around 500 sample units and this is for one population.\nTheoretical framework for the 3 barrier domains: How did the author decide on “cognitive”, “affective” and “behavioral” domains? The author should define what each domain represents.\nAnalysis/Results: The question items in each domain set are plausible but require supporting literature. The Likert scale used has only 3 points and may not adequately differentiate a respondent’s attitude toward an item. In the study 1 = never, 2=sometimes, 3=always.\n\nMean values between 2 and 3 dominate; only 2 out of the total 51 items have a mean below 2.0. Likert scales usually have 5 points (strongly agree, agree, neutral/undecided, disagree, strongly disagree). Even though a Cronbach’s alpha value is given (presumably for all 51 items), there should be 3 alpha values, one for each domain. Analytically, with a sufficient sample size, the responses could be analyzed with principal components analysis to see if the items do load onto three factors and confirm the labels given. The descriptive analysis of means is difficult to interpret.\nDiscussion/Conclusions: This section should be limited to what has been empirically analyzed and not generalize beyond the findings.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-898
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https://f1000research.com/articles/13-897/v1
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06 Aug 24
|
{
"type": "Software Tool Article",
"title": "CINNAMON-GUI: Revolutionizing Pap Smear Analysis with CNN-Based Digital Pathology Image Classification",
"authors": [
"Luca Zammataro"
],
"abstract": "Background Medical imaging has seen significant advancements through machine learning, particularly convolutional neural networks (CNNs). These technologies have transformed the analysis of pathological images, enhancing the accuracy of diagnosing and classifying cellular anomalies. Digital pathology methodologies, including image analysis, have improved cervical cancer diagnostics. However, existing commercial platforms are often costly and restrictive, limiting customization and scalability.\n\nMethods CINNAMON-GUI is an open-source digital pathology tool based on CNNs for classifying Pap smear images. Transitioning to a Shiny app in Python, it offers enhanced user interface and interactivity. The application supports dynamic web interactions, advanced features for image analysis, and state-of-the-art CNN models tailored for digital pathology. Key features include intuitive UI components, real-time image and plot generation, memory-efficient data handling, and robust training capabilities with customizable CNN architectures. The tool also integrates with Labelme for defining regions of interest and allows testing on external biospecimens.\n\nResults Model A (seed 42, 100 epochs) and Model B (same architecture with adjusted augmentation parameters) were compared. Model A stabilized with training accuracy around 0.88 and validation accuracy around 0.913. Model B showed improved performance with training accuracy around 0.91 and validation accuracy around 0.95. Feature mapping highlighted critical morphological aspects, improving classification accuracy. Model B reduced misclassification errors significantly compared to Model A.\n\nConclusions CINNAMON-GUI demonstrates the potential of an open-source platform in digital pathology, providing transparency and collaborative opportunities. The tool enhances diagnostic accuracy through feature map analysis and optimized CNN training. Future development aims to extend its application to other cancer types, leveraging its dynamic and user-friendly interface for broader use in diagnostics.",
"keywords": [
"python",
"shiny",
"tensorflow",
"CNN",
"image-processing",
"digital-pathology",
"cervical-cancer",
"pap-smear"
],
"content": "Introduction\n\nCervical cancer is a significant cause of death for women worldwide. In 2020, there were approximately 604,000 new cases and 342,000 deaths.1 This type of cancer is closely linked to persistent infection by certain types of human papillomavirus (HPV), particularly HPV-16 and HPV-18, which account for about 70% of cervical cancer cases.2,3 The Pap test, also known as the Papanicolaou test, is a widely used screening test for the prevention and early detection of cervical cancer. It involves examining cells collected from the cervix’s surface to identify any abnormal cellular changes indicative of potential cancer or precancerous lesions.4 However, interpreting Pap test results can be subjective and reliant on the operator’s expertise. Additionally, the test’s accuracy can be affected by various factors, including sample quality and dyskeratotic cells, which can be challenging to interpret.5\n\nThe field of medical imaging has witnessed significant advancements due to the integration of machine learning techniques, particularly convolutional neural networks (CNNs).6 These technologies have transformed how pathological images are analyzed, enhancing accuracy in diagnosing and classifying cellular anomalies. Digital pathology methodologies based on image analysis have been developed to enhance the accuracy and effectiveness of cervical cancer diagnosis.7,8 Existing commercial platforms, like Hologic’s ThinPrep.\n\nImaging System, BD’s FocalPoint GS Imaging System or Roche’s CINtec PLUS Cytology, integrate machine learning techniques to automate and refine the analysis of Pap smear tests, aiming to increase the speed and reliability of diagnostics. However, these technologies often come embedded within proprietary systems that are costly and restrictive in terms of customization and scalability.\n\nIn this paper, we present Cinnamon-GUI (Convolutional Neural Network and Multimodal Learning with a Graphic User Interface), an open-source tool that allows users to configure sophisticated CNN architectures for classifying digital biomedical images. The tool is particularly designed for the cervical Pap smear dataset Sipakmed, a significant resource in cervical cancer research due to its comprehensive collection of high-quality images and associated clinical data.9\n\nCinnamon-GUI is a unique advancement in digital pathology, offering an open-source solution based on CNN for classifying Pap smear images. Its standout features include transparency, collaboration, and the ability for users to explore, modify, and tailor the code to their specific needs. Cinnamon-GUI is open-source approach not only invites the scientific community to actively contribute to its development but also fosters a sense of belonging and shared progress, enhancing its efficiency and applicability through feedback and updates.\n\n\nMethods\n\nCinnamon-GUI has transitioned to a Shiny app in Python, bringing several advantages, notably an enhanced user interface and improved interactivity. The Shiny framework10 allows for dynamic and responsive web applications, making it easier for users to interact with machine learning models and visualize results in real-time.\n\nThe application stands out for its advanced features that optimize the analysis of digital images, making it a powerful tool for the scientific community. One of its main features is using state-of-the-art TensorFlow11 convolutional neural networks (CNN) models which can recognize and classify complex patterns in pathological images, significantly improving diagnostic accuracy. Our implementation also makes extensive use of Python libraries such as Numpy,12 Scipy,13 Pandas,14 and Scikit-learn.15\n\nThe general structure of the CNN in Cinnamon-GUI, characterized by convolutional layers, four pooling layers, one flatten layer and two dense layers, can be illustrated by Figure 1.\n\n** This schematic illustrates two primary operational pathways within the platform: 1) Data Processing and Model Training Workflow, where users can load pickle files from datasets to train models and generate reports post-testing, and 2) Biospecimen Annotation and Analysis Workflow, where users can load annotated Pap smear images, with annotations applied using the integrated Labelme software. This workflow supports loading the corresponding JSON annotation files and converting them and the images into a pickle dataset format for subsequent cell type prediction and classification. Additionally, this pathway facilitates the creation and expansion of datasets, enhancing the utility of Cinnamon-GUI for diverse research applications.\n\nThe user interface of Cinnamon-GUI is designed to be intuitive and dynamic, facilitating workflow even for professionals without advanced technical expertise. Dynamic UI components allow users to interact easily with machine learning models and visualize results in real time.\n\nAnother distinctive feature of Cinnamon-GUI is the dynamic generation and display of images and plots. Using base64 encoding, the application efficiently manages memory usage, ensuring high performance even when analyzing large datasets.\n\nUpon startup, Cinnamon-GUI initializes a log file (log.txt) to record all activities and messages during the session. This logging system is integrated with a real-time notification system that informs users about the status and progress of various operations, such as model training, data augmentation, and image classification. This feature enhances transparency and traceability of the analysis process, keeping users informed about the ongoing tasks.\n\nThe application displays real-time progress during training, including a progress bar and status messages. The training process includes advanced features such as callbacks for early stopping and learning rate reduction based on validation loss. Early stopping prevents overfitting by stopping the training process when the model’s performance on a separate validation dataset stops improving. Learning rate reduction adjusts the learning rate during training to help the model converge to a better solution. These features significantly improve training efficiency. The trained model and log file are automatically saved to disk upon completion.\n\nThe Training Tab includes robust data augmentation capabilities that enhance the diversity of the training dataset and improve model generalization. Users can customize various augmentation parameters, including:\n\n• Rotation Range: Randomly rotates images within a specified degree range.\n\n• Width and Height Shift Range: Randomly shifts images horizontally and vertically.\n\n• Shear Range: Applies shearing transformations.\n\n• Zoom Range: Randomly zooms into images.\n\n• Horizontal and Vertical Flip: Flips images horizontally and vertically.\n\nThese augmentation techniques are applied in real-time during training, generating new variations of the images in each epoch.16\n\nFinally, Cinnamon-GUI offers advanced tools for image display and feature mapping. Users can select an image index to display the image and its predicted class. Additionally, feature mapping plots can be generated to visualize the activations of different layers in the model. The application generates tests on the testing dataset to evaluate model performance, comparing predicted labels with actual labels and providing detailed reports.\n\nThe Cinnamon-GUI’s feature mapping function, which involves mapping the various layers of the CNN through our software, makes identifying these pathological traits much more accessible.\n\nAs example of implementation, we use the Sipakmed Dataset (see Data and Software Availability). Although almost all the models we experimented with had the architecture, we conducted several tests to understand which parameters were involved in improving classification performance. These performances were evaluated based on the number of failures obtained through the evaluation of the testing datasets, trying to identify which cells the various models failed to classify correctly.\n\nWe will discuss two comparative models, which we will call A (2024.07.13-01.30.20-42) and B (2024.07.01-00.58.38-42). Models A and B are identical in terms of their architecture, and optimization algorithms: both the Models use Adam, which combines the benefits of two other extensions of stochastic gradient descent, Adaptive Gradient Algorithm (AdaGrad) and Root Mean Square Propagation.\n\nHowever, the two models present some differences in the parameter settings for image augmentation. Both models were configured with a seed of 42, thus ensuring identical training sets for training and the reproducibility of tests using the same testing dataset. The latter consists of 809 images, equally distributed among the five categorical classes of Sipakmed.\n\nModel A:\n\n• Parameters: seed 42, 100 epochs, test size 0.2, batch size 32, rotation_range=20, width_shift_range=0.5, height_shift_range=0.4, shear_range=0.4, zoom_range=0.5.\n\n• Performance:\n\n• Training accuracy: stabilizes around 0.88.\n\n• Validation accuracy: stabilizes around 0.913 with some fluctuations.\n\n• Training loss: stabilizes around 2.047.\n\n• Validation loss: stabilizes around 2.155.\n\n• Misclassification: 28 dyskeratotic cells misclassified as Koilocyte cells (Figure 3).\n\nModel B:\n\n• Parameters: seed 42, 100 epochs, test size 0.2, batch size 32, rotation range=20, width_shift_range=0.2, height_shift_range=0.2, shear_range=0.2, zoom_range=0.2.\n\n• Performance:\n\n• Training accuracy: stabilizes around 0.91.\n\n• Validation accuracy: stabilizes around 0.95 with more variability compared to training accuracy.\n\n• Training loss: stabilizes at 1.544.\n\n• Validation loss: stabilizes around 1.381.\n\n• Misclassification: Reduced total errors to 38, with dyskeratotic cell misclassifications down to 3 (Figure 4).\n\nThe CNN architecture chosen for classifying the Sipakmed dataset is detailed in Table 1.\n\n\n\n1. Clone the Cinnamon-GUI GitHub repository:\n\ngit clone https://github.com/lunanfoldomics/Cinnamon-GUI\n\n2. Create a virtual environment, and install required dependencies: follow the installation instructions from the GitHub repository\n\n3. Navigate to the project directory:\n\ncd Cinnamon-GUI/dashboard-tips\n\n4. Start the application:\n\npython cinnamon-gui.py\n\n5. Access the application in your browser:\n\nOpen your browser and navigate to ‘http://127.0.0.1:8000/’\n\n6. Workflows:\n\nThe Cinnamon-GUI platform offers two primary operational workflows. These workflows are designed to significantly enhance research efficiency and analytical accuracy in digital pathology studies, making the platform a valuable tool for researchers (Figure 1).\n\n\n\n1. Data Processing and Model Training Workflow: With its intuitive and user-friendly interface, this pathway empowers users to engage with machine learning. Users can easily import datasets stored as pickle files, a format that preserves the data structure, ensuring fidelity during loading. The workflow is designed around TensorFlow-based models, enabling users to train these models with their datasets or upload and use a pre-trained model.\n\nOnce the dataset is loaded into memory, it is normalized, and reshaped for processing. Additionally, a class definition file (TSV format) can be uploaded to define the classes used in the dataset, facilitating labeling and classification during model training and evaluation.\n\nUsers can configure and implement various customizable Convolutional Neural Network (CNN) architectures tailored to their specific needs through the Training Tab. The interface allows customization of multiple hyperparameters, including the number of convolutional layers, filters, kernel sizes, activation functions, and pooling layers. Users can add fully connected layers with customizable activation functions, dropout rates, and regularization techniques such as L1 and L2 (Figure 2).\n\nUsers can set various parameters for training the model, including number of epochs, batch size, learning rate, and data augmentation settings.\n\nThe workflow includes internal functions for image normalization and a suite of functions for randomly splitting the dataset into training and testing sets for CNN learning. Users can select from a wide range of seeds for random splitting via the scikit-learn package using a dedicated sliding bar in the GUI’s Training Tab. Users can also choose from a variety of optimization algorithms to train their models.\n\nOptionally, users can upload a pre-trained model, the architecture of which is summarized and displayed in a tabular format. This feature provides detailed information about each layer of the loaded model and its parameters, helping users better understand the structure of the model.\n\nA significant feature of this pathway is its reporting capability; after training models and conducting tests, users can generate comprehensive reports. These reports visualize performance metrics such as accuracy, loss over epochs, and more detailed statistical analyses, providing crucial insights into model behavior and efficacy.\n\n2. Biospecimen Annotation and Analysis Workflow: Tailored for researchers working with biomedical imagery, this workflow is crucial in dataset creation and expansion. It facilitates the loading and processing annotated Pap smear images in BMP format. Annotations are initially applied using Labelme,16 a versatile tool that allows detailed marking of cells, essential for accurate specimen identification. The platform supports importing JSON files containing these annotations, which are then converted along with the images into pickle format. This data format standardization simplifies the integration of images into the machine learning pipeline, which is used for cell-type prediction and classification.\n\nWhen operating in Biospecimen Annotation and Analysis, Cinnamon-GUI can become a tool for diagnosing the possible presence of cancerous cells in the evaluated specimen.\n\nFurthermore, this workflow is instrumental in enabling researchers to build robust, annotated image datasets that enhance the utility of Cinnamon-GUI across various research applications.\n\nThis interface allows users to adjust settings crucial for deep learning model training, such as seed value for reproducibility, data augmentation techniques (rotation, width and height shifts, shear, zoom, and horizontal flip), and other preprocessing options. Advanced settings include selecting optimizers, loss functions, and learning rate adjustments. Below, convolutional layer parameters such as filter count, kernel size, activation functions, and associated max-pooling layers are customizable along with dense layer configurations, regularization options (L1 and L2), and dropout rates, enabling precise control over the model's architecture and training dynamics.\n\n\nResults\n\nThe training accuracy for Model A increases rapidly in the initial epochs. Then, it stabilizes around 0.88, suggesting that the model learns from the training data but might not capture all the complexities. While slightly higher, the validation accuracy shows variability, indicating some instability. The training and validation losses for Model A indicate that the model is learning effectively but has room for improvement in generalization (Figure 3).\n\nA: Training dynamics over 100 epochs show training and validation accuracy and loss curves. The model achieves a training accuracy of 88.8% and a validation accuracy of 91.3%, with training and validation losses converging by the 100th epoch.\n\nB: Comparison of predicted versus actual counts of different cell types. The bar chart and accompanying table detail the count discrepancies across classes like Dyskeratocytes, Koilocytes, Metaplastic Cells, Parabasal Cells, and Superficial-Intermediate Cells, illustrating the model's predictive capabilities and areas for improvement.\n\nC: Scatter plot matrices represent the classification discrepancies for each cell type. Each plot filters data based on the predicted and actual class, highlighting specific images (by index) where discrepancies occur. This aids in visual error analysis and further model tuning.\n\nA deeper analysis of model A’s feature maps and neuron activations shows that dyskeratosis and koilocytosis can have overlapping features, such as abnormal nuclear shapes and sizes. Model A might need to emphasize features like circular patterns and textures in both cell types. The highlighted regions in the feature maps show strong activations around these patterns (data not shown). There might be insufficient training examples for dyskeratoses in the Sipakmed dataset, causing the model not to learn the distinctive features adequately. For example, suppose data augmentation techniques introduce more prevalent patterns in koilocytosis. In that case, the model might learn to associate these patterns more strongly with koilocytosis, even when they appear in dyskeratoses.\n\nTo improve CNN accuracy, we implemented the more balanced Model B, which demonstrates significant improvements. Reduced image augmentation parameters lead to better performance. The training and validation accuracies for Model B are higher than for Model A, and the losses are lower, indicating better generalization. The reduction in total errors and dyskeratotic cell misclassifications highlights the impact of optimized training data and model parameters (Figure 4).\n\nA: Training and validation performance over 100 epochs. The curves illustrate the model's training accuracy (top) stabilizing at 89.5% and validation accuracy (top) reaching 95.3%, with corresponding loss metrics (bottom) indicating good model convergence.\n\nB: Bar chart comparing the predicted versus actual counts for various cell types, including Dyskeratocytes, Koilocytes, Metaplastic Cells, Parabasal Cells, and Superficial-Intermediate Cells. The data demonstrate close alignment between predicted and actual counts, with a detailed breakdown in the accompanying table. Notably, the number of Dyskeratotic cells misclassified as Koilocytes has significantly decreased from 28 to 3, showcasing the model's improved specificity.\n\nC: Scatter plot matrices showing detailed discrepancies between predicted and actual classifications for each cell type. Each plot categorizes discrepancies by image index, allowing for targeted analysis of specific instances where the model's predictions deviate from actual classifications, facilitating focused diagnostic and model refinement efforts.\n\nUsing feature maps, we aim to discern the morphological aspects the CNN identified and utilized during training. Understanding these aspects allows us to isolate critical patterns, which could be fundamental for accurate classification criteria in pathology.\n\nWe will now present some observations derived from the feature mapping analyses. However, for editorial reasons, we will compare a superficial-intermediate cell, a koilocyte, and a dyskeratocyte from the Sipakmed dataset, classified using Model B. The feature maps can indicate that the CNN successfully captured various subcellular details, such as the nucleus’s structure and the cytoplasm’s distribution.\n\nThe cell in Figure 5 has been classified as a superficial intermediate, a type of epithelial cell frequently present in Pap smear samples. The cell has a relatively small central nucleus, while the cytoplasm appears abundant and evenly distributed. The feature map analysis of Layer 1 (Batch Normalization) plays a crucial role in distinguishing the cell’s contours, particularly the edges. This underscores the early layers’ ability to capture the essential characteristics of the cell’s shape and border. Layers 11 (Max Pooling) further emphasizes critical regions of the cytoplasm and nucleus, with reduced noise and better definition of subcellular features. The convolutions in this layer capture finer details, such as texture variations that could be related to chromatin structure or the presence of vacuoles.\n\nTop left: Original microscopy image of the cell classified as superficial intermediate due to its small central nucleus and abundant cytoplasm. Top right: Feature maps at various convolutional layers highlighting critical regions and texture variations. Bottom panels: Activation patterns in the dense layers demonstrate how neural network processing layers contribute to the final classification decision. The early layer visualizations emphasize the cell's contours and internal textures, while the deeper layers distill these features into a final diagnostic insight.\n\nThe activations in the dense layers (flatten, Dense, Dropout) provide insight into the network’s decision-making process. They show how the network has condensed the information collected in the previous layers to make the final classification. High activations in certain regions indicate that specific features are essential for classifying as a superficial intermediate cell. (Figure 5).\n\nThe feature mapping can distinguish dyskeratocytes from koilocytes, which are prodromal cells of a transformation into dyskeratocytes. Koilocytes (from the Greek, meaning “hollow vessel”) are squamous cells infected productively with episomal human papillomavirus (HPV) that exhibit morphological alterations indicative of HPV infection. Koilocytosis is pathognomonic, though not required, for diagnosing low-grade squamous intraepithelial lesions (LSIL). The main morphological alterations observed in koilocytosis include Karyolysis (chromatin within the nucleus appears fragmented and dispersed, giving the nucleus a translucent or granular appearance), demonstrating that the E5 and E6 proteins from HPV cooperate to induce koilocyte formation, hinting at nuclear alterations similar to Karyolysis.17 Other alterations include nuclear hypertrophy (enlarged nucleus with increased chromatin density), nuclear enlargement, and hyperchromasia.18 Koilocytes are indeed characterized by an increased nuclear/cytoplasmic ratio (the nucleus occupies more of the cellular space than the cytoplasm).\n\nThe cell in Figure 6 represents a koilocyte correctly identified by Cinnamon-GUI; the nucleus is characteristically irregular and shows a clear central area with a denser peripheral zone known as the perinuclear halo.17,18 This can be because of the HPV, which induces irregular peripheral collapse of keratins as an effect of the HPV’s E4 gene induction, leaving a clear space around the nucleus.19\n\nTop left: Original microscopy image showcasing the characteristic irregular nucleus with a clear central area and a denser perinuclear halo indicative of HPV effect. Top right: Close-up of the perinuclear halo emphasized in feature maps. Middle panels: Visualizations from Convolutional Layers 3 and 9 highlight the complex nuclear and cytoplasmic features, including the perinuclear halo and cytoplasmic vacuolations. Bottom panels: Neuronal activation patterns in the dense layers (flatten, dense layers 2 and 3).\n\nThe feature maps in Layer 3 (Convolutional) show complexity, with a detailed representation of nuclear and cytoplasmic features. The perinuclear halo and nuclear irregularities are evident. Layer 9 (Convolutional) captures critical features, such as the perinuclear halo and cytoplasmic vacuolations. The CNN neuronal activations are highly specific to these patterns. As for the Superficial intermediate mentioned above, the final dense layers show a distribution of activations reflecting the model’s learning (Figure 6).\n\nFinally, the image in Figure 7 shows a correctly identified dyskeratotic cell. The cell’s nucleus appears significantly altered with an irregular shape, and it is dark and compact. The cytoplasm is dense and irregular, often with evident inclusions. Dyskeratotic cells tend to show more intense and granular cytoplasm than normal cells.\n\nTop left: Microscopy image of the dyskeratotic cell displaying its characteristic irregular, dark, and compact nucleus alongside a dense and irregular cytoplasm with visible inclusions. Top right and middle: Feature maps from the convolutional and batch normalization layers highlight the cell's nuclear irregularities and cytoplasmic density variations, emphasizing the borders and internal textures. Bottom: Activation patterns from the dense layers demonstrate the CNN's ability to discern and focus on critical morphological features that help distinguish dyskeratotic cells from other cell types, showcasing intricate nuclear and cytoplasmic details crucial for accurate classification.\n\nThe first layers (Batch Normalization and Max Pooling) show the detection of the cell’s basic contours. The patterns highlighted here focus on the cell’s borders and intensity differences in the cytoplasm.\n\nThe intermediate layers (Convolutional and Batch Normalization) focus more on nuclear features. The model highlights areas with intensity variations in the nucleus, hyperchromatic and irregularly shaped, with varying chromatin density, indicative of potential precancerous changes. The feature maps in the more advanced layers become more complex, showing intricate patterns that combine nuclear and cytoplasmic contours. These layers allow the model to distinguish dyskeratotic cells from other cell types (Figure 7).\n\n\nConclusions/Discussion\n\nAlthough various machine learning-based solutions for digital pathology exist, the effort to build an utterly open-source platform for physicians and researchers can represent an additional diagnostic tool for the progress of digital pathology. Often, current software solutions compete, striving to propose increasingly accurate solutions for early cancer diagnosis. However, most of the time, it is necessary to deal with the limitations of available datasets. These limitations pose challenges even for the most sophisticated machine learning algorithms, not to mention the risk of overfitting on relatively small datasets, such as Sipakmed.\n\nConversely, Cinnamon-GUI proves to be an extremely transparent tool that aims to identify the real problems of the used datasets through the analysis of feature maps, alerting researchers about the quality of predictions. Through our experience, we have, for example, understood that more issues related to inaccurate classification than the chosen CNN architecture could depend on how we attempt to extend the original dataset through image augmentation. We have realized that this is an essential part of modern machine learning and that these techniques must be used cautiously.\n\nThe analysis of the feature maps and neuron activations suggests that if not accurately trained, the CNN model can confuse specific patterns present in both dyskeratoses and superficial-intermediate cells. To improve classification accuracy, it is crucial to strengthen training by playing with image augmentation settings and refining the model architecture to capture distinctive features better.\n\nWe have demonstrated how image augmentation can benefit a CNN model’s performance improvement when applied in “small doses” and that it may not be necessary to hyper-transform the original dataset. Instead, reducing parameters such as width and height shift can yield better results. Indeed, using Model B, we decreased the number of errors significantly, demonstrating the critical impact of fine-tuning augmentation settings on model performance and accuracy.\n\nWith the help of feature mapping, we understand the role of the early layers of the network, which are particularly effective in reinforcing contours and identifying the general shape of the cell. The subsequent and dense layers can capture fine details and texture differences crucial for accurate classification. The activation peaks indicate the most significant features the model used to make the classification.\n\nCinnamon-GUI, with its fully interactive interface, controls, and extreme ease of use, along with its accurate plots, represents a user-friendly tool in the field of Digital Pathology. It allows even non-experts to manipulate complex CNN architectures without any programming experience, empowering them to contribute to the field. Although the CNN models implemented within the code are limited to four convolutional layers and four pooling layers, the number of configurations that can be explored with our tool is vast, giving users confidence in their ability to explore and experiment.\n\nAnother powerful feature of Cinnamon-GUI is the ability to import external specimens and build new datasets using a manual annotation system based on the LabelMe software.\n\nCinnamon-GUI can extend its training capabilities using external datasets provided by the user or be limited to making the best possible predictions and classifications when used as a query system.\n\nAnother necessary functionality is multimodal learning, which integrates various data types to enhance analysis accuracy. Although this capability is intended only for research purposes, it represents a significant step towards a more comprehensive understanding of pathological conditions through analyzing heterogeneous data. We believe that the use of Cinnamon-GUI is not limited to the analysis of Pap smears alone. We are working towards making Cinnamon-GUI a powerful platform for the early diagnosis of many other types of cancers in the future, instilling hope and optimism in the potential impact of our work.",
"appendix": "Data and software availability\n\n\n\n• Source code available from: https://github.com/lunanfoldomics/Cinnamon-GUI\n\n• Archived software: https://doi.org/10.5281/zenodo.13109219\n\n• License: OSI approved open license software is under GNU Affero General Public License v3.0. SPDX-License-Identifier: AGPL-3.0-only\n\nThe Sipakmed database, 9 which consists of 4049 color images of cells from cervical pap smears, represents a vital example of this tool. Images have been classified into five cellular subclasses: Superficial-Intermediate Cells, Parabasal Cells, Metaplastic Cells, Koilocytes, and Dyskeratocytes. For our work, the database was restructured into a numpy array and subsequently inserted into a Pandas DataFrame, with each row corresponding to a sequence of 65536 pixels, each represented by an RGB triplet for color and associated with an output label. Once loaded into a NumPy vector, the images are reshaped into 256×256 matrices. Once the Sipakmed dataset is downloaded, it needs to be unzipped into a directory, which we might call “sipakmed.” The main directory structure of SipakMed is not particularly complex, but it is essential to understand where the images are located within the five cellular categories to correctly construct the pickle file. Therefore, a script must be generated to search for images within the sipakmed directory and generate the pickle file.\n\nA pickle version of Sipakmed is downloadable from here: https://www.kaggle.com/datasets/lucazammataro/sipakmed-dataset-for-cinnamon-gui\n\nThe pre-trained Model B described in the paper is downloadable from here: https://www.kaggle.com/datasets/lucazammataro/cinnamon-gui-model-b-sipakmed/data\n\nYou can create a Pickle Training Dataset from Sipakmed, downloading it from https://www.cs.uoi.gr/~marina/sipakmed.html\n\n\nAcknowledgement\n\nThe author declares that Lunan Foldomics LLC, may potentially benefit from the research findings reported in this article.\n\n\nReferences\n\nSung H, Ferlay J, Siegel RL, et al.: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021 May; 71(3): 209–249. PubMed Abstract | Publisher Full Text\n\nZammataro L, Lopez S, Bellone S, et al.: Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proc. Natl. Acad. Sci. USA. 2019 Nov; 116(45): 22730–22736. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWalboomers JM, Jacobs MV, Manos MM, et al.: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J. Pathol. 1999 Sep; 189(1): 12–19. Publisher Full Text\n\nPapanicolaou GN, Traut HF: The Diagnostic Value of Vaginal Smears in Carcinoma of the Uterus**This study has been aided by the Commonwealth Fund. Presented before the New York Obstetrical Society, March 11, 1941. Am. J. Obstet. Gynecol. 1941; 42(2): 193–206. Publisher Full Text Reference Source\n\nWalavalkar V, Tommet D, Fischer AH, et al.: Evidence for increasing usage of low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) Pap test interpretations. Cancer Cytopathol. 2014 Feb; 122(2): 123–127. PubMed Abstract | Publisher Full Text\n\nZammataro L, Rovetta S, Greco D: MEDIGUI-ConvNet–Interactive Architecture Combining the Power of Convolutional Neural Networks and Medical Imaging. INI-DH 2024: Workshop on Innovative Interfaces in Digital Healthcare, in conjunction with International Conference on Advanced Visual Interfaces. 2024; pp. 3–7.\n\nAlsubai S, Alqahtani A, Sha M, et al.: Privacy Preserved Cervical Cancer Detection Using Convolutional Neural Networks Applied to Pap Smear Images. Comput. Math. Methods Med. 2023; 2023: 9676206–9676208. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRahaman MM, Li C, Yao Y, et al.: DeepCervix: A deep learning-based framework for the classification of cervical cells using hybrid deep feature fusion techniques. Comput. Biol. Med. 2021; 136: 104649. PubMed Abstract | Publisher Full Text Reference Source\n\nPlissiti M, Dimitrakopoulos P, Sfikas G, et al.: Sipakmed: A New Dataset for Feature and Image Based Classification of Normal and Pathological Cervical Cells in Pap Smear Images.2018; pp. 3144–3148.\n\nDevelopment team: Shiny for Python.2024. Reference Source\n\nAbadi M, Agarwal A, Barham P, et al.: TensorFlow: Large-Scale Machine Learning on Heterogeneous Systems.2015. Reference Source\n\nHarris CR, Millman KJ, van der Walt SJ , et al.: Array programming with NumPy. Nature. 2020 Sep; 585(7825): 357–362. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVirtanen P, Gommers R, Oliphant TE, et al.: SciPy 1.0: Fundamental Algorithms for Scientific Computing in Python. Nat. Methods. 2020; 17: 261–272. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcKinney W: Data structures for statistical computing in python. Proceedings of the 9th Python in Science Conference. 2010; pp. 51–56. others.\n\nPedregosa F, Varoquaux G, Gramfort A, et al.: Scikit-learn: Machine learning in Python. J. Mach. Learn. Res. 2011; 12(Oct): 2825–2830.\n\nWada K: Labelme: Image Polygonal Annotation with Python.Reference Source\n\nKrawczyk E, Suprynowicz F, Liu X, et al.: Koilocytosis: a cooperative interaction between the human papillomavirus E5 and E6 oncoproteins. Am. J. Pathol. 2008; 173(3): 682–688. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLawson J, Glenn W, Heng B, et al.: Koilocytes indicate a role for human papilloma virus in breast cancer. Br. J. Cancer. 2009; 101: 1351–1356. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLhee MJ, Cha YJ, Bae JM, et al.: Diagnostic Algorithm to Reflect Regressive Changes of Human Papilloma Virus in Tissue Biopsies. Yonsei Med. J. 2014; 55: 331–338. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "312178",
"date": "09 Oct 2024",
"name": "Fabio Grizzi",
"expertise": [
"Reviewer Expertise My research focuses on tumor complexity and the interactions between tumor cells and both the innate and adaptive immune systems. This includes exploring non-linearity",
"chaos theory",
"fractals",
"and AI-based computer algorithms within the biological context."
],
"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\nLuca Zammataro's article marks a significant advancement in the adoption of appropriate tools for analyzing cytological and histopathological entities, which are often challenging to assess objectively through microscopy alone. The proposed tool, Cinnamon-GUI (CINNAMON-GUI), highlights the potential of an open-source platform in digital pathology, offering both transparency and collaborative opportunities. This tool improves diagnostic accuracy by utilizing feature map analysis and optimized CNN training. Future developments aim to expand its application to other cancer types, broadening its role in diagnostics through its dynamic and user-friendly interface. While Zammataro introduces the tool for classifying Pap smear images, its underlying principles can be applied to other clinical challenges. This manuscript is highly recommended for researchers focused on computer-aided image analysis systems in their work.\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": []
},
{
"id": "349037",
"date": "02 Jan 2025",
"name": "Gabriella Casalino",
"expertise": [
"Reviewer Expertise I work in computational intelligence",
"specializing in methods for intelligent analysis. My primary focus lies in the medical domain",
"where I have experience with a diverse range of medical data",
"including omics",
"acoustic features",
"vital parameters",
"video",
"and signal processing."
],
"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 \"CINNAMON-GUI: Revolutionizing Pap Smear Analysis with CNN-Based Digital Pathology Image Classification\" by Luca Zammataro presents an innovative open-source tool to improve the classification and diagnosis of Pap smear images. CINNAMON-GUI uses convolutional neural networks (CNNs) to address challenges in digital pathology, particularly in cervical cancer diagnostics. It combines sophisticated machine learning techniques with an interactive, user-friendly interface to make complex image processing accessible even to non-experts. One of the key strengths of the work is its open-source nature, fostering collaboration and customization within the medical and scientific communities. CINNAMON-GUI offers real-time interactivity, allowing users to visualize and understand classification results and analyze CNN layers to gain deeper insights into image features. The application is designed to support non-expert users while addressing a critical medical challenge, enhancing trustworthiness through transparency and adaptability. The capability to annotate, analyze, and integrate various datasets makes it a highly versatile tool. Including dynamic UI components and integrating with external software like Labelme further enriches its usability. Although the interface assumes some familiarity with the structure of deep neural networks, a potential limitation is its reliance on users' technical knowledge for customization. An additional layer of abstraction that provides default settings for absolute beginners could enhance accessibility. This would allow users with no technical expertise to benefit from the tool while gradually understanding its capabilities. Overall, this work is valuable to digital pathology and medical image analysis. Its potential to support the diagnosis of other pathologies in the future, coupled with the prospect of natural language explanations for identified regions, holds promise for broader adoption and impact. By prioritizing transparency, collaboration, and ease of use, CINNAMON-GUI is well-positioned to drive medical diagnostics and research advancements.\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": []
}
] | 1
|
https://f1000research.com/articles/13-897
|
https://f1000research.com/articles/13-896/v1
|
06 Aug 24
|
{
"type": "Research Article",
"title": "The developing of prosody in infants: a longitudinal study over the first 16 months of infant life",
"authors": [
"Valeria D'Aloia",
"Paola Zanchi",
"Maria Grazia Mada Logrieco",
"Ilenia Passaquindici",
"Riccardo Palumbo",
"Francesca Lionetti",
"Maria Spinelli",
"Mirco Fasolo",
"Paola Zanchi",
"Maria Grazia Mada Logrieco",
"Ilenia Passaquindici",
"Riccardo Palumbo",
"Francesca Lionetti",
"Maria Spinelli",
"Mirco Fasolo"
],
"abstract": "Background The acquisition and development of prosodic aspects of vocal intonation are of special interest within the larger context of language acquisition.\n\nMethod The present study explored the developmental trajectories of infant prosodic abilities from 4 to 16 months of life with an intensive time points assessment. Several aspects were considered: an acoustic analysis of infant vocal productions with specific software, the analyses of all the prosodic variables associated with the fundamental frequency (F0 mean, F0 range, and F0 final contours), the individual variability and the complexity of the vocal productions of the infants.\n\nResults The multi-level analysis evidenced specific prosodic developmental trajectories that differ for the different kind of vocal productions since the first months of life.\n\nConclusions The findings suggest that in the second half of the first year of life infants show an intonational repertoire that may help manage interactions with their caregiver and that individual variability has to be taken in consideration when assessing infants’ prosody.",
"keywords": [
"Prosody development",
"Fundamental Frequency",
"Multi-level analysis",
"Babbling",
"Infants"
],
"content": "Introduction\n\nEarly infants’ vocal productions form the basis for language development and are important social signals that stimulate caregiver response, which in turn facilitates the development of phonology and speech (Goldstein et al. 2009; Spinelli et al., 2017). Research on pre-linguistic vocalizations of typically developing infants has focused mostly on the segmental and syllabic aspects of spontaneous vocal productions. Fewer scholars focused their attention on supra-segmental aspects of infant vocalizations, including variables that measure prosodic aspects of vocal intonation such as those related to the pitch, usually measured through the fundamental frequency (F0). These prosodic features of language convey grammatical and pragmatic meaning as well as emotional or affect intent, and highlight particular elements of the utterance (Crystal, 1978; Gleitman et al., 1988; Wells et al., 2004). The development of prosody is of special interest within the larger context of language acquisition, because it is among the earliest aspects of speech to be acquired (Esteve-Gibert & Prieto, 2018) and is strictly linked to the maturity of the vocal tract (Kahane & Kahn, 1984). It is well known that infants are sensitive to prosodic information from a very early age due to their prenatal exposure to speech (Gervain, 2015) and therefore are able to understand the prosodic features of parental speech since the first months of life (De Carvalho et al., 2019; Fisher & Tokura, 1996; Soderstrom et al., 2008) and can manage to imitate the prosody of parental speech, for instance, by adapting their F0 features to match that of the parents (Gratier & Devouche, 2011; Ko et al., 2016; McRoberts & Best, 1997; Papoušek & Papoušek, 1989).\n\nAt birth, the infant’s vocal tract is not completely developed. Consequently, infant vocal expressions have different sounds and different melodies than adult ones (Astruc et al., 2013). Some authors reported much more reduced pitch range in children than in adults, and that children acquire falling tones first and final rising tones much later (Snow, 2004; Wells et al., 2004). The differences between infants and adults evidenced in the first stages of phonetic development have been linked to the difficulties in controlling the vocal tract. Specifically, Lieberman (1967) assumed that infants do not precisely control the tension of their laryngeal muscles once phonation starts. The child merely maintains the tension of the laryngeal muscles at or near the tension that they had as phonation started, and gradually rose from the start of phonation to either level of slightly falling “plateau”. For this reason, the majority of the breath-groups terminate with falling fundamental frequency contour. However, cross-linguistic differences have been reported, with the presence, for example, of rising contours evidenced in infancy in languages other than English (Esteve-Gibert & Prieto, 2013; Prieto et al., 2012; Whalen et al., 1991).\n\nTo our knowledge, only few data are now available considering the prosodic characteristics of the first infants’ vocal productions. The first of these was conducted by D’Odorico (1984), who acoustically analysed the cry and non-cry vocalizations produced by four Italian infants. The results of this study showed that cry vocalization produced in different context are acoustically different and that there are similarities in the acoustic properties of cry and not-cry vocalization produced in the same context. These results were later confirmed by D’Odorico and Franco (1991), who investigated the suprasegmental features of the vocalizations produced during social interaction by five Italian children from 4 to 11 months of age. Indeed, different patterns of non-segmental features were found in sounds produced in different contexts.\n\nConsidering the scarce data on Italian and the importance of cross-linguistic comparison on language development, the main aim of this study is to explore how Italian infants develop intonational abilities in the first 16 months of life, focusing on a detailed analysis of the infants’ pitch, in terms of F0 mean, F0 range and F0 final contours. Moreover, differently from other studies on this topic, comparing infants’ prosodic development to a mature adult model, the present study aims to give a broad picture of the longitudinal development of intonational repertory of children’s spontaneous productions, from 4 to 16 months of age.\n\nA summary of the main studies available on the intonation development during the first two years of life is reported in Table 1, available in the Open Science Framework repository as extended data; doi: https://doi.org/10.17605/OSF.IO/738W2. The main focus is on the examination of F0 related aspects (F0 mean, F0 range and F0 final contours) of non-distress spontaneous productions, excluding studies who examined distress productions such as cry and whining (Mampe et al., 2009; Rothgänger, 2003; Zanchi et al., 2016b).\n\nAmong the F0-related prosodic variables, the most widely studied is the fundamental frequency mean value (F0 mean), that represents the rate of vibrations of the vocal cords within the larynx and reflects pitch variations of the voice. One of the first reviews on the developmental changes in the F0 mean from birth to adulthood, made by Kent (1976), showed that F0 mean is higher at birth and gradually decreases until it reaches adult levels. However, the studies included in the review were very few. Some of the studies reported in Table 1 (refer to extended data in the Open Science Framework repository) showed the same descending pattern from birth to the second year of life for F0 mean (Amano et al., 2006; Robb & Saxman, 1985; Rothgänger, 2003). Flax, Lahey, Harris, and Boothroyd (1991) found that 2 out of 3 children showed a reduction in F0 mean between the onset of words and 50-words period. This decrease is explained as reflecting the gradual maturation of the vocal tract and the development of infant ability to control the voice.\n\nNonetheless, other scholars failed to find significant changes in F0 mean over time (Iyer & Oller, 2008; Robb et al., 1989). Laufer and Horii (1977) measured infants’ productions every two weeks during the first six months of life and found that F0 mean values slightly fluctuated. Amano et al. (2006) argued that the main reason why some studies did not find a decrease in the F0 mean values was that speech samples were collected over periods that were too short to catch this effect. Lastly, there is only one author to our knowledge who found the opposite pattern. Fairbanks (1942) reported an increase during the first five months of infant life, followed by stabilization.\n\nEven more contrasting findings have been presented about developmental trajectories of F0 range, namely the difference between the maximum and the minimum pitches produced within the utterance. F0 range represents the ability of infants to vary the intonation and to make the production more communicative and attractive for the listener (Amano et al. 2006). Amano et al. (2006) found an increase of F0 range after the onset of two-word utterances and hypothesized that, as infants grow up, they acquire the ability to vary the fundamental frequency of the voice within a production according to the increase of their communicative abilities. Similarly, Snow (2004) found that 4-years-old children showed a wider F0 range than 1-year-old infants. Nonetheless Snow and Ertmer (2012) reported that, in their sample, 10 out of 12 typically developing infants showed a decrease in F0 range between 3 and 9 months. In a first study, Robb and Saxman (1985) found a decrease of the between-utterances F0 range between 11 and 25 months, while, in a second study (Robb et al., 1989), they failed to find changes over time. Furthermore, Laufer and Horii (1977) found a slight decrease in within utterance F0 range during the first four months of life and a minor increase after the 4th month. To sum up, the developmental trajectories of the within productions F0 range is unclear.\n\nAnother prosodic variable that plays an important role in prosodic development is the F0 contour, intended as the shape of pitch (F0) variations within the utterance, which conveys a specific melody to the vocal production. F0 contour may increase from the beginning to the end of the production (rising F0 contour), decrease (falling F0 contour), or not significantly vary (level or flat F0 contour). The direction of these contours, especially of the F0 final contours, is considered fundamental in providing the pragmatic meaning of the vocal production. In most of the languages, falling final contours are typical of statements and labelling, while rising final contours are especially used with interrogative utterances (for Italian see for example Sorianello, 2021). Many scholars agree that infants start to use F0 final contours early to express intentions. For example, Prieto et al. (2012), Prieto & Vanrell (2007) and Esteve-Gibert and Prieto (2013) showed evidence that since the first year of life Catalan and Spanish infants, similarly to adults, are able to variate F0 final contours in order to signal pragmatic meanings, even before they can produce words. Several studies, mostly conducted in English speaking countries, agree that the majority of the productions of infants have falling contours (Fox, 1990), while rising contours are rare (see for example Kent & Murray, 1982, and Robb et al., 1989) and more frequent in adults (Cruttenden, 1997) and preschoolers (Snow, 2004). As stated above, according to Lieberman (1967), the falling contour is considered more natural and simpler than the rising contour without implying the infant’s intentionality. According to Lieberman hypothesis, rising patterns, by being contingent on language experience rather than physiological constraints, stabilize at a later stage of language acquisition. More recently, Snow (2006) found that the development of falling and rising patterns is not linear and follows a U-shaped trajectory. Both falling and rising contours are frequent and well expressed until nine months, when their quality decreases. After a period of stabilization, both these contours reach the same quality observed before the regression period at around 18 months. The author explained this results pointing out that intonation is controlled by physiology in the earliest stage (before nine months of age), but later the tones come under linguistic control. So, the regression could be due to a linguistic reorganization of speech and the U shape shows a shift of intonation from a pre-intentional to an intentional stage. Despite, these two main theoretical explanations, empirical studies that examined the frequency of F0 final contours trajectories over time found inconsistent results. Many of them (see, for example, Flax et al., 1991 and Murry et al., 1983) failed to find variations in the percentages of rising and falling contours over time. Fox (1990) found, consistently between the 3rd and the 9th month, a prevalence of 82% of falling final contours. On the contrary, Robb et al. (1989) found that the less frequently occurring F0 final contours were falling-rising and rising contours (comprising the 6% of all the vocalizations), and this percentage was constant, independently of lexicon size, throughout the first two years.\n\nTo sum up, the studies on the development of F0 features over the first years of life failed to give a clear and homogeneous picture, mainly because comparing these studies is difficult. First, the differences among languages, which could lead to different intonation features and developmental trajectories. Second, there are wide differences in the age ranges considered, in the number of longitudinal sessions and many other methodological aspects. For example, the types of infants’ vocal production included in the analyses (whether cry-like or squeal-like vocalizations were included in the analyses or only syllabic-like vocalizations), the tools used for the analyses of speech spectrograms (old studies used visual inspections of the spectrograms to measure values of F0 and are therefore less reliable than modern analyses run with ad hoc programs), and the study design (with longitudinal and cross-sectional analyses leading to different findings due to the variability among the participants).\n\nMoreover, an important issue raised by some of the reported studies is the presence of variability among infants, which affects both F0 values and age-related changes that occur in infants’ voices. Laufer and Horii (1977) described the F0 mean fluctuating from month to month with each infant presenting a specific pattern of change. Flax et al. (1991) found that three infants out of three showed different F0 range change patterns, with one child not varying at all in this period. Kent and Murray (1982) found a prevalence of F0 falling contours all over the age range considered, 3-6-9 months, but pointed out high intra- and inter-individual variability in the production of rising contours at one point in time as well as over time. Other authors agreed that differences among infants are present (Amano et al., 2006), but the restricted number of participants or number of sessions made it difficult to check this hypothesis. This has implications for the design of the study, for a greater number of participants need to be studied, and for the analyses, since participants variance has to be considered.\n\nMoreover, the reported studies mainly considered all the productions or only one specific type of production, without making comparisons among them (see Table 1 in the extended data in the Open Science Framework repository). Robb et al. (1989) recorded on 12 successive occasions the utterances of seven infants in the 8–26-month age period investigating the F0 mean of monosyllabic and bi-syllabic utterances. They found similar F0 mean values between the two productions but a tendency for monosyllables to have a greater F0 range than bi-syllables for all the participants except one child. Moreover, this tendency remained stable across the first two years of life. On the contrary, Snow (2004) did not find an effect of the number of syllables of the production for F0 range, thus showing that the range is independent from the length of the production. But these studies concerned the number of syllables of utterances, not developmentally different productions. Rothgänger (2003) explored the prosodic development of babbling comparing it with the development of cry instead of other non-distress productions, so information about eventual differences among the productions is lacking. Other studies confirmed the necessity to consider the different productions separately, showing differences in the developmental trajectories of the prosodic features of vocalizations and syllabic utterances (Hsu et al., 2000) and different multiword combinations (Behrens & Gut, 2005). These results are vague and confirm that a more detailed description of the phenomena is needed.\n\nSome authors have hypothesized the existence of linguistic trade-offs during development, so that the increased demands in one component of language, such as syntax, may potentially cause a decreased performance in a second component, such as phonology (Crystal, 1978). Furthermore, the interrelationships among different components of language may vary depending on how recently a specific linguistic structure has been learned (Crystal, 1978; Masterson & Kamhi, 1992; Zanchi et al., 2016a). We believe that at early ages this effect may also manifest in relation to the different pre-lexical productions produced by infants. Therefore, we hypothesize that the pre-lexical productions acquired before, and consequently more practiced at the oral-motor level (Oller et al., 1976; Stoel-Gammon, 2011), may have prosodic features different from the later acquired productions, for whom the infant is not yet fluent.\n\nTo assess this hypothesis, the main aim of the present study is to explore the development of F0 related prosodic features of each type of pre-lexical productions observed. To our knowledge, this is the main factor not dealt with so far. As reported above, only differences among the prosodic development of cry and other non-distress productions (Murry et al., 1983) or among productions with a different number of syllables (Robb et al., 1989) have been analyzed.\n\nThe second aim of the present study is to explore individual variability in prosodic features of speech; then, all the analyses will be run with the use of multi-level analysis with the children as the second level.\n\nWe expected to find:\n\n• Different trajectories of the prosodic features of each kind of production considered, with the productions earlier acquired showing different prosodic features than productions later acquired.\n\n• Significant individual variability among children.\n\n\nMethods\n\nFifteen infants (3 females) participated in the study. The sample was not gender-balanced. However, previous studies showed that gender differences in the prosodic aspects of language are present only from late puberty (Bennett, 1983; Fox, 1990; Lee et al., 1999).\n\nAll infants were healthy and full term born. Families were monolingual Italian-speaking, and mothers’ mean age was about 35 years (range: 28 – 42). 60% of them completed high school education, and 40% had a university degree.\n\nMothers were contacted after infant birth, and the first meeting was arranged at the beginning of the 4th month (M age = 4 months, 2 days; SD = 0:05). This age was chosen because around 4-6 months significant changes in the anatomical-physiological structure of the infant’s vocal tract occur, strongly increasing the control of speech articulation with enhanced production of speech-like sounds (Kent, 1976).\n\nInfants were followed from the 4th to the 16th month of age. From the 4th to the 14th month a researcher visited the infant and the mother at home every 15 days (twice a month); after the 14th-month visits were monthly. See Table 2 for a summary of the sessions recorded for each participant. Some infants missed part of the sessions, and not all infants were followed up to the 16th month, since mothers interrupted their participation in the study for personal reasons. Mother and infant were audio-video-recorded during free-play face to face interaction without toys. The mothers were asked to play as they normally did. In total, 295 sessions (M per subject = 20, SD = 5) of about 10 minutes each (M = 10.06 minutes, SD = 1.99) were collected.\n\nThe audio of all the recorded sessions was obtained using the program Audacity Team (available for download at https://www.audacityteam.org/), and all the audible pre-lexical infant productions that did not overlap with other sounds and were noise-free were coded. In line with previous studies, vegetative sounds (such as wheezes, sneezes, coughs, hiccups, and clicking sounds), stress vocalizations (such as whimpering, fusses, and cries), laughs, words and onomatopoeias were not considered (Fasolo et al., 2010).\n\nInfants’ vocal productions (Stark et al., 1993) were coded as:\n\n• Communicative grunt (g): vocalization constituted by a consonant-like sound (e.g., [m]);\n\n• Vocalic sound (v): vocalization constituted by vowel-like sounds (e.g., [a]);\n\n• Simple babbling (cv): vocalizations containing almost one full vowel-like element and one consonant-like element with rapid transition between consonant and vowel (e.g. [ba]);\n\n• Reduplicated babbling (cvcv): vocalization containing rapid repetition of the same sequence of one full vowel-like element and one consonant-like element (e.g., [baba], [tata]);\n\n• Variegated babbling (c1vc2v or cv1cv2): vocalization containing rapid repetition of different sequences; vocalizations comprising at least one full vowel-like element and at least two different consonant-like elements (e.g., [bata]), or two different full vowel-like elements and one consonant-like element (e.g., [beba]).\n\nIn total 9737 productions were coded (M per session = 33, SD = 23.38; M for infant = 645, SD = 329.40).\n\nIn all the tables and figures of the present paper the pre-linguistic productions will be indicated as follows: Grunt = Communicative grunts, Voc = Vocalizations, Babb1 = Simple babbling, Babb2 = Reduplicate babbling, Babb 3 = Variate babbling. Table 2 summarizes the total productions for each subject at each age.\n\nThe PRAAT speech analysis software package (Paul Boersma and David Weenink, Institute of Phonetic Sciences, University of Amsterdam, The Netherlands; Boersma & Weenink, 2005) was used to obtain the prosodic characteristics of each vocal production using the visual inspection of the sound wave represented in the spectrogram to identify the beginning and the ending of the production (D’Odorico et al., 2009). The following measures were calculated on every single production:\n\n- Fundamental frequency mean (F0 mean): calculated automatically in Hz by the PRAAT program.\n\n- Maximum and minimum pitch: the highest and lowest F0 values in the vocal production (Cruttenden, 1997), calculated in Hz.\n\n- Fundamental frequency range (F0 range): the span of F0 changes over the entire pre-lexical production (in semitones). According to the definition of Snow and Balog (2002), it was calculated as the logarithmic difference between the highest and the lowest F0 values in a production, measured in semitones: [12/log(2)]*[log (maximum F0 - minimum F0)].\n\n- F0 final contour: the last movement of the production intonation profile. Each change of F0 values within the production was classified as having either a rising (F0 final rising contour) or falling (F0 final falling contour) contour if the pitch changed (differences between the minimum and the maximum F0 value) by at least two semitones. If the F0 range of all the production was less than two semitones, the contour was classified as F0 level contour.\n\nThe inter-coder reliability between two trained coders was assessed on 20% of the observation sessions randomly selected from each age point. Cohen’s kappa (K) coefficient was calculated to assess the accuracy of vocal productions coding; the value resulted in.93, which is amply sufficient. Concerning the prosodic variables, there were strong correlations between the coders (Pearson’s r) on the calculations of F0 mean (r = .94), highest pitch (r = .87), and lowest pitch (r = .75). The Cohen’s K coefficient on the classification of edge F0 final contours was.83.\n\nThe fit lines presented in the graph of Figure 1 were computed using a Kernel smoothing method. Specifically, we employed a non-parametric regression technique where the kernel function weights the observations within a neighborhood around each point of interest. The bandwidth was chosen to include 50% of the data points, ensuring a balanced trade-off between bias and variance. This approach, as stated by Wand and Jones (1995), and by Wasserman (2006), allowed for flexible modeling of the underlying relationships between variables without assuming a specific parametric form.\n\n\nResults\n\nThe total frequency of each type of vocal production and its percentage on all the productions is given in Table 3.\n\nIn Figure 1 are reported the mean relative frequencies of each type of production aggregated within participants at different ages. The graph shows that vocalizations were over time the most frequent productions with a consistent decrease over the first ten months of life. Grunts were very common during the first seven months of life, but their frequency decreased over time since their use becomes very sporadic. All the three types of babblings started to be present between the 5th and the 6th months, and their use increased over time with a predominance of canonical babbling all over the age period considered.\n\nTo explore the presence of between-subjects variability, a linear regression was conducted with age, age squared, and infants (indicators) as predictors on the dependent variable F0 mean. The results were statistically significant, R2 = .102, indicating that infants and age have an effect on the F0 mean. Coefficients reported in Table 4 show that infants had significantly different coefficients. This confirms the presence of differences among the infants and that these differences should be taken into consideration.\n\nThere are indeed some strong arguments to use multilevel techniques in the analysis of pitch. In this view the infants form a random factor (level 2) and each set of observations (level 1) is nested within each child. All multilevel models were tested with MLwiN 2.33 (Rasbash et al., 2005).\n\nDifferent multilevel models were investigated. The basic model, the unconditional model with no predictors included in the equation (M0 in Table 5), indicated a significant inter-subject variability in the F0 mean (see Table 5); this represents a reason to carry out all the subsequent analyses with the multilevel software. The F0 mean value across subjects and across time was 366 Hz (Table 5), and it is in line with previous studies (see, for example, Amano et al., 2006).\n\nWe also tested further models (M1, M2 and M3) including the effects of age, linear and squared, as fixed predictors (M1), and the fixed effects of type of production variables (M2) and finally a model including also the fixed effects of interactions between age (linear) and each type of production (M3).\n\nWe also tested the models with age as a random factor, the -2LL did not decrease significantly, so there was no reason to treat it as a random factor, we kept age and age squared as fixed factors for all the following analyses. The type of production was treated as a fixed factor with a fixed coefficient and vocalization as the reference category. All the models for F0 mean are therefore random intercept models because no other variable than the children have random effect.\n\nThe equation representing the final M3 was the following:\n\nWhere β0ij=β0+u0j+e0ij and cost = 1\n\nThe same analyses were followed both for F0 mean, for F0 range and F0 final contours using the same schema and the same hierarchical models.\n\nThe first analyses explored the changes in the F0 mean values over time and among the different type of productions. As reported above the basic model (M0) showed there was variation among infants (random part); consequently, all the models included this variation among infants.\n\nWe added age1, linear and squared, as fixed predictors (M1). As can be seen in Table 5, only age linear fixed effects were significant. F0 mean values tended to increase over time.\n\nModel 2 (M2) added to M1 the type of production as a fixed predictor with vocalization as the reference category. Results confirmed the significant effect of age and showed that grunts have the lower mean F0 values, higher values are present for variate babblings, while vocalizations, simple and reduplicate babblings have similar values and are situated at an intermediate level. The lack of differences between mono and by-syllables (simple and reduplicated babblings) was also found by Robb et al. (1989).\n\nModel 3 (M3) added the interaction term between age and type of productions to M2. The effect of age, age squared, and the interaction between reduplicated babblings and age were significant. Nonetheless, the LL did not improve significantly, so Model 3 cannot be considered the best representation of F0 mean development and Model 2 was chosen and represented in Figure 2. Figure 2 shows the distances between the curves, the differences between the intercepts of each production. The form of the curve is due to the introduction of age and age squared in the model.\n\nThe second set of analyses dealt with the changes of F0 range, measured in semitones, over time and among the type of productions (see Table 6). The basic model (M0) gives 4.47 semitone as mean value of the F0 range and shows the significant variation among subjects and over time.\n\nIn Model 1 (M1), the significant effect of age showed that F0 range increased over time. The addition of the type of production, again with vocalization as the reference category, in Model 2 (M2), showed a significant effect of age, age squared and of each type of production except reduplicate babbling. Generally, the effect of age squared showed that F0 range very slightly increased during the first months but decreased later. More complex productions such as reduplicate and variate babblings tend to be produced on average with a wider F0 range than vocalizations. Grunts are the productions with the smallest F0 range. Also, simple babblings showed a narrower F0 range than vocalizations. The difference between simple and reduplicate babblings is in contrast with Robb et al. (1989), who reported monosyllables with a slightly higher F0 range than bi-syllables.\n\nThe inclusion of the interaction term in Model 3 (M3) revealed a significant effect of the interaction between age and variate babblings, but the improvement in LL was very little, so Model 2 was chosen as the best representation of F0 range development. Model 2 is represented in Figure 3.\n\nTo explore the development trajectories of the ability of children to give to F0 changes special directions, multilevel logistic analyses were run using as dependent variable the presence or not of level, rising and falling F0 final contours in the production. Analyses were done on 9597 productions, excluding the productions for which the coding of F0 final contour was unclear due to the spectrogram being too noisy because of interferences or artifacts.\n\nFirstly, Model 0 showed a significant variability between subjects in the production of level contours with an average probability of 79% to produce level contours (see Table 7). The addition of the fixed effects of age and age squared in Model 1 did not show significant effects. Model 2 showed significant effects of reduplicate and variate babblings that are produced at a greater extent with level F0 contours. The probability to produce level productions did not vary over time. The interaction between age and type of production in Model 3 was not significant. Model 2 was chosen as the best representation of the presence of level F0 contours productions, and it is represented in Figure 4.\n\nLogistic Binomial Multilevel results.\n\nConcerning rising F0 final contours, Model 0 indicated significant variations among subjects and a probability of 59% to produced rising contours within the production (see Table 8). Adding age and age squared in Model 1 did not reveal any significant effects. Model 2 showed a significant effect of grunts, reduplicated and variated babblings. Children use less often rising final contours when pronouncing grunts and more often when pronouncing these more complex babblings. The probability to produce rising F0 final contours did not change over time. Model 3 did not reveal any significant effect of interactions. Hence Model 2 was chosen and represented in Figure 5.\n\nLogistic Binomial Multilevel results.\n\nThe same analyses were run for the dependent variable presence or not of a falling F0 final contour (see Table 9). The basic model showed a significant variability among subjects and a general probability of 62% to produce falling final contours within the vocal production. Model 1 showed a significant effect of age squared. The presence of falling final contours is quite stable all over the period considered. In Model 2, the effects of grunts, reduplicate and variate babbling were significant (see Figure 6). Reduplicate and variate babbling were pronounced with higher probability with F0 falling final contours. Model 3 did not reveal any significant effect of the interactions of age and type of production on the presence (or not) of an F0 falling final contour.\n\nLogistic Binomial Multilevel results.\n\n\nDiscussion\n\nTo give a contribution to the contrasting literature on the topic and to supply to the several limitations of previous studies, the present study had the aim to describe the development of F0-related prosodic features of the pre-lexical productions of Italian infants from the 4th to the 16th month of life.\n\nOne of the main findings that emerged is the presence of a significant variability among children. Since in the first months of life children show differences in the use of the voice, not only at the mean fundamental frequency level but in all the examined variables, that can be attributed to physiological differences in the shape and development of the larynx. This finding enchanted the need to put attention to a greater extent on individual variability when studies on infants and children are developed. For example, the F0 mean of children across ages varies between 309 to 392 Hz that indicates a difference of more than four semitones among children. This great individual variability may explain the different values found by previous studies, conducted on small groups of participants. Moreover, the tendency not to consider and control this variability in the analysis may explain the previous confusing or not significant findings. The variability among our 15 children is wider than the range found by Laufer and Horii (1977) within their four children (317 to 342 Hz), and it is in contrast with Flax et al. (1991), who did not find significant differences among their three children. We may suppose that a bigger sample could give a better picture of this variability and it may increase the chance to find such phenomena and therefore to control it. A further longitudinal investigation of these differences at older ages would help understanding if this variability is only present at this stage of physiological organization of the vocal tract or it states later or, eventually, it increases over age to make the well-known differences between the tone of the voice of the different persons.\n\nControlling for this variability, we were able to describe with more accuracy the developmental trajectories for all the variables examined. F0 mean tends to increase over time, about 3.2 Hz per month. This slight increase is in contrast with other previous studies but may confirm the slight increase found in studies with a lower number of subjects as in Laufer and Horii (1977), who found a similar, but not statistically significant, variation. Other authors reported an increase in F0 mean values, however only since the 5th (Fairbanks, 1942) or the 10th month (Murry et al., 1983).\n\nIn the first two years of life, infants improve their interactive abilities as can be seen by the greater duration of gazes and amount of gestures directed to the mother (Papaeliou & Trevarthen, 2006; Trevarthen, 1977). Accordingly, we may hypothesize that the voice is more and more used to establish contact with the caregiver and to respond to stimulation received. It could be possible that to this greater participation to the interaction corresponds an increase in activation state and, therefore, an increase of F0 mean values. Moreover, previous authors evidenced that communicative, investigative or emotional pre-lexical productions show different prosodic features. Specifically, a reduced F0 mean is present in not-communicative productions pronounced, for example, while exploring an object. In contrast, productions directed to the adult during face to face interactions and also productions associated with imperative gestures are pronounced with higher F0 mean (Aureli et al., 2017; Papaeliou et al., 2002; Papaeliou & Trevarthen, 2006). Since we recorded mother-infant interactions during face-to-face interactions without objects we may suppose that the coded infants’ vocal productions were mostly pronounced with the aim to communicate with the mother, so, with a higher F0 mean.\n\nA different result was found concerning the developing trajectories of F0 range. Infants tend to slightly increase the amplitude of the variations within their productions during the first months while after the 7th month the F0 range of all the productions decreases of about one semitone every two months. This may mean that very young infants’ productions are less controlled and characterized by very high variations; after the second half of the first year of life, infants tend to control better their voice and to use prosodic variations that are more similar to adult vocal productions. As previous studies have found infants tend to imitate the variations of the vocal productions of mothers (see Gratier & Devouche, 2011, and Ko et al., 2016) and we may suppose that this ability becomes more efficient after the 7th month. The wider F0 range during the first months of life is consistent with Amano et al. (2006) findings on prosodic development of three Japanese infants. However, these authors reported the decrease in F0 range only after the two-words period. On the contrary, Snow (2004) reported an increase in F0 range from the first to the 4th year of age. The different age ranges considered make it very difficult to compare the findings. We may suppose that our analyses, focused in a shorter age range and with more time points, were more effective in evidencing the variation not reported by other authors.\n\nConcerning F0 contours, most of the vocal productions of infants can be considered flat. This finding is different from previous studies and it may be linked to the fact that during face-to-face interaction infants are not required to produce higher in F0 range productions to, for example, attract mother’s attention, or to ask for an object (see Aureli et al., 2017; D’Odorico & Franco, 1991 and Esteve-Gibert & Prieto, 2013). A further coding of the communicative function of the production would have given more information on this regard. Similarly, the percentages of rising and falling final contours do not vary over age. Our findings are not consistent neither with Snow (2006), neither with the hypothesis of Lieberman (1967). The significant effect of production at every age may contrast the idea that, during the first months of life, prosody is prevalently physiologically controlled. It is clear by our results that from the beginning of pre-lexical speech infants can use their prosodic competences, as confirmed by previous studies evidencing that infants can differentiate accents to signal communicative intent (Prieto et al., 2012).\n\nOur data collection did not last enough longer to test Snow’s hypothesis (2006). Both the probability of producing rising and falling final contours slightly decreases over time, but we did not find the U shape effect found by Snow. If this is simply due to the age range explored in our study, we may suppose that the probability to produce these final contours may increase again later, after the 16th month of life.\n\nThe main finding of the present study is the significant effect of the type of vocal production all over the prosodic variables examined. The effect indicates that all the productions considered show different prosodic characteristics, and these differences lasts all over the age range considered.\n\nGrunts are confirmed to be the less communicative productions, indeed they are pronounced with the lowest F0 mean and F0 range values compared to other productions. Moreover, it’s when pronouncing grunts and vocalizations that infants seem to be less able to use rising and falling final contours. These productions are the most frequent all over the age period considered but resulted to have less communicative intonation features. High F0 mean, wide F0 range and also rising and falling contours may represent an index of activation and excitement, and our results show these prosodic features are more frequent in the productions that are used with a more specific communicative meaning, as the simple and variate babblings (Fasolo et al., 2008).\n\nSome limits of the present study have to be addressed. First, we used as a measure of F0 range the semitones while many previous studies use the F0 mean SD; this makes the results less comparable. Moreover, we did not consider the different communicative intentions of vocal productions (e.g., were they in respond to maternal speech, were they produced to engage maternal attention, to complain about a need, etc.). This should be another important variable that needs to be taken into consideration.\n\nThe present study illustrates the growing need to take into consideration individual variability in assessing infant and children prosody. These findings suggest that in the second half of the first year of life, infants show an intonational repertoire that may contribute to regulating interaction with their partner, which is considered one of the major prerequisites for language acquisition (Papaeliou et al., 2002). The use of multilevel models was very useful to this attend. Applying statistical analyses that are able to explore and control individual variability becomes even more essential when studying children development. Further longitudinal studies may explore if this variability among children is stable over time or it decreases/increases. This would allow to know at what ages is better to control it or not.\n\nAnother implication concerns the need to explore linguistic and prosodic development even at the pre-linguistic stage. The prosody of speech has to be studied considering the type of production analyzed. This, with the code of the communicative intention of the production, will give a very interesting contribution to the study of infants’ prosodic development.\n\nThe study was approved by the ethical committee of the Department of Neuroscience Imaging and Clinical Science of the University of Chieti-Pescara (Ethical approval number: DNISC2962, 06.11.2019) and was conducted according to the American Psychological Association guidelines in accordance with the 1964 Helsinki Declaration.\n\nA written informed consent (approved by the ethical committee) for participation in the study has been obtained by the mothers.",
"appendix": "Data availability statement\n\nOpen Science Framework (OSF): The developing of prosody in infants: a longitudinal study over the first 16 months of life. https://doi.org/10.17605/OSF.IO/7PBN6 (D’Aloia, 2024).\n\nThe project contains the following underlying data:\n\n• Number of prelexical production by child and session.xlsx. Data file which includes the children’s data.\n\n• Read.me.pdf. A checklist adhering to STROBE guidelines for reporting observational studies.\n\nData are available under the terms of Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\nThe extended data for this study is available in the Open Science Framework repository. This extended data is a component of the main project titled “The developing of prosody in infants: a longitudinal study over the 16 months of life.”\n\nOpen Science Framework (OSF). Extended data for “The developing of prosody in infants: a longitudinal study over the 16 months of life.”. Doi: https://doi.org/10.17605/OSF.IO/738W2\n\nThe component contains the following extended data:\n\n• Table 1. Extended data. Data file which includes a literature review on F0 related (F0 mean, F0 range, F0 final contours) prosodic development.\n\nData are available under the terms of Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nAmano S, Nakatani T, Kondo T: Fundamental frequency of infants’ and parents’ utterances in longitudinal recordings. J. Acoust. Soc. Am. 2006; 119(3): 1636–1647. PubMed Abstract | Publisher Full Text\n\nAstruc L, Payne E, Post B, et al.: Tonal targets in early child English, Spanish, and Catalan. Lang. Speech. 2013; 56(2): 229–253. PubMed Abstract | Publisher Full Text\n\nAureli T, Spinelli M, Fasolo M, et al.: The pointing–vocal coupling progression in the first half of the second year of life. Infancy. 2017; 22(6): 801–818. 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PubMed Abstract | Publisher Full Text\n\nPapoušek M, Papoušek H: Forms and functions of vocal matching in interactions between mothers and their precanonical infants. First Lang. 1989; 9(6): 137–157. Publisher Full Text\n\nPrieto P, Estrella A, Thorson J, et al.: Is prosodic development correlated with grammatical and lexical development? Evidence from emerging intonation in Catalan and Spanish. J. Child Lang. 2012; 39(2): 221–257. PubMed Abstract | Publisher Full Text\n\nPrieto P, Vanrell M d M: Early intonational development in Catalan. Paper presented at the Proceedings of the XVIth International Congress of Phonetic Sciences. 2007.\n\nRasbash J, Steele F, Browne W, et al.: A user’s guide to MLwiN Version 2.0. Bristol: Centre for multilevel modelling, University of Bristol; 2005.\n\nRobb MP, Saxman JH: Developmental Trends in Vocal Fundamental Frequency of Young Children. J. Speech Lang. Hear. Res. 1985; 28(3): 421–427. PubMed Abstract | Publisher Full Text\n\nRobb MP, Saxman JH, Grant AA: Vocal fundamental frequency characteristics during the first two years of life. J. Acoust. Soc. Am. 1989; 85(4): 1708–1717. PubMed Abstract | Publisher Full Text\n\nRothgänger H: Analysis of the sounds of the child in the first year of age and a comparison to the language. Early Hum. Dev. 2003; 75(1–2): 55–69. PubMed Abstract | Publisher Full Text\n\nSnow D: Falling intonation in the one- and two-syllable utterances of infants and preschoolers. J. Phon. 2004; 32(3): 373–393. Publisher Full Text\n\nSnow D: Regression and Reorganization of Intonation Between 6 and 23 Months. Child Dev. 2006; 77(2): 281–296. PubMed Abstract | Publisher Full Text\n\nSnow D, Balog HL: Do children produce the melody before the words? A review of developmental intonation research. Lingua. 2002; 112(12): 1025–1058. Publisher Full Text\n\nSnow D, Ertmer DJ: Children’s development of intonation during the first year of cochlear implant experience. Clin. Linguist. Phon. 2012; 26(1): 51–70. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSorianello P: Prosodia: Modelli e ricerca empirica. Carocci; 2021.\n\nSoderstrom M, Blossom M, Foygel R, et al.: Acoustical cues and grammatical units in speech to two preverbal infants. J. Child Lang. 2008; 35(4): 869–902. PubMed Abstract | Publisher Full Text\n\nSpinelli M, Fasolo M, Mesman J: Does prosody make the difference? A meta-analysis on relations between prosodic aspects of infant-directed speech and infant outcomes. Dev. Rev. 2017; 44: 1–18. Publisher Full Text\n\nStark RE, Bernstein LE, Demorest ME: Vocal communication in the first 18 months of life. J. Speech Lang. Hear. Res. 1993; 36(3): 548–558. PubMed Abstract | Publisher Full Text\n\nStoel-Gammon C: Relationships between lexical and phonological development in young children. J. 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Svilupp. 2016a; 20(1): 103–123.\n\nZanchi P, Zampini L, Fasolo M, et al.: Syntax and prosody in narratives: A study of preschool children. First Lang. 2016b; 36(2): 124–139.\n\n\nFootnotes\n\n1 Age squared was divided by 26 (the number of sessions) to make values comparable."
}
|
[
{
"id": "318803",
"date": "01 Oct 2024",
"name": "Sonia Frota",
"expertise": [
"Reviewer Expertise Experimental linguistics and psycholinguistics",
"prosody",
"early language 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\nThis study examined the development fo F0 related variables in Italian-learning infants from 4 to 16 months of age. It certainly addresses a relevant topic, offering additional evidence and a contribution to the scarce literature on early prosodic development. However, the paper requires major revisions before it can be indexed. There are also issues related to the use of the English language that need to be amended. I encourage the authors to address all the major and minor issues detailed below and in the annotated pdf. I hope that the detailed comments provided will be helpful to improve the paper.\nAbstract The presentation of the results is too vague.\nIntroduction\n2nd paragraph: You might want to add European Portuguese to the set of languages studied. The study below includes a comparison with the results reported by Whalen et al., 1991):\nFrota & Vigário (1995) The intonation of one European Portuguese Infant: a first approach. In I. H. Faria & M. J. Freitas (eds) Studies on the Acquisition of Portuguese. Lisboa: Colibri, pp. 17-34.\n3rd paragraph: I believe that you mean in Italian-learning infants. If not, there certainly are studies on infants learning other languages. For example, there is an old study by Shepard and Lane (https://doi.org/10.1044/jshr.1101.94), the study by Mampe et al. (2009), and other work is mentioned in Frota et al., (2016) (such us by Halle et al, or Snow).\np.4 parag. 2: Frota et al. (2016) report development in F0 scaling (which is related to F0 range), which only becomes adult-like around 20-22 months of age. p. 4 parag. 3: I believe that what is relevant is the language infants are exposed to and not the country where the study is conducted. I suggest rephrasing.\nBeyond English-learning infants, Frota & Vigario (1995) found that falling contours predominate in Portuguese-learning infants, who in this respect are similar to English than to French-learning infants. I would suggest reporting here the finding by Whalen et al. (1991) who report that rising contours predominate in French-learning infants. The present study\nparagraph 1: Other studies have suggested that the prosodic component of language shows better performance earlier in development than, for example, other aspects of phonology, or the syntactic component (Prieto et al., 2012; Frota et al., 2016).\nHow are 'early' and 'later' defined? It would be good to give the reader a better understanding of the hypothesis put forward.\nparagraph 2: Please note that there are studies that differentiated babbling from other types of utterances.\nparagraph 4: You expect to find 'significant variability among children'. Why? It would be nice to motivate this expectation.\nMethods Participants If the aspects at stake were not yet analyzed in previous studies, one should not dismiss the possibility of gender differences. Several studies have shown that boys show a slower maturational course of speech motor development. It is thus possible that this might affect prosodic development. Please provide details on how being 'healthy' was assessed.\nProcedure Please provide information on how the families/babies were recruited. Kindly, also refer here to the ethics procedures followed (e.g., submission to ethics committee, prior informed consent, etc.).\nDid all the mothers normally play without toys with their infants? Coding: pre-lexical productions Although the goal is to focus on pre-lexical production, it would be highly informative to know per child how many 'words' were produced and from what age. If a given child at a given point in development is producing a fair amount of words, then perhaps the so-called pre-lexical productions from the same child should be discarded, or at least treated differently from those pre-lexical productions that precede the production of words. Of course, a definition of what counts as a 'word' is needed.\nReliability I'm afraid a clarification is needed. Was mean F0 not automatically calculated as stated above? How could inter-coder reliability be computed for this variable? A note on the availability of the data: The raw data is not available, I believe. This would be important not only to replicate the current analyses, but also to explore the data with new analyses.\nResults Descriptive analysis Does canonical babbling refer to simple babbling? Please keep the terminology the same throughout the paper.\nBetween subjects variability exploration I believe there should instead be a section on the statistical analyses. Maybe I'm missing something. Shouldn't age be factored out to investigated between-subject variability? Also, what is the impact of the different types of productions on such variability? I suggest reorganizing this section so that these issues are immediately put forward, instead of looking at variability per se (as this is naturally a given). Could you provide the measures of comparison among models? For example, did you use Akaike Information Criteria? If not, why not and what were the measures used?\nDiscussion Please rephrase the first sentence, as the use of English needs to be corrected. p. 16, parag.2, lines 6-7: The previous sentence focused on variability across ages. Variability across ages is not individual variability, but variability due to age. One would have individual variability if, for example, different individuals would not show the same trend in variability across age, or the same trend in variability across type of production. The use of 'individual variability' and all the discussion around it, requires clarification and amendment. p. 17, parag.1: To the extent that F0 range is related to scaling of F0 contours, the use of different types of contours would have a tremendous impact on a rough measure such as mean F0 range. Frota et al. (2016), analyzing the F0 contours produced by children, found that F0 scaling is nearly adult-like between 18 and 24 months, depending on the type of F0 contour (with falling contours for statements getting adult-like early than calling contours, for example). p. 17, parag.2: In your data, most of the productions were flat. Could this not be related to the fact that only pre-lexical productions were considered? For example, Prieto et al. (2012) and Frota et al. (2016) considered meaningful utterances according to the criteria proposed in Snow (2006) and found very different results, with falling nuclear contours predominating initially and an increasing diversity of nuclear contours emerging over time (that is already seen between 12 and 16 months, although it becomes most evident from 16 months onwards). p. 17 parag.2: Kindly rephrase the last two sentences. p. 17, parag.5: 'Grunts are confirmed to be the less communicative productions'. Please add a reference here. p. 17, parag.6: Together with the communicative intention, an important limitation is the consideration of general acoustic measures of the productions (along the lines of contour-based approaches) without a look into the structural properties of the melodies produced ( such as type of nuclear contour, i.e., pitch accent and boundary tone).\nPlease rephrase the text within parentheses. Implications for future studies It is difficult to see how the findings from the present study show the presence of an intonational repertoire. What are the structural entities of that repertoire and what do they convey? Please also see the comments 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? 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": []
}
] | 1
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https://f1000research.com/articles/13-896
|
https://f1000research.com/articles/12-1403/v1
|
24 Oct 23
|
{
"type": "Research Article",
"title": "Comparative analysis of psychological well-being and emotional education in graduate students",
"authors": [
"Jenniffer Sobeida Moreira-Choez",
"Tibisay Milene Lamus de Rodríguez",
"Eduardo Javier Espinoza-Solís",
"Graciela Josefina Castro-Castillo",
"Tibisay Milene Lamus de Rodríguez",
"Eduardo Javier Espinoza-Solís",
"Graciela Josefina Castro-Castillo"
],
"abstract": "Background: The growing importance of emotional intelligence in academic and professional contexts has generated a need to explore its linkage with psychological well-being. Furthermore, understanding how various demographic and academic factors can influence students' emotional perception and management is crucial for optimizing educational and intervention strategies. In this context, the primary purpose of this study was to analyze the existing relationship between emotional education and psychological well-being in graduate students.\nMethods: The objective was to conduct a comparative analysis of perceived emotional intelligence (PEI) in different study programs offered at a specific university. The methodology, framed within a positivist paradigm, was based on a quantitative approach and examines the responses of 1,522 university students using the Trait Meta-Mood Scale (TMMS-24).\nResults: This tool, which is divided into three dimensions (emotional attention, emotional clarity, and emotional repair), was analyzed using descriptive statistics, correlation analysis, and ANOVA tests to determine demographic and academic influences on the scores. The findings indicate deficiencies in the areas of Emotional Attention and Emotional Repair, contrasting with a marked prevalence in Emotional Clarity. Variables such as sex, age, and field of study demonstrated an influence on the dimensions of PEI. Notably, significant differences in emotional perception were found between sex and academic fields.\nConclusions: Specifically, training directed towards empathy proved to be a prominent factor in the perception of emotional competencies. This study highlights the influence of demographic and academic variables on emotional competencies, underscoring the need to adapt strategies in education and therapy.",
"keywords": [
"Emotional intelligence",
"psychological well-being",
"emotional education",
"educational strategies",
"graduate students"
],
"content": "Introduction\n\nIn recent years, emotional education has garnered considerable attention across various societal sectors. Zhang and Adegbola (2022) define emotional education as the capability to identify, comprehend, and manage one’s and others’ emotions, a fundamental skill for the holistic development of individuals. It fosters healthy interpersonal relationships and effective handling of intricate emotional situations.\n\nDespite the escalating focus on emotional education, noteworthy gaps exist in contemporary research, particularly regarding its implication for graduate students. Recognizing its pivotal role in their academic journey, there is an imperative need for an enriched understanding of its influence on their psychological well-being and academic outcomes. For graduate students, the stakes are higher, given the demanding and intricate nature of their academic pursuits. Drigas and Papoutsi (2018) postulated that emotional education is crucial for cultivating essential social, cognitive, and emotional competencies, thereby becoming an integral component for the holistic development and thorough preparation of graduate students.\n\nExisting research has yet to fully explore the interplay between emotional education and the psychological well-being of graduate students. A knowledge void persists regarding the impact of emotional education on managing stress, anxiety, and the unique emotional challenges encountered by this demographic. A nuanced exploration of how training in emotional education fosters the development of pertinent emotional and social skills, crucial for their academic and professional trajectories, is warranted.\n\nFurthermore, emotional education is instrumental in enhancing the emotional well-being and mental health of graduate students. Housman (2017) contends that it is integral for honing emotional self-regulation skills, thereby positively influencing emotional well-being and mental health. In a strenuous academic milieu, proficiency in emotional education can equip graduate students with the tools to adeptly navigate negative emotions and cultivate resilience.\n\nAddressing the research deficit in this domain underscores the necessity of a study exploring the correlation between emotional education and psychological well-being among graduate students. This exploration is pivotal for identifying and addressing the lacunae in the emotional education provided and for discerning avenues for enhancement in the graduate programs at Milagro State University. The study aims to pinpoint specific facets of emotional well-being and education requiring refinement to elevate the educational quality at this institution.\n\nThe impetus for this study stems from the imperative to bridge the research gaps concerning emotional education in graduate students. By delving deeper into the nexus between emotional education and psychological well-being, the study aims to forge robust strategies and programs to bolster student well-being and academic accomplishments.\n\nMoreover, the study holds particular relevance for Milagro State University, aiming to spotlight areas warranting refinement in terms of emotional education within graduate programs. The insights gleaned will be instrumental in shaping the development and rollout of tailored workshops, courses, and initiatives addressing the emotional requisites of graduate students.\n\nIt is anticipated that the study will amplify awareness about the significance of emotional education in the higher education landscape. By underscoring the importance of emotional education for both personal well-being and academic and professional success, the study aspires to advocate for its incorporation into curricula and the professional development of educators and practitioners interacting with graduate students.\n\nIn today's scenario, the recognition of the importance of imparting emotional education to graduate students by Milagro State University is paramount. Accordingly, this research endeavors to scrutinize the relationship between emotional education and psychological well-being among graduate students, conducting a comparative analysis across diverse programs offered by the university. The ultimate objective is to identify the elements of emotional well-being and education that warrant enhancement, thereby optimizing the educational quality provided by the institution.\n\nAdditionally, given the diversity in participants, potential differences in outcomes related to sex may emerge in the study. Sex-specific distinctions in emotional education and psychological well-being could offer valuable insights, adding a nuanced layer to the research findings and contributing to the customization of interventions. By considering sex as a variable, the study aims to enrich the understanding of the interaction between emotional education and psychological well-being in the context of graduate students, thus enabling a more comprehensive and tailored approach to improving emotional education.\n\n\nMethods\n\nThe research presented in this document adheres to the positivist paradigm, which aims to uncover the true nature of reality through a quantitative approach (Sparkes, 1992). This approach is grounded in a deductive and logical framework that allows for numerical measurement of variables and the utilization of descriptive statistics to address the research hypotheses. The unit of analysis comprises 1,522 randomly selected students, who are enrolled in various master's programs at Milagro State University.\n\nTo maintain an inclusive and comprehensive approach, the sex of the participants was defined based on self-identification. Participants were given the opportunity to identify themselves as male, female, or other, thereby recognizing the diversity and spectrum of sex identities. This approach is aligned with contemporary scientific and ethical standards, promoting inclusivity and respecting individual autonomy in self-identification.\n\nFor the collection of the necessary data, the Trait Meta-Mood Scale (TMMS-24) questionnaire, created by Salovey et al. (1995), was administered. This questionnaire consists of 24 items that assess individual differences in the ability to be aware of and regulate one's own emotions. Participants responded to the questionnaire using a 5-point Likert scale, where 1 equates to “Strongly Disagree” and 5 to “Strongly Agree”. It is worth noting that this instrument is open access, and is under a Creative Commons license, guaranteeing its availability and accessibility for future research and studies in the field of emotional regulation.\n\nThe scale is divided into three dimensions: emotional attention, emotional clarity, and emotional repair. In the process of assessing perceived emotional intelligence (PEI), a comprehensive numerical representation of each dimension is generated by aggregating the scores corresponding to each of the items that make up that dimension. The index of perceived emotional intelligence (PEI) is then computed by summing the total scores of the three dimensions, serving as a composite measure encapsulating the individual's perceived emotional capacity.\n\nA reliability analysis is conducted for each dimension to ensure the internal consistency of the scales. Subsequently, descriptive statistics of the scores obtained in each dimension and the PEI were generated, offering a general overview of the data behavior. A correlation analysis was carried out to examine the specific relationships between the scores obtained in the different measurements and the PEI.\n\nLastly, an analysis of variance (ANOVA) was performed to investigate the impact of variables such as sex, age, and field of study on the dimensional scores and the PEI. This analysis aids in discerning if there are significant differences in scores based on these demographic and academic categories, thereby providing valuable insights into the influence of these factors on perceived emotional intelligence. The inclusion of sex as a variable, defined through self-identification, contributes to a nuanced understanding of its role and influence on the outcomes of the study, ensuring a robust and comprehensive exploration of the relationship between emotional education and psychological well-being.\n\nAll participants in this study provided informed consent, in compliance with ethical standards for research involving human subjects. They were assured that their participation was voluntary and that they could withdraw from the study at any time without penalty. Confidentiality was maintained by anonymizing all personal data. The research was approved by the Institutional Review Board (IRB) at Milagro State University, under the approval “Oficio Nro. UNEMI-VICEINVYPOSG-DP-155-2023-OF,” dated February 13, 2023.\n\n\nResults and discussion\n\nThe evaluation of the PEI construct, as measured by the TMMS, is critical for understanding various psychological phenomena. The robustness and validity of such an instrument are therefore essential. First, the reliability of an instrument can be assessed through its internal consistency. When examining the dimensions of the TMMS, it's evident that Cronbach's alpha values are in a satisfactory range. The dimensions of Attention, Clarity, and Repair showed alphas of 0.87, 0.89, and 0.85, respectively. These values not only exceed the conventionally accepted threshold for good internal consistency but also closely resembled those found by Extremera and Fernández-Berrocal (2006). This parallel suggests the replicability and stability of the TMMS structure across different samples.\n\nBased on the thorough analysis delineated in Table 1, a noteworthy trend was discerned in the scores across the dimensions of PEI. The confluence of minimum scores for Attention and Repair aligning with the lower limit of the scale invites multifaceted interpretations. For example, as postulated by Fiske (2018), this pattern could be indicative of a pronounced deficit in these particular emotional competencies among certain individuals, suggesting a reduced propensity to attend to or modulate emotions in challenging contexts.\n\nConversely, the scores in the Clarity dimension do not reach the lower extremity of the scale, intimating that even those with diminished emotional capacities retain some level of insight into their emotions. This finding is congruent with the proposition by Lee et al. (2020), positing that emotional clarity is a rudimentary competency, foundational for everyday functioning.\n\nAnalyzing the mean and dispersion revealed a congruent pattern between Clarity and Repair, inferring a potential interrelation. This correlation supports the theory by Extremera and Fernández-Berrocal (2005), which underscores the necessity of comprehending emotions (Clarity) as a precursor to effective management (Repair). In contrast, the Attention dimension manifested a broader distribution, indicative of the heterogeneity in individuals’ propensity to perceive and acknowledge their emotions, a variability echoed by Mauss and Robinson (2009).\n\nIncorporating sex into the analysis offered an enriched perspective, enabling a nuanced exploration of how sex dimensions might interplay with individuals' emotional competencies. This incorporation is pivotal, shedding light on potential disparities or similarities in emotional intelligence across sex identities, thereby contributing to a more comprehensive understanding of the subject.\n\nThe examination of the interdimensional correlations of PEI unfolded patterns consistent with existing literature on emotional intelligence. The substantial correlation between Clarity and Repair (coefficient of 0.637) underscores the symbiotic relationship between the comprehension and modulation of emotions, aligning with insights from Haver et al. (2021).\n\nConversely, the subdued correlations between Attention and the other two dimensions might suggest that heightened awareness does not invariably lead to enhanced understanding or adept emotional regulation—a notion corroborated by Sekreter (2019).\n\nFinally, the strong correlations across all dimensions with the overarching PEI substantiate the framework posited by Alzoubi and Aziz (2021), affirming the integral role each dimension plays in the holistic ability to perceive, comprehend, and regulate emotions. This implies that each dimension, while pivotal independently, also significantly informs and shapes the comprehensive construct of PEI.\n\nTable 2, detailed below, offers a concise representation of these Pearson correlations between the TMMS dimensions and PEI. Each numerical value in the table reflects the strength and direction of the relationship between the dimensions, providing a solid foundation for deeper interpretations and future research in this area.\n\nWithin the sphere of scientific inquiry, elucidating the potential ramifications of diverse factors on principal variables is paramount. This research embarked on a nuanced exploration of how distinct elements, notably sex, age, and educational attainment, might modulate the dimensions of emotional intelligence—Attention, Clarity, and Repair—and the composite measure of PEI.\n\nThe discernible variance in the relationship between these elements and the PEI dimensions within the context of the TMMS necessitates scrupulous scrutiny. The manifestation of sex, age, and educational attainment as independent variables substantiates the concept that individual and demographic attributes engage in intricate interplays with emotional intelligence, resonating with earlier studies (Deng, 2021; Manca et al., 2019).\n\nIn particular, the significant influence of age and educational attainment on the Attention and Clarity dimensions aligns with the extant literature. The evolution of emotional maturity, concomitant with aging, can potentially enhance the faculties to discern and clarify emotions (Gao et al., 2021; Vaish et al., 2008). Concurrently, educational attainment, emblematic of proficiency and aptitude in a particular field, could furnish a structured paradigm, thereby facilitating the processes of emotional discernment and clarification.\n\nThe integration of sex as a variable in this discourse enriches the analysis, offering a lens through which to examine its interaction with emotional intelligence dimensions. This integration is pivotal as it delves into the nuances of how sex may uniquely contribute to the dynamics of emotional intelligence, thereby augmenting the comprehensiveness of the study.\n\nInterestingly, the singular impact of age on the Repair dimension prompts contemplation, positing that the capability to amend and regulate emotions might be more contingent upon accrued experience and maturity than on elements such as proficiency in a particular domain. This observation presents a divergence from the findings of Herd and Kim-Spoon (2021), who elucidated the progressive enhancement and adaptation of emotional regulation through time and experience.\n\nMoreover, the salience of educational attainment as the sole significant determinant in the overarching measure of PEI underscores the pivotal role of domain-specific competence and expertise in shaping the holistic perception of emotional intelligence. This inference aligns with the conceptualization by Dolev and Leshem (2017), proposing that the manifestation of emotional intelligence in academic and professional realms is predominantly influenced by competence within those domains.\n\nThese results underline the complexity and specificity of the interactions between the dimensions of emotional intelligence and the demographic and academic factors under study. For a more detailed and visual understanding of these findings, Table 3 provides a comprehensive breakdown of the variance analysis performed.\n\nThe multifaceted nature of emotional intelligence, illuminated by a plethora of studies examining it from diversified vantage points, accentuates the imperative of identifying underlying patterns within the amassed data (Azevedo et al., 2013; Gooty et al., 2014). This present investigation meticulously underscores the capacity to extract such nuanced patterns, thereby offering an intricate framework elucidating the interplay between certain demographic, academic factors, and distinctive dimensions of emotional intelligence.\n\nThe study's results, particularly those relating to the “attention” dimension, unveil a noteworthy convergence between students in the 21 to 30 years age bracket and those surpassing 50 years. Such a pattern potentially alludes to the existence of distinct life phases where attentiveness to emotions experiences amplification. Dickerson and Quas (2021) have theorized that emotional awareness might be particularly amplified both in youth—attributed to the transitions and revelations inherent to this life stage—and in older age, characterized by heightened reflection and self-awareness.\n\nDelving into the dimensions of “clarity” and “repair,” the ascension in mean scores concurrent with aging intimates an enhancement associated with accrued life experiences and the refinement of emotional regulation competencies—a proposition corroborated by preceding research (Blasco-Belled et al., 2020; Martínez-Marín et al., 2021). Concurrently, the prominent scores of Early Education students in pivotal dimensions of emotional intelligence may be ascribed to the inherent characteristics of their scholastic curriculum. Education, predominantly at the foundational level, invariably necessitates profound empathy and refined interpersonal acumen (Blakemore and Agllias, 2020). The cultivation and comprehension of emotions, both personal and of others, are indispensable in this field, thereby potentially manifesting in the elevated scores observed among these students.\n\nMoreover, incorporating sex as an analytical variable in this discourse augments the depth of the study, furnishing a nuanced perspective to discern its potential interactions with the facets of emotional intelligence. This inclusion is quintessential, elucidating the intricate ways in which sex may shape and influence the dynamics of emotional intelligence, thereby enriching the holistic understanding of this complex construct. The intersectionality of sex with other demographic and academic variables provides a fertile ground for further exploration, potentially unveiling additional layers of complexity and contributing to a more comprehensive and nuanced appreciation of emotional intelligence in diverse populations.\n\nTable 4 provides a detailed analysis of the interaction between demographic and academic variables with the dimensions of emotional intelligence. Through the DMS Test for mean comparison, significant differences and similarities were determined among the groups. The assigned letters (A, B, C) denote the statistical significance between the means; means with the same letter show no significant differences at the 0.05 level.\n\nA pivotal insight emanating from the conducted analysis pertains to the substantial correlation between emotional clarity and age. The existing corpus of research has consistently underscored the evolution of the capacity to interpret and comprehend emotions, a progression modulated by a confluence of biological underpinnings and accrued socio-emotional learning (Averill, 1980; Mayer et al., 2016). The Chi-squared value of 22.27 manifested in this investigation fortifies this conceptualization, emphasizing that emotional clarity is a dynamic attribute, subject to vicissitudes across the chronological trajectory of an individual's existence.\n\nConcurrently, the discerned disparities in the dimensions of attention and clarity associated with sex, substantiated by Chi-squared values of 53.96 and 18.83, cohere with the existing scholarly discourse. This body of literature posits that variations exist in the ways men and women process and engage with emotions, potentially attributable to a matrix of sociocultural constructs and inherent biological determinants (Averill, 1976; Meyers-Levy and Loken, 2015; Whittle et al., 2017). It is imperative to elucidate that such differences do not insinuate a hierarchical dichotomy or superiority of one over the other; rather, they signify diversification in the modalities of experiencing and conceptualizing emotions.\n\nFurthermore, the discernible association between one's field of mastery and the dimensions of emotional intelligence, corroborated by Chi-squared values of 13.34 and 9.93, intimates the influential role of academic training and experiential learning in sculpting emotional perception and discernment. It emerges as plausible that distinct academic disciplines, by virtue of their inherent characteristics and thematic emphasis, foster competencies germane to emotional recognition and clarity (Chen and Lu, 2022; Denham and Brown, 2010).\n\nFigure 1, presented below, illustrates this interaction. It provides a visual representation of the frequencies of categorized clarity according to different age cohorts. This type of graphical representation allows for a more intuitive interpretation of the data, highlighting trends, consistencies, or possible anomalies among the groups.\n\nThe graphical representation in Figure 1 highlights these temporal dynamics of emotional perception in relation to age. It is revealing to observe that, with advancing age, there is an increase in the “excessive” category. This trend could align with the idea that accumulated experiences and introspection throughout life enrich emotional perception (Bukor, 2015). Older individuals may have a more finely-tuned ability to recognize and understand the depth and complexity of their emotions, resulting in an “excessive” perception of emotional clarity.\n\nIn contrast, the “improve” category exhibits a notable decline with age. This could be interpreted as increased confidence and certainty in emotional perception acquired over the years. The fact that this trend starts high in the youngest group and decreases with age suggests that, over time and experience, there is a consolidation of emotional understanding (Casale et al., 2022).\n\nHowever, while these trends provide a fascinating insight into the evolution of emotional clarity throughout life, it is essential, as in all research, to maintain a critical perspective. Individual differences, cultural factors, socioeconomic factors, and life experiences can modulate these patterns (Gross and John, 1995; Seixas et al., 2021).\n\nNext, Figure 2 is presented, where a visual representation of the frequencies of categorized emotional attention based on sex is displayed. This graph provides a revealing perspective on how sex differences may be associated with variations in attention directed towards emotions.\n\nIn Figure 2, which illustrates the distribution of attention frequencies according to sex, distinctive patterns are observed in relation to the categories of emotional attention, mainly in the “adequate,” “little,” and “much” categories.\n\nThe female sex appears to predominate in the “adequate” and “little” categories, suggesting that females, in this study, tended to report levels of emotional attention that range between moderate and low. On the other hand, in the “much” category, a predominance of the male sex was observed, indicating that men in this sample report a high level of attention towards their own emotions or those of others.\n\nThese observations are consistent with literature in Psychology and Neuroscience that has explored sex differences in emotional perception and regulation. For example, Kashdan et al. (2009) posited that, in general, women may be more attuned to emotions, which could translate into more balanced or “adequate” levels of emotional attention. However, this does not necessarily imply that women pay less attention to emotions than men. Instead, it suggests that women may be more efficient in regulating the amount of attention they give to emotions, avoiding extremes.\n\nOn the other hand, the fact that men stand out in the “much” category could reflect a tendency among some men to be hyper-aware or excessively attentive to certain emotions. This pattern could be related to sociocultural norms that, in many contexts, discourage emotional expression among men, leading them to greater introspection and self-awareness (Dworkin and Weaver, 2021).\n\nHowever, it is crucial not to generalize these findings to all populations or interpret them as reflecting fixed biological differences between sex The observed differences may be influenced by sociocultural, educational factors, and individual life experiences.\n\nIn the following Figure 3, it is illustrated how the frequencies of categorized emotional clarity vary according to sex. This visualization will allow the exploration of whether there are distinctive patterns between sex concerning the clarity of their emotions.\n\nIn the field of emotional intelligence, emotional clarity denotes an individual's ability to identify and understand their own emotions, an aspect that is of great importance as it provides insights into how people process and manage their emotions in daily life. Figure 3 offers a detailed view of the frequencies of categorized emotional clarity according to sex.\n\nAccording to the data presented in Figure 3, it is observed that women tend to report higher frequencies of levels of emotional clarity considered “adequate” or “excessive” compared to men. However, in the “improve” category, men surpass women in frequency, suggesting a greater inclination on their part to feel that they need to improve in this aspect.\n\nThese differences can be interpreted from various perspectives. According to Doherty (1997), women tend to be more introspective and are socially conditioned to be more expressive and aware of their emotions, which could explain the higher frequencies in the “adequate” and “excessive” categories observed in females. In contrast, men, subject to certain sociocultural norms, might feel less encouraged to explore and understand their emotions, which could influence their perception of the need to “improve” in this area.\n\nAdditionally, it is interesting to highlight the hierarchy observed in the frequencies for both categories: “adequate”, “excessive”, and “improve”. These findings underline that, regardless of sex, most individuals feel that they possess an acceptable degree of emotional clarity. However, it is in the “improve” category where the most significant contrast between the sexes is found, prompting reflections on the differences in emotional self-assessment and the potential sociocultural influences underlying this perception.\n\nFinally, it is imperative to emphasize that, while these findings are revealing, they should not be interpreted simplistically. Differences in the self-perception of emotional clarity can be multifactorial and, as suggested by Gomez-Baya et al. (2017), may be influenced by both biological and sociocultural factors. In this context, a detailed understanding of the observed patterns related to emotional clarity and sex opens doors for future research and reflections in the field of Emotional Psychology.\n\nThe following Figure 4 offers a revealing perspective on the interaction between emotional clarity and academic specialization at the Master's level. Through this graphic representation, the aim is to analyze the possible influence of academic training on the perception and understanding of emotions among postgraduate students.\n\nEmotional attention refers to an individual's ability to tune into and be aware of their own emotions as well as those of others. This construct has crucial implications in the academic and professional world, as the way an individual pays attention to emotions can influence their learning and teaching abilities, as well as their capacity to interact with others in educational contexts.\n\nAccording to Figure 4, a notable relationship is evident between attention categories and the type of Master's program students are enrolled in. This relationship provides information on how different specializations may influence students' self-perception of emotional attention.\n\nA key finding observed is the gradient in the “adequate” category. Parada-Cabaleiro et al. (2020) argued that adequate perception of emotions is crucial for effective emotional processing. Students in \"Early Childhood Education,\" who often work with young children, might develop more finely-tuned emotional attention due to the intuitive and non-verbal nature of communication at early ages. This finding is corroborated by results obtained in studies like that of Joss et al. (2020), who argue that working with younger populations can cultivate greater sensitivity and attention to emotions.\n\nOn the other hand, the “low” category suggests a perception of insufficient emotional attention. Here, the highest frequency corresponds to students in the \"Education\" Master's program. According to Jamil et al. (2023), traditional education often prioritizes cognitive skills over emotional skills. However, it is essential to consider that the type of population or educational context these programs target may influence these results.\n\nLastly, the “high” category presents an interesting pattern. The \"Basic Education\" Master's holds the highest point, indicating that these students perceive elevated emotional attention. Aguado et al. (2018) argue that emotional attention can be influenced by the demands of the context. Basic education often requires a greater capacity to tune into a wide range of emotions due to the diversity of ages and issues.\n\nIn Figure 5, the distribution of frequency categories of clarity, which have been crossed with different types of Master's programs, is illustrated. This graphic representation aims to establish a relationship between the perception of clarity and different postgraduate students, allowing for a more detailed evaluation and a deeper interpretation of the collected data.\n\nFigure 5 offers a detailed view of how emotional clarity relates to the academic specialization that students choose at the Master's level. This graphical representation indicates a notable dependency between the perception of emotional clarity and the nature of the academic program being pursued.\n\nAnalysis of the graph reveals that the categories of “adequate” and “excessive” in emotional clarity exhibit a pattern of consecutive increase from students in \"Education\" to those in \"Early Childhood Education\" (\"Ed. Inicial\" in the original text). This finding is consistent with previous research that suggests that certain academic programs, especially those oriented towards initial training in education, may place a stronger emphasis on emotional development (Hodson, 2003; McCoy and Wolf, 2018).\n\nOn the other hand, it is intriguing to note that the “improve” category reflects an inverse trend. Specifically, those students in the \"Education\" Master's program show higher percentages, which could imply a greater awareness of their areas for improvement in emotional understanding or, alternatively, a program that has yet to fully emphasize this domain, as suggested by some authors (Yang et al., 2022).\n\nIt is essential to point out that while these patterns may reflect the influence of curriculum and pedagogy on the perception of emotional clarity, they could also possibly reflect preexisting characteristics of the students who choose these programs. For example, those with intrinsically high emotional clarity may be more attracted to programs like \"Early Childhood Education,\" given their direct and profound interaction with child development (Ryan and Deci, 2020).\n\n\nConclusions\n\nInitiating a study that seeks to decipher the relationship between demographic and emotional variables represents a challenge. However, the results of this research shed light on this complex interaction, with a specific focus on emotional clarity and attention. Based on rigorous quantitative methodology, detailed relationships were discovered that model these emotional capacities in various populations.\n\nThe relationship evidenced between age and emotional clarity is undeniable. As the years pass, lived experiences and maturity have a positive impact on people's interpretation and response to their emotions. This relationship not only reinforces traditional concepts about the wisdom associated with aging but also offers opportunities, especially in tailoring interventions according to age groups for better outcomes.\n\nOn the other hand, when considering gender, differences were found in emotional attention and clarity, which are not only notable but also enlightening. It could be deduced that these differences arise from a combination of factors, from socio-cultural constructs to biological differences. Understanding these variations is essential, and from this perspective, it becomes imperative to reconsider and adapt intervention and education strategies for an equitable approach.\n\nFollowing this line of research, the link between academic training and emotionality also stood out, particularly regarding Master's levels. It was revealed that certain academic specializations play a significant role in the development of people's introspection and emotional awareness. This relationship strengthens the bond between formal education and emotional skills.\n\nIn light of this revelation, it would be appropriate to consider that the adaptation and refinement of specific pedagogical methods could strengthen emotional clarity and attention according to the academic realm. This adaptation in teaching provides a scenario where future professionals could develop with greater emotional acumen and self-awareness.\n\nHowever, it is essential to take into account the practical implications of these findings. It is evident that any educational or therapeutic planning must consider these demographic variables. Ignoring these differences carries the risk of implementing less effective or incorrect interventions.\n\nEmphasizing this aspect, it is essential for professionals in education, therapy, and mental health to be aware of these discoveries. With this information, they can design and apply strategies tailored to individual needs, enhancing their beneficial impact.\n\nAlthough this work contributes to the academic field, it should not be considered as a definitive answer. It should be viewed more as a foundation for future research. The dynamics between demography and emotional skills have multiple facets, and it is likely that many aspects remain to be explored.\n\nFrom this perspective, the study does not end a debate, but invites future research. The questions that arise, particularly regarding how other socio-economic or demographic factors might influence emotional clarity and attention, have great potential. This work aims to encourage future explorations in an area of such relevance and fascination.",
"appendix": "Data availability\n\nFigshare: Data-Comparative Analysis of Psychological Well-being.xlsx. https://doi.org/10.6084/m9.figshare.24148155.v1\n\nThe project contains the following underlying data:\n\n- Data-Comparative Analysis of Psychological Well-being.xlsx\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 would like to thank the Graduate Program of the State University of Milagro, Ecuador.\n\n\nReferences\n\nAguado L, Martínez-García N, Solís-Olce A, et al.: Effects of affective and emotional congruency on facial expression processing under different task demands. Acta Psychol. 2018; 187: 66–76. PubMed Abstract | Publisher Full Text\n\nAlzoubi HM, Aziz R: Does Emotional Intelligence Contribute to Quality of Strategic Decisions? The Mediating Role of Open Innovation. Journal of Open Innovation: Technology, Market, and Complexity. 2021; 7(2): 130. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nJoss D, Lazar SW, Teicher MH: Nonattachment Predicts Empathy, Rejection Sensitivity, and Symptom Reduction After a Mindfulness-Based Intervention Among Young Adults with a History of Childhood Maltreatment. Mindfulness. 2020; 11(4): 975–990. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKashdan TB, Mishra A, Breen WE, et al.: Gender Differences in Gratitude: Examining Appraisals, Narratives, the Willingness to Express Emotions, and Changes in Psychological Needs. J. Pers. 2009; 77(3): 691–730. PubMed Abstract | Publisher Full Text\n\nLee H, Mandalapu V, Kleinsmith A, et al.: Distinguishing Anxiety Subtypes of English Language Learners Towards Augmented Emotional Clarity. Artificial Intelligence in Education. 2020; 157–161. Publisher Full Text\n\nManca F, Sivakumar A, Polak JW: The effect of social influence and social interactions on the adoption of a new technology: The use of bike sharing in a student population. Transportation Research Part C: Emerging Technologies. 2019; 105: 611–625. Publisher Full Text\n\nMartínez-Marín MD, Martínez C, Paterna C: Gendered self-concept and gender as predictors of emotional intelligence: a comparison through of age. Curr. Psychol. 2021; 40(9): 4205–4218. Publisher Full Text\n\nMauss IB, Robinson MD: Measures of emotion: A review. Cognit. Emot. 2009; 23(2): 209–237. Publisher Full Text\n\nMayer JD, Caruso DR, Salovey P: The Ability Model of Emotional Intelligence: Principles and Updates. Emot. Rev. 2016; 8(4): 290–300. Publisher Full Text\n\nMcCoy DC, Wolf S: Changes in classroom quality predict Ghanaian preschoolers’ gains in academic and social-emotional skills. Dev. Psychol. 2018; 54(8): 1582–1599. Publisher Full Text\n\nMeyers-Levy J, Loken B: Revisiting gender differences: What we know and what lies ahead. J. Consum. Psychol. 2015; 25(1): 129–149. Publisher Full Text\n\nParada-Cabaleiro E, Costantini G, Batliner A, et al.: DEMoS: an Italian emotional speech corpus. Lang. Resour. Eval. 2020; 54(2): 341–383. Publisher Full Text\n\nRyan RM, Deci EL: Intrinsic and extrinsic motivation from a self-determination theory perspective: Definitions, theory, practices, and future directions. Contemp. Educ. Psychol. 2020; 61: 101860. Publisher Full Text\n\nSalovey P, Mayer JD, Goldman SL, et al.: Emotional attention, clarity, and repair: Exploring emotional intelligence using the Trait Meta-Mood Scale. Emotion, Disclosure, & Health. 1995; 125–154. Publisher Full Text\n\nSeixas R, Pignault A, Houssemand C: Emotion regulation questionnaire-adapted and individual differences in emotion regulation. Eur. J. Psychol. 2021; 17(1): 70–84. Publisher Full Text\n\nSekreter G: Emotional Intelligence as a Vital Indicator of Teacher Effectiveness. International Journal of Social Sciences & Educational Studies. 2019; 5(3).\n\nSparkes A: Research In Physical Educ. & Sp. Sparkes A, editor. Routledge; 1992. Publisher Full Text\n\nVaish A, Grossmann T, Woodward A: Not all emotions are created equal: The negativity bias in social-emotional development. Psychol. Bull. 2008; 134(3): 383–403. Publisher Full Text\n\nWhittle S, Simmons JG, Allen NB: Emotion and Gender-Specific Neural Processing in Men and Women. Principles of Gender-Specific Medicine. Elsevier; 2017; (pp. 183–201). Publisher Full Text\n\nYang Y, Zhu G, Chan CKK: Evolution of the academic emotions of academically low-achieving students in knowledge building. Int. J. Comput.-Support. Collab. Learn. 2022; 17(4): 539–571. Publisher Full Text\n\nZhang W, Adegbola O: Emotional intelligence and public relations: An empirical review. Public Relat. Rev. 2022; 48(3): 102199. Publisher Full Text"
}
|
[
{
"id": "218147",
"date": "21 Nov 2023",
"name": "Adriana Beatriz Sánchez-Urdaneta",
"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 consider that the bibliography used partially corresponds to the research. Although relevant references on emotional intelligence and psychological well-being are included, there is a need to go deeper into specific studies on emotional education in graduate students, which is what the study refers to. On the other hand, I also consider that some paragraphs need to support the information provided with certain bibliographical references. It is also important to point out that, although a high percentage of the bibliography used is updated in the last 5 years, only one reference corresponding to 2023 is used.\nIt is true that this is a quantitative study with a considerably large sample and validated instruments are used, which is appropriate. However, I believe it is necessary to expand on the details of the sample selection process and the statistical analyses performed. I consider that the methods and analyses are not described in sufficient detail to allow an exact replication of the study.\nIt is also important to note that the authors have followed appropriate guidelines regarding informed consent of the participants and approval by an ethics committee. However, I believe it is unclear whether specific guidelines were followed in the development and reporting of the quantitative research.\nAs for statistical analysis, appropriate tests such as ANOVA, Pearson correlations and descriptive statistics are used. However, more detail is needed on the specific procedures and parameters used in these tests in order to adequately evaluate their implementation. The source data according to the information provided are available, so with the results presented in tables and figures and the data, the reproducibility of the information is feasible. Regarding the conclusions presented, they are partially based on the results, making very general statements about the differences between sex and age that would require a more robust support from the statistical analysis. For example, differences between men and women are mentioned, but no statistical evidence is reported to validate these differences. Nor do they support them through the use of bibliographic references related to this aspect.\nThe discussion acknowledges some limitations regarding the possible influence of cultural factors and individual experiences. However, important limitations such as the cross-sectional design of the study are not discussed.\nIn summary, the study has a solid technical basis, but I consider that it is necessary to deepen the bibliography, to better detail the methods and to strengthen the information generated by the study. On the other hand, the statistical analysis seems appropriate, but lacks detail. The conclusions are not always solidly supported by the results presented. Further discussion of methodological limitations is required. I believe that, with these adjustments, the article could provide interesting results, and the solidity and reproducibility of the article on a relevant topic such as emotional education in graduate students would be improved.\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? Partly",
"responses": [
{
"c_id": "11581",
"date": "06 Aug 2024",
"name": "Jenniffer Sobeida Moreira Choez",
"role": "Author Response",
"response": "Distinguished reviewer, Thank you for your valuable suggestions that have significantly contributed to improving the quality of our article. Below, we describe the changes made in response to your recommendations: In-depth focus on specific studies about emotional education in graduate students: We have enriched the theoretical framework by incorporating current research that directly addresses emotional education in graduate contexts. Recent studies have been added to provide a more solid and contextualized foundation on the relevance of the topic in the current academic landscape. Support with additional bibliographic references: We have enhanced the bibliographic support in key sections of the manuscript by integrating recent and relevant academic sources to strengthen the claims and conclusions derived from our data analysis. This approach ensures that all significant statements are backed by relevant and up-to-date empirical evidence. Details on the sample selection process and statistical analyses: We provided detailed descriptions of the sample design and analytical procedures, including details on the sample size calculations and specific statistical techniques used, such as ANOVA and Pearson correlations. This level of detail is essential to allow for the replication of the study and to enhance methodological transparency. Clarity in ethical guidelines and informed consent: Information on compliance with ethical standards has been expanded, detailing procedures for informed consent and ethical approval of the study, which is crucial to ensure the integrity and ethics of the research process. Robustness of statistical analysis and caution in conclusions: The study's conclusions were revised to reflect a more conservative interpretation based on the data of observed differences by sex and age, highlighting the need for further research to allow a more robust validation of these findings. Discussion on the limitations of the cross-sectional design: A critical discussion on the limitations imposed by the cross-sectional design used has been integrated, emphasizing the importance of future longitudinal studies to confirm and extend the presented findings. These adjustments have been made to ensure that the study not only responds to the specific needs identified by your review but also enhances its contribution to the field of emotional education in graduate contexts. We appreciate your essential input in the review process and hope that the changes made meet the expectations of rigor and clarity required for the publication and indexing of our work."
}
]
},
{
"id": "218145",
"date": "16 May 2024",
"name": "Maira Alejandra Pulgarín Rodríguez",
"expertise": [
"Reviewer Expertise Education process."
],
"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 study conducted by Moreira et al. constitutes an important contribution to the study of sustainability in the context and well-being of students in higher education. The objective of the research, which was to compare the perceived emotional intelligence in different programs, can be clearly identified. Thus, enlightening results were obtained through the application of the quantitative method that sought to examine the responses of 1,522 university students using the Trait Meta-Mood Scale (TMMS-24).\nAlthough carrying out quantitative studies allows to recognize a factual vision of the object of study, it is necessary to make an exhaustive tracking of the same that allows to have a global context of what is analyzed, in that case in the introduction it is required to make an extension in the existing foundations regarding the categories defined for the study, only three referents are located, although it is a novel topic there are different optics that could give a better support for what they present later in the method and the results. Likewise, the conclusions of the study do not have any reference that allows validating or corroborating a previously established theory or if new knowledge would be generated.\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": []
}
] | 1
|
https://f1000research.com/articles/12-1403
|
https://f1000research.com/articles/12-1382/v1
|
20 Oct 23
|
{
"type": "Research Article",
"title": "The impact of energy releasing B-vitamin intake on indices of obesity and cardiac function: a cross-sectional study",
"authors": [
"Lana M. Agraib",
"Islam Al-Shami",
"Buthaina Alkhatib",
"Hanan Hasan",
"Lana M. Agraib",
"Islam Al-Shami",
"Hanan Hasan"
],
"abstract": "Background: B vitamins play a crucial role in the balance and metabolism of energy. Energy metabolism mainly benefits from the B-complex vitamins. Specifically, decarboxylation, transamination, acylation, oxidation, and reduction of substrates that are ultimately employed in energy intake require thiamin, riboflavin, niacin, and vitamin B6. Vitamin deficiency could lead to chronic disease occurrence. Objectives: To assess the impact of energy-releasing B-vitamins intake (B1, B2, B3, and B6) on selected indices of obesity and cardiac function. Methods: A cross-sectional study was performed on 491 apparently healthy adults (18-64 years old) between January and May 2019 at Hashemite University, Jordan. Anthropometric measurements were taken, lipid profiles were analyzed, and indices of obesity and cardiac function were calculated. The typical dietary intake of B1, B2, B3, and B6 vitamins was calculated. Results: Conicity index (CI) and abdominal volume index (AVI) scores significantly decreased with the increased adjusted vitamin B1 and B6 intake. Also, body roundness index (BRI), weight-adjusted-waist index (WWI), lipid accumulation product (LAP), and atherogenic index of plasma (AIP) scores were decreased with the increase of adjusted B6 intake (p<0.05). The total sample showed a significant inverse weak correlation between energy-adjusted intake of B1 and AVI (r= -0.156, p=0.001) and BRI (r= 0.111, p=0.014). Similar correlations were detected among male participants between energy-adjusted B1 intake and BAI, AVI, and BRI. Female participants had a significant weak inverse correlation between BAI and energy-adjusted B2 (r= -0.180, p=0.029) and B6 intake (r= -0.212, p=0.010). Only B1, the vitamin, significantly explained 2.43 and 1.24% of changes observed in the AVI and BRI scores, respectively (p<0.05). Conclusions: Increasing the intake of B1, B2, and B6 may significantly lower indices of both obesity and cardiac function regardless of sex differences. Thus reducing the occurrence of obesity and related coronary heart diseases.",
"keywords": [
"energy-releasing vitamins",
"obesity indices",
"cardiac function indices",
"abdominal volume index",
"body roundness index"
],
"content": "Introduction\n\nMicronutrients work as coenzymes, cocatalysts, and buffers and are essential for various cellular and biochemical processes, such as releasing energy for synthesis, movement, and other processes.1 Due to their impact on intracellular homocysteine concentration and oxidative stress, subclinical deficiencies in several micronutrients have the potential to significantly slow the development of chronic disease.2 When the consumption of a micronutrient falls below the current recommended dietary amount, a significant chronic metabolic disturbance may result from the nutrient deficiencies such as obesity and metabolic syndrome.2,3 In recent years, many studies approved that nutrients could play a vital role in obesity and metabolic syndrome prevention. Also, energy-dense foods with deficit nutrients contribute to the development of obesity, metabolic syndrome, and inflammation.4,5\n\nB vitamins play a crucial role in the balance and metabolism of energy.6 Energy metabolism mainly benefits from the B-complex vitamins. Specifically, decarboxylation, transamination, acylation, oxidation, and reduction of substrates that are ultimately employed in energy intake require thiamin, riboflavin, niacin, and vitamin B6. One or more of these are also necessary for synthesizing steroids, fatty acids, cholesterol, amino acids, and glucose.7 B-vitamin deficiency may impact energy metabolism, and cause insulin resistance, chronic inflammation, obesity, and elevated oxidative stress, which may contribute to the pathophysiology of metabolic syndrome.8,9 B-vitamin deficiency has been approved in individuals with obesity and metabolic syndrome.2,10 Moreover, thiamin (B1) and riboflavin (B2) intake are inversely associated with body mass index (BMI).2,6 As energy metabolism may be affected by deficiencies in biotin, niacin (B3), folate, and vitamins B6 and B12, which may enhance the generation of reactive oxidants and inflammatory reactions, lipogenesis may also be promoted, which may increase obesity.11,12 Additionally, B vitamins play a vital role (methyl group donor and act as a coenzyme) in DNA methylation, which is important for body adiposity regulation13 and is associated with BMI.14\n\nWu et al.,5 suggested that a higher intake of vitamins B1, B2, B3, B6, and dietary folate were associated with a reduced risk of metabolic syndrome. Also, numerous cardiovascular diseases (CVDs), and risk factors, such as type 1 and type 2 diabetes, obesity, chronic vascular inflammation, dyslipidemia, heart failure, myocardial infarction, and depression, have been linked to B1, B3, and B6 deficiency.10,15\n\nDietary intake of B vitamins has been found to be inversely related to CVD, as their attribution in lowering CVD risk factors, such as plasma homocysteine, serum triglycerides, and C-reaction protein.16 These risk factors have been linked to the atherosclerotic process17 and endothelial dysfunction,18 which engage in CVD development. B vitamins play a role in the metabolism of one carbon unit, therefore each of these nutrients may have an impact on the pathological development of CVD by reducing homocysteine concentrations, methylation processes, and oxidative stress.19,20\n\nFurthermore, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are redox mediator coenzymes that are precursors of B3,21 which has also been demonstrated to enhance levels of high-density lipoprotein cholesterol (HDL), lower levels of triglycerides (TG), very low levels of low-density lipoprotein cholesterol (VLDL-C), and dramatically diminish the risk of CVD and the progression of atherosclerosis.22 Based on the aforementioned, not enough data are available to cover the association between energy-releasing vitamins with indices of obesity and cardiac function. So, this study aimed to assess the impact of energy-releasing B-vitamins intake (B1, B2, B3, and B6) on selected indices of obesity and cardiac function.\n\n\nMethods\n\nA cross-sectional study design was used and conducted on 491 apparently healthy randomly selected male and female adults, university employees, aged between 18-64 years old (between January and May 2019) at Hashemite University, Jordan. The participants were asked to sign informed consent before participation; an example of the consent form can be found as Extended data.23 Exclusion criteria were pregnant or lactating women, subjects with incomplete anthropometric measurements and/or biochemical data. The study was approved by The Hashemite University Ethics Committee, which authorized the protocols, tools, and procedures. All procedures were carried out according to the Declaration of Helsinki and the Institutional Board Review (IRB) (No.7/13/2018/2019; date approved 13/7/2018).\n\nDemographic data including age, sex, marital status, education level, lifestyle data (such as smoking status and physical activity), medical history, and family history of diseases were gathered through conducting a face-to-face structured interview in a private room using closed-ended questions, which can be found as Extended data.24 The interviewer asked the participants questions and then filled out the data form with the participant responses to ensure the accuracy of filled data (took place over 15-18 minutes). The participants were asked to provide verbal and written consent before participation.\n\nSocio-demographic data, including age, sex, marital status, education level, lifestyle data (such as smoking status and physical activity), medical history, and family history of diseases, were gathered through professional staff face-to-face interviews. These data were collected using a designed list of questions created for the study and put through a reliability test, after completion by 25 participants in a pilot study (α=0.77). The first 24 hours of dietary intake were recorded during these interviews. Moreover, participants were asked to schedule another meeting for fasting blood sample testing and collecting the second 24-hour dietary recall.\n\nEach participant had a fasting blood sample drawn after 8-12 hours of fasting, which was subsequently examined using a standardized procedure. A biochemical autoanalyzer (SEAL - AA3 HR - Colorimeter) was used to analyze the triglyceride (TG) and high-density lipoprotein (HDL). Using standardized techniques, well-trained examiners measured anthropometric indices. Participants were measured for body weight and height, wearing light clothing and bare feet, to the nearest 0.1 kg and 0.1 cm, respectively. With the individual standing, the waist circumference was measured using a flexible anthropometric tape on the horizontal plane halfway between the lowest rib and the iliac crest. At the place where the buttocks are at their widest comprehensive hip circumference was measured over thin clothing. The measurements of both circumferences were made to the nearest 0.1 cm. BMI was computed as weight divided by height square (kg)/(m2). The waist-to-height ratio was calculated (waist measurement divided by height measurement). Furthermore, in this study, five obesity indices were considered and calculated using standard formulas as follows: conicity index (CI) = WC (m)/(0.109 × √ (Bodyweight (kg)/Height (m))25; body adiposity index (BAI) = hip circumference (cm)/height (m)1.5–18)26; abdominal volume index (AVI) = (2 cm (waist)2 + 0.7 cm (waist-hip)2)/1,000)25; body roundness index (BRI0 = 365.2 − 365.5 × √(1 − ((WC/2π)2)/((0.5 × height))2))27; and weight-adjusted-waist index (WWI) = WC (cm) divided by the square root of weight (kg).28\n\nMoreover, cardiac function indices were considered and calculated, including an atherogenic index of plasma (AIP), lipid accumulation product (LAP), and cardiometabolic index (CMI), based on the following equations: LAP for males = (waist (cm)−65) × TG concentration (mmol/l), and for female = (waist (cm)−58) × TG concentration (mmol/l); CMI = TG/HDL-C ×(waist-to-height); AIP = Log (TG/HDL-C).29\n\nTwo nonconsecutive 24-hour day recalls measured dietary intake (weekday and weekend). The participants were instructed to recollect and list all foods and beverages they had from midnight to midnight the day before, along with their quantity, cooking technique, and the names of brands. To ascertain the typical dietary intake of B1, B2, B3, and B6 vitamins, the database of ingested items was connected to ESHA Food Processor Nutrition Analysis (RRID: SCR_022528) Software (version 11:0; ESHA Research). The average total intake of the selected vitamins after adjustment for energy intake was calculated, then using percentiles (33% and 66%); the subject intake was categorized as tertiles (T1 presents the lower intake, T3 presents medium intake, and T3 presents the higher intake). T1 was a value less than the 33 percentiles (B1: <1.6536; B2: <1.4200; B3: < 25.6736; B6: < 1.3700), T2 was the value between 33 and 66 percentiles (B1: 1.6536-2.2800; B2: 1.4200-1.9400; B3: 25.6736-36.6252; B6: 1.3700-1.9300), and T3 was the value above the 66 percentiles (B1: >2.2800; B2: >1.9400; B3: >36.6252; B6: >1.9300).\n\nTo prevent sample bias, we selected a representative sample size, which was calculated based on the total Jordanian population using online software Raosoft (Raosoft Inc., free online software, Seattle, WA, USA). Also, the incomplete anthropometric measurements and/or biochemical data were excluded to eliminate information bias. However, there were no self-reporting data to bypass recall bias, the interviewers were trained for data collection.\n\nThe sample size was calculated using the calculator Raosoft based on the Department of Statistics in 2020, adults represented 52.2% (5,621,970) of the total population (10,806,000) in Jordan. With a 5% error margin, 95% CI, and 50% response distribution, and after addition of 10%, the minimum sample size was 424 participants. The total number of final participants was 491.\n\nShapiro–Wilk test was used to verify the normality of variables. To describe the sample, descriptive statistical tests were used. Means and standard deviations (means± SD) were used to express continuous variables. Categorical variables, on the other hand, are displayed as frequencies and percentages (n (%)). Age groups stratified this analysis.\n\nMeans and standard deviation to present the continuous variables were calculated using an ANOVA test. Based on the sample distribution and test statistics, inferential statistics were applied, including the student’s t-test, chi-squared test, and independent samples t-test. The energy-adjusted intakes of B-vitamins were calculated by adding the expected mean nutrient intake of the study population to the residual derived from the regression analysis.30 This energy adjustment method was computed from the residuals of the regression model with total energy intake as the independent variable and the nutrient as the dependent variable. Pearson correlation coefficient was performed to determine the correlation between obesity indices and macronutrient intake. The percentage change in the index explained by nutrient intake was calculated using r-square from linear regression analysis considering age and sex as confounding factors. The statistical significance was set at p < 0.05. IBM SPSS Statistics (RRID: SCR_016479) version 25 (IBM, Chicago, IL, USA) was used.\n\n\nResults\n\nFrom the total sample, 198 participants were aged between 20-34 years old, 169 were aged 35-44 years old, and 124 were aged 45-65 years old. Participants aged between 20-34 years old had a mean weight of 74.04 ± 15.72 kg, WC 89.69 ± 13.15 cm, HC 102.98 ± 10.09 cm, and BMI 25.68 ± 4.96 kg/m2. The participants aged between 35-44 years old had a mean weight of 79.48 ± 15.32 kg, WC 97.18 ± 12.65 cm, HC 106.26 ± 9.62 cm, and BMI 28.00 ± 4.58 kg/m2. While participants aged between 45-65 years old had a mean weight of 84.40 ± 15.51 kg, WC 105.18 ± 15.59 cm, HC 108.22 ± 12.02 cm, and BMI 30.21 ± 5.94 kg/m2. Most of the participants in the different age groups were male (66.2, 68.0 and 79.0%, respectively) (Table 1).31 A total of 51.5% of participants aged 20-34 years old had a school-level education, while 57.4% and 50.8% of participants aged 35-44 and 45-65 years old, respectively, had a university-level education. Most of the participants aged 35-44 and 45-65 years old were single, whereas 43.9% of participants aged 20-34 years old were married and 55.6% were single. Participants aged 20-34 years old were either normal or overweight (49.5% and 30.3%, respectively). Participants aged 35-44 and 45-65 years old were either overweight (40.2% and 42.7%, respectively) or obese (32.0% and 41.1%, respectively). In addition, a larger proportion of the participants of all ages were physically active and smokers. Almost all the participants of different ages were disease-free (Table 1).\n\n* p-value < 0.05 considered statistically significant (2-tailed).\n\n** p-value is significant at the 0.01 level (2-tailed).\n\nThe average total intake of the macronutrients and selected B vitamins were 3,050.09 ± 914.90 Kcal for energy, 364.32 ± 118.76 g for carbohydrate, 98.28 ± 41.29 g for protein, 134.89 ± 58.84 g for fat, 2.09 ± 0.82 mg for unadjusted B1 vitamin, 1.79 ± 0.83 mg for unadjusted B2 vitamin, 32.84 ± 14.16 mg for unadjusted B3 vitamin, and 2.02 ± 6.29 mg for unadjusted B6 vitamin. The mean intake and tertiles range for adjusted B vitamins were: 2.09 ± 0.59 mg (T1: <1.89; T2: 1.89-2.38; T3: >2.38) for energy-adjusted B1 vitamin, 1.79 ± 0.70 mg (T1: <1.54; T2: 1.54-1.88; T3: >1.88) for energy-adjusted B2 vitamin, 32.8 ± 12.34 mg (T1: <26.11; T2: 26.11-36.33; T3: >36.33) for energy-adjusted B3 vitamin, and 2.02 ± 6.22 mg (T1: <1.47; T2: 1.47-2.06; T3: >2.06) for energy-adjusted B6 vitamin.\n\nThe mean score of indices of obesity and cardiac function among the adjusted B vitamins tertiles are shown in Table 2. Among adjusted vitamin B1 intake tertiles, the CI and AVI index score significantly decreased as the intake of B1 intake increased (CI: T1 = 1.31 ± 0.01 vs. T3 = 1.28 ± 0.01, p = 0.031; AVI: T1=20.75 ± 0.64 vs. T3 = 18.14 ± 0.43, p = 0.02). Among adjusted B6 tertiles the score of the CI (T1 = 1.33 ± 0.01 vs. T3 = 1.27 ± 0.01, p < 0.001), AVI (T1 = 20.62 ± 0.57 vs. T3 = 17.43 ± 0.36, p < 0.001), BRI (T1 = 2.19 ± 0.09 vs. T3 = 1.60 ± 0.06, p < 0.001), WWI (T1 = 11.16 ± 0.09 vs. T3 = 10.71 ± 0.06, p < 0.001), LAP (T1 = 69.29 ± 4.48 vs. T3 = 50.31 ± 3.09, p = 0.048), AIP (T1 = 0.55 ± 0.03 vs. T3 = 0.46 ± 0.02, p = 0.034) decreased significantly as we moved from T1 to T3.\n\n* p-value < 0.05 considered statistically significant (2-tailed).\n\n** p-value is significant at the 0.01 level (2-tailed).\n\nThe association between indices of obesity and cardiac function with the adjusted energy intake of B vitamins among the total sample and based on sex are illustrated in Table 3. The energy-adjusted intake of B1 for the total sample had a significantly inverse weak correlation with AVI (r = -0.156, p = 0.001) and BRI (r = -0.111, p = 0.014). Among male participants, similar correlations were detected between energy adjusted B1 intake and BAI (r = -0.207, p < 0.001), AVI (r = -0.145, p = 0.007), and BRI (r = -0.163, p = 0.002). While, among female participants, there was a significant weak inverse correlation between BAI and energy adjusted B2 (r = -0.180, p = 0.029) and B6 intake (r = -0.212, p = 0.010). Moreover, there was a significant weak inverse association between energy adjusted B6 intake and AVI (r = -0.252, p = 0.002), BRI (r = -0.230, p = 0.005), and LAP (r = -0.179, p = 0.030) indices.\n\n** Correlation is significant at the 0.01 level (2-tailed).\n\n* Correlation is significant at the 0.05 level (2-tailed).\n\nFor more details, the percentage changes in indices of obesity and cardiac function explained by energy-adjusted B vitamins intakes using the linear regression model are presented in Table 4. Among B vitamins, only vitamin B1 significantly explained 2.43% of changes observed in the AVI score and 1.24% of changes observed in the BRI score (p < 0.05).\n\n* p-value < 0.05 considered statistically significant (2-tailed).\n\n\nDiscussion\n\nObesity is considered to be one of the malnutrition forms, which develops individually and as a result of unbalanced nutrition.2 Based on The World Health Organization (WHO), obesity is defined as the “double burden of malnutrition” and indicates that it may occur more frequently in socioeconomically underdeveloped and poorly nourished societies side by side with malnutrition, and in consequence, chronic diseases may develop.32 Vitamins B1 (thiamine), B2 (Riboflavin), B3 (niacin), and B6 (pyridoxine), all of which are vital for the metabolism of energy, carbohydrate, lipid, and amino acid, as well as the regulation of the cellular redox state.10 Some studies have revealed that obesity is associated with low levels of fruit intake, total diet quality, and micronutrient intake compared to normal BMI, which means that people living with obesity may consume fewer micronutrients due to the foods they eat and subsequently may lead to low levels of water-soluble vitamins.10,33\n\nThe current study studied the association between dietary intake of B vitamins; specifically, B1, B2, B3, and B6, with indices of obesity and cardiac function were studied. Among these B vitamins, B1 and B6 had a significant association with some of the obesity indices; B2 with BAI indices, and B6 had a significant association with LAP (one of the cardiac function indices) The result revealed that the score of obesity indices CI and AVI decreased with an increase in the dietary intake of vitamin B1. Moreover, the energy-adjusted intake of B1 had a significantly inverse weak correlation with AVI and BRI among the total sample and male participants. Energy-adjusted B1 vitamin significantly explained 2.43% of changes observed in the AVI and 1.24% of changes observed in the BRI indices (p < 0.05). In addition, based on this study result, increasing the intake of B6 led to reductions in the score of obesity (CI, AVI, BRI, WWI) and cardiac function indices (LAP and AIP).\n\nBy these results, Kerns et al., reported that 15.5–29% of patients with obesity who seek bariatric surgery have malnutrition disease, specifically, B1 deficiency.34 In line with the present findings, B1 deficiency was found in children with obesity, and most of those cases were subclinical.35 Kardas et al., observed significantly decreased levels of vitamin B2, vitamin B12, and B9 in the obesity and metabolic syndrome groups.2 By contrast, they observed an increased level of B1 with a positive correlation with LDL-C and a negative correlation with HOMA-IR and body weight in the target group.2 Studies show that vitamin B2 deficiency causes functional alterations in adipocytes, and thus has pro-inflammatory and proinsulin effects, resulting from increased adipocytes.36 Moreover, in the subjects with obesity, an inverse correlation was found between vitamin B6 and body weight.2 Gunanti et al. (2014) examined the associations between serum B vitamins and vitamin intake with body fat in Mexican American children aged 8–15 years. B1 and B2 intakes were inversely associated with BMI and trunk fat mass (b:21.26, p < 0.05; b: 21.37, p < 0.05).6 Different suggested mechanisms have been introduced to describe the correlation between B-vitamin deficiency and obesity occurrence, all are summarized in Figure 1. The interaction mechanism between the reduced serum B-complex level and obesity includes the reduction in B1, B2, B3, and B6 levels associated with an increased risk of metabolic syndrome, which is considered one of the major cases of obesity.5 Also, decreases in the levels of B1 and B2 are correlated with increased BMI,6 and B6 regulates the expression of peroxisome proliferator-activated receptor gamma (PPARγ), which is a target gene that plays a key role in adipocyte gene expression and adipogenesis.12 Additionally, decreased B1, B3, and B6 concentrations correlate significantly with an increased risk of insulin resistance, metabolic dysfunction, and obesity.37 Moreover, generally, B vitamins have a fundamental role in the lipid and lipoprotein metabolism cascade. Therefore, quantitative or qualitative defects in B vitamins will negatively impact the metabolism of lipid derivatives.38 Also, B2 plays a vital role in energy-expenditure adipocyte gene regulation at the epigenetic level.39 The final suggested mechanism is that increased body weight leads to the reduction of vitamin B6 levels by inducing systemic oxidative stress, which leads to stimulating adipocytokines dysregulation.6,22\n\n(1) Deficiencies in B7, B6, B9, and B12 lead to energy metabolism disruption, which induces the production of reactive oxygen species, inflammation, and lipogenesis.6 (2) Reduced levels of B1, B2, B3, and B6 levels are associated with an increased risk of metabolic syndrome, which is considered one of the major cases of obesity.5 (3) Decreased levels of B1 and B2 are correlated with increased body mass index (BMI).6 (4) B6 regulates the expression of peroxisome proliferator-activated receptor gamma)PPARg(target genes, which play a key role in adipocyte gene expression and adipogenesis.41 (5) Decreased B1, B3, and B6 concentrations are significantly correlated with increased risk of insulin resistance, metabolic dysfunction and obesity.42 (6) B vitamins are fundamental in the lipid and lipoprotein metabolism cascade. Therefore, quantitative or qualitative defects in B vitamins will negatively impact the metabolism of lipid derivatives.37 (7) B2 plays a vital role in energy-expenditure adipocyte gene regulation at the epigenetic level.43 (8) Increased body weight leads to the reduction of vitamin B6 levels by inducing systemic oxidative stress, which leads to stimulating cytokines dysregulation.6,38\n\nStudies investigating the prevalence of B1 deficiency among patients with cardiovascular diseases (CVDs) concluded that B1 deficiency could have a role in the development of CVDs.15 Odum et al. (2012) found that the mean plasma vitamins B1, B3, B6 and C concentrations of subjects with metabolic syndrome were significantly lower than that of controls (p = 0.001, 0.05, 0.045, 0.001, respectively). Also, 14% and 32% of subjects had inadequate vitamin B1 and vitamin C status, respectively.10 Additionally, Wu et al., found a linear inverse relationship between dietary vitamin B1, niacin, B6, and metabolic syndrome, and a non-linear inverse relationship was found between dietary vitamin B2 and metabolic syndrome.5 It was noted that vitamin B6 supplementation is vital in preventing metabolic syndrome and pyridoxine levels were lower in patients with metabolic syndrome compared to those in healthy patients.39 They suggested that a higher intake of vitamin B1, B2, niacin, B6, and dietary folate equivalent was associated with a reduced risk of metabolic syndrome.5 Not like other results, Kardas et al., found that B1 levels were high in subjects with obesity and metabolic syndrome; they explained this difference by the fact that these individuals typically consumed large quantities of bread and cereals, which are considered major sources of B1.2 Many suggested mechanisms have been introduced to describe the association between B-vitamin deficiency and metabolic syndrome and coronary heart diseases, all are summarized in Figure 2.\n\n(1) B3 intake leads to decreased serum levels of low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), and triglycerides (TG). Also, increased levels of high-density lipoprotein cholesterol (HDL).19 (2) Vitamins B2, B6, B9, and B12 are vital in homocysteine demethylation into methionine, leading to decreased risk of atherosclerosis.13,19 (3) Decreased levels of folate intake lead to decreased DNA-methylation, which has been detected in atherosclerotic lesions.44 Also, B6 is associated with reduced risk of metabolic syndrome.5 (4) Low B1, B3, and B6 levels were associated with increased insulin resistance, metabolic dysfunction, and increased risk of atherosclerosis, obesity, metabolic syndrome, diabetes, and cardiovascular disease.10,40\n\nB3 intake is suggested to decrease serum levels of LDL, VLDL, and TG, as well as, increase levels of HDL.19,22 Also, vitamins B2 and B6 have a vital role in homocysteine demethylation into methionine, which leads to decreased risk of atherosclerosis.13,19 Additionally, B6 is associated with a reduced risk of metabolic syndrome.5 Lastly, low levels of B1, B3, and B6 are associated with increased insulin resistance, metabolic dysfunction, and increased risk of atherosclerosis, obesity, metabolic syndrome, diabetes, and cardiovascular disease.10,40\n\nThis study is one of the early studies that placed importance on examining the relationship between inadequate dietary intake of energy-releasing B-vitamins, and each of the indices of obesity and cardiac function in healthy individuals. There are not enough studies that clarify the correlation between B vitamins and indices of obesity and cardiac function. This provides the scope to highlight the significance of dietary consumption and the part that nutritional inadequacies play in the prevalence of obesity and heart disease.\n\nThe present study had certain limitations. First, because the study was cross-sectional, it was impossible to conclusively establish a causal link between obesity, cardiac function indices, and dietary intake of B vitamins. The availability of both conventional and innovative anthropometric measures as well as cardiac function indices is one of our study’s key strengths. Additionally, because the current data were gathered before the COVID-19 pandemic, they can be used to compare studies done before and after the pandemic by researchers in the same field. Another key benefit of the study is the originality of its investigation of the relationship between indicators of cardiac function and several chosen nutrients. We selected a representative sample size to prevent sample bias, which was calculated based on the total Jordanian population using online software. Also, the incomplete anthropometric measurements and/or biochemical data have been excluded to eliminate information bias. However, there were no self-reporting data to bypass recall bias, the interviewers were trained for data collection.\n\n\nConclusions\n\nIn conclusion, after energy adjustment, obesity indices are inversely associated with B1, B2, and B6 vitamins. Specifically, AVI and BRI were inversely associated with B1 and B6 vitamins, whereas BAI was inversely associated with B2 vitamins among female participants. Only the B6 vitamin was inversely associated with LAP and AIP among cardiac function indices. Increasing the intake of these vitamins (B1, B2, and B6) results in reducing the score of obesity (CI, AVI, BRI, WWI) and cardiac function indices (LAP and AIP), which in consequence may help reduce the occurrence of obesity and related coronary diseases.",
"appendix": "Data availability\n\nZenodo: The impact of energy releasing B-vitamin intake on indices of obesity and cardiac function: a cross-sectional study, https://doi.org/10.5281/zenodo.8159116. 31\n\nThe project contains the following underlying data:\n\n• Supplementary File 1-Energy releasing B vitamins 13-1-2023.sav (Anonymized participant data used in this study)\n\nZenodo: The impact of energy releasing B-vitamin intake on indices of obesity and cardiac function: a cross-sectional study, https://doi.org/10.5281/zenodo.8167422. 24\n\nThis project contains the list of interview questions used with 24-hour recall form.\n\nZenodo: The impact of energy releasing B-vitamin intake on indices of obesity and cardiac function: a cross-sectional study, https://doi.org/10.5281/zenodo.8167441. 23\n\nThis project contains an example of the consent form used.\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 participants for their patience and great help. Grammarly software program has been used to enhance language editing.\n\n\nReferences\n\nMonteverde D, Gómez-Consarnau L, Suffridge C, et al.: Life’s utilization of B vitamins on early Earth. Geobiology. 2017; 15(1): 3–18. PubMed Abstract | Publisher Full Text\n\nKardaş F, Yücel A, Kendirci M, et al.: Evaluation of micronutrient levels in children and adolescents with obesity and their correlation with the components of metabolic syndrome. Turk. J. Pediatr. 2021; 63(1): 48–68. Publisher Full Text\n\nMotamed S, Ebrahimi M, Safarian M, et al.: Micronutrient intake and the presence of the metabolic syndrome. N. Am. J. Med. Sci. 2013; 5(6): 377–385. PubMed Abstract | Publisher Full Text\n\nVia M: The malnutrition of obesity: micronutrient deficiencies that promote diabetes. ISRN Endocrinol. 2012; 2012: 1–8. Publisher Full Text\n\nWu Y, Li S, Wang W, et al.: Associations of dietary vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12 and folate equivalent intakes with metabolic syndrome. Int. J. Food Sci. Nutr. 2020; 71(6): 738–749. PubMed Abstract | Publisher Full Text\n\nGunanti I, Marks G, Al-Mamun A, et al.: Low serum vitamin B-12 and folate concentrations and low thiamin and riboflavin intakes are inversely associated with greater adiposity in Mexican American children. J. Nutr. 2014; 144(12): 2027–2033. PubMed Abstract | Publisher Full Text\n\nYanni AE, Kokkinos A, Psychogiou G, et al.: Daily consumption of fruit-flavored yoghurt enriched with vitamins B contributes to lower energy intake and body weight reduction, in type 2 diabetic patients: a randomized clinical trial. Food Funct. 2019; 10(11): 7435–7443. PubMed Abstract | Publisher Full Text\n\nBarazzoni R, Silva V, Singer P: Clinical biomarkers in metabolic syndrome. Nutr. Clin. Pract. 2014; 29(2): 215–221. Publisher Full Text\n\nMcCracken E, Monaghan M, Sreenivasan S: Pathophysiology of the metabolic syndrome. Clin. Dermatol. 2018; 36(1): 14–20. Publisher Full Text\n\nOdum E, Wakwe V: Plasma concentrations of water-soluble vitamins in metabolic syndrome subjects. Niger. J. Clin. Pract. 2012; 15: 442–447. PubMed Abstract | Publisher Full Text\n\nUllegaddi R, Powers H, Gariballa S: B-group vitamin supplementation mitigates oxidative damage after acute ischaemic stroke. Clin. Sci. 2004; 107: 477–484. PubMed Abstract | Publisher Full Text\n\nFolsom A, Desvarieux M, Nieto F, et al.: B vitamin status and inflammatory markers. Atherosclorosis. 2003; 169: 169–174. Publisher Full Text\n\nHuang T, Zheng Y, Qi Q, et al.: DNA Methylation Variants at HIF3A Locus, B-Vitamin Intake, and Long-term Weight Change: Gene-Diet Interactions in Two U.S. Cohorts. Diabetes. 2015; 64(9): 3146–3154. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDick K, Nelson C, Tsaprouni L, et al.: DNA methylation and body-mass index: a genome-wide analysis. Lancet. 2014; 383: 1990–1998. Publisher Full Text\n\nEshak E, Arafa A: Thiamine deficiency and cardiovascular disorders. Nutr. Metab. Cardiovasc. Dis. 2018; 28(10): 965–972. Publisher Full Text\n\nHuang T, Li K, Ksimi S, et al.: Effect of vitamin B-12 and n-3 polyunsaturated fatty acids on plasma homocysteine, ferritin, C-reaction protein, and other cardiovascular risk factors: A randomized controlled trial. Asia Pac. J. Clin. Nutr. 2015; 24: 403–411. PubMed Abstract | Publisher Full Text\n\nBlacher J, Czernichow S, Paillard F, et al.: Cardiovascular effects of B-vitamins and/or N-3 fatty acids: the SU. FOL. OM3 trial. Int. J. Cardiol. 2013; 167(2): 508–513. Publisher Full Text\n\nValko M, Rhodes C, Moncol J, et al.: Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 2006; 160(1): 1–40. Publisher Full Text\n\nFiorito G, Guarrera S, Valle C, et al.: B-vitamins intake, DNA-methylation of one carbon metabolism and homocysteine pathway genes and myocardial infarction risk: the EPICOR study. Nutr. Metab. Cardiovasc. Dis. 2014; 24(5): 483–488. PubMed Abstract | Publisher Full Text\n\nZhu J, Xun P, Kolencik M, et al.: Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials. Nutrients. 2022; 14(8): 1608. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWan P, Moat S, Anstey A: Pellagra: a review with mphasis on hotosensitivity. Br. J. Dermatol. 2011; 164(6): 1188–1200. PubMed Abstract | Publisher Full Text\n\nVillines TC, Kim AS, Gore RS, et al.: Niacin: The evidence, clinical use, and future directions. Curr. Atheroscler. Rep. 2011; 14: 49–59.\n\nAgraib LM, Al-Shami I, Alkhatib B, et al.: The impact of energy releasing B-vitamins intake on obesity indices and coronary heart indices: a cross-sectional study (v1, consent form). [Dataset]. Zenodo. 2023. Publisher Full Text\n\nAgraib LM, Al-Shami I, Alkhatib B, et al.: The impact of energy releasing B-vitamins intake on obesity indices and coronary heart indices: a cross-sectional study (v1, Study Questionnaire). [Dataset]. Zenodo. 2023. Publisher Full Text\n\nGowda V, Philip K: Abdominal volume index and conicity index in predicting metabolic abnormalities in young women of different socioeconomic classes. Int. J. Med. Sci. Public Health. 2016; 5(7): 1452–1456. Publisher Full Text\n\nWang H, Chen Y, Sun G, et al.: Validity of cardiometabolic index, lipid accumulation product, and body adiposity index in predicting the risk of hypertension in Chinese population. Postgrad. Med. 2018; 130(3): 325–333. PubMed Abstract | Publisher Full Text\n\nChang Y, Guo X, Chen Y, et al.: A body shape index and body roundness index: Two new body indices to identify diabetes mellitus among rural populations in northeast China. BMC Public Health. 2015; 15: 794. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCai S, Zhou L, Zhang Y, et al.: Association of the Weight-Adjusted-Waist Index With Risk of All-Cause Mortality: A 10-Year Follow-Up Study. Front. Nutr. 2022; 9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWakabayashi I: Associations of Smoking and Drinking with New Lipid-Related Indices in Women with Hyperglycemia. Women’s Health Reports. 2021; 2(1): 23–31. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWillett W, Stampfer MJ: Total energy intake: implications for epidemiologic analyses. Am. J. Epidemiol. 1986; 124(1): 17–27. Publisher Full Text\n\nAgraib LM, Al-Shami I, Alkhatib B, et al.: The impact of energy releasing B-vitamin intake on indices of obesity and cardiac function: a cross-sectional study. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nWHO: besity and overweight 2020.Reference Source\n\nAgarwal S, Reider C, Brooks JR, et al.: Comparison of prevalence of inadequate nutrient intake based on body weight status of adults in the United States: an analysis of NHANES 2001–2008. J. Am. Coll. Nutr. 2015; 34(2): 126–134. PubMed Abstract | Publisher Full Text\n\nKerns JC, Arundel C, Chawla LS: Thiamin deficiency in people with obesity. Adv. Nutr. 2015; 6(2): 147–153. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDensupsoontorn N, Srisawat C, Chotipanang K, et al.: Prevalence of and factors associated with thiamin deficiency in obese Thai children. Asia Pac. J. Clin. Nutr. 2019; 28(1): 116–121. PubMed Abstract | Publisher Full Text\n\nMazur-Bialy AI, Pocheć E: Vitamin B2 deficiency enhances the pro-inflammatory activity of adipocyte, consequences for insulin resistance and metabolic syndrome development. Life Sci. 2017; 178: 9–16. PubMed Abstract | Publisher Full Text\n\nIbrahim GR, Shah I, Gariballa S, et al.: Significantly elevated levels of plasma nicotinamide, pyridoxal, and pyridoxamine phosphate levels in obese Emirati population: A cross-sectional study. Molecules. 2020; 25(17): 3932. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFurukawa S, Fujita T, Shimabukuro M, et al.: Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 2017; 114(12): 1752–1761. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu Z, Li P, Zhao Z-H, et al.: Vitamin b6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation in apoe−/− mice fed with high-fat diet. J. Diabetes Res. 2016; 2016: 1–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShen J, Lai C-Q, Mattei J, et al.: Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study. Am. J. Clin. Nutr. 2010; 91(2): 337–342. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYanaka N, Kanda M, Toya K, et al.: Vitamin B6 regulates mRNA expression of peroxisome proliferator-activated receptor-γ target genes. Exp. Ther. Med. 2011; 2(3): 419–424. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPatrini C, Griziotti A, Ricciardi L: Obese individuals as thiamin storers. Int. J. Obes. 2004; 28(7): 920–924. PubMed Abstract | Publisher Full Text\n\nHino S, Sakamoto A, Nagaoka K, et al.: FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure. Nat. Commun. 2012; 3(1): 1–12.\n\nJiang Y, Zhang H, Sun T, et al.: The comprehensive effects of hyperlipidemia and hyperhomocysteinemia on pathogenesis of atherosclerosis and DNA hypomethylation in ApoE−/− mice. Acta Biochim. Biophys. Sin. 2012; 44(10): 866–875. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "239615",
"date": "12 Feb 2024",
"name": "Małgorzata Szczuko",
"expertise": [
"Reviewer Expertise nutrition",
"metabolic syndrom",
"vitamin B"
],
"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 article is clearly written and easy to read. Although it seems that at the same time it does not exhaust the topic in some respects\n2. A major advantage of the study is the number of patients examined and the well-described statistics of the results\n3. the summary lacks a specific summary and conclusion\n4. in the introduction, please also include women with PCOS, in the course of which insulin resistance, metabolic syndrome and obesity develop ref [1] 5. the age of the examined patients is missing in table 1\n6. the following issues should be discussed in the discussion: - increased demand for B vitamins in people with obesity and diabetes re [2]. - peripheral neuropathy ref [3] - effects of supplementation and over supplementation of B vitamins ref [4]\n7. It is recommended to use the provided literature to improve and improve 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?\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": "11052",
"date": "13 Apr 2024",
"name": "Buthaina Alkhatib",
"role": "Author Response",
"response": "The article is clearly written and easy to read. Although it seems that at the same time it does not exhaust the topic in some respects Response: Thank you 2. A major advantage of the study is the number of patients examined and the well-described statistics of the results Response: thank you 3. the summary lacks a specific summary and conclusion Response: it has been revised (conclusion: Increasing the consumption of B1, B2, and B6 may significantly lower values of indices of obesity and cardiac function regardless of sex differences. Thus reducing the occurrence of obesity and related coronary heart diseases 4. in the introduction, please also include women with PCOS, in the course of which insulin resistance, metabolic syndrome and obesity develop ref [1] Response: it has been added 5. the age of the examined patients is missing in table 1 Response: the table was prepared regarding the age group, as shown in raw 1) 6. the following issues should be discussed in the discussion: - increased demand for B vitamins in people with obesity and diabetes re [2]. - peripheral neuropathy ref [3] - effects of supplementation and over-supplementation of B vitamins ref [4] Response: it has been provided (references 35, 36). But reference no 4 is not within the scope of discussion. 7. It is recommended to use the provided literature to improve and improve the article. Response: many thanks for your suggestions, it has been provided 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? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes"
}
]
}
] | 1
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https://f1000research.com/articles/12-1382
|
https://f1000research.com/articles/13-893/v1
|
06 Aug 24
|
{
"type": "Data Note",
"title": "Dataset of a national survey on online gambling activities among young people in Portugal.",
"authors": [
"Ana Rita Farias",
"Ana Cristina Antunes",
"Ana Cristina Antunes"
],
"abstract": "Abstract*\nBackground Recent advancements in online gambling have significantly increased the popularity and participation in gambling activities among the general population, specifically the young generations. These changes are reshaping gambling behaviors, attracting a growing number of enthusiasts. This paper describes a dataset that maps online gambling activities among young individuals in Portugal, providing insights into their gambling prevalence, habits, behaviors, preferences, and potential antecedents and consequences of these activities.\n\nMethods A survey was conducted with a representative sample of 1,993 young people in Portugal, aged between 18 and 34, to gather data on their activities. This methodology involved a quantitative telephone survey conducted in March and April 2023, utilizing quota sampling to ensure representation across various regions. The data collection process employed Computer Assisted Telephone Interviewing (CATI) and involved rigorous quality control measures to ensure accuracy and reliability.\n\nConclusion The dataset generated from this survey provides valuable insights into the patterns of online gambling activities among young Portuguese individuals. It allows researchers to explore potential risk factors, including gambling-related harm, and to understand the sociodemographic factors influencing gambling behaviors. The findings can inform interventions and policies aimed at mitigating the negative consequences of online gambling among youth.",
"keywords": [
"Online Gambling Behavior",
"Young Gamblers",
"Antecedents",
"Consequences",
"and Sociodemographic Factors"
],
"content": "Introduction\n\nThe digital world has optimized numerous daily tasks, such as grocery shopping and communication. However, it has also introduced new problems or new forms of old problems. One industry significantly affected by digital transformation is gambling, and the online gambling market is growing worldwide, driven by technological advancements and increasing consumer confidence in online monetary transactions. According to Statista (2024), the revenue of the online gambling market is projected to reach US$100.90bn in 2024, with an annual growth rate (2024-2029) of 6.20%, resulting in a projected market volume of US$136.30bn by 2029, while the number of users is expected to reach 281.3 million by 2029. Notably, online gambling is currently the fastest-growing form of gambling.\n\nThe easy access and convenience of online gambling, which can be done anywhere, at any time, and for an unlimited duration, coupled with the increasing availability of digital platforms, the low costs and incentives of online gambling, and the possible anonymity, has led to a rise in the number of people engaging in these forms of gambling for money.1 These trends have raised concerns among various professionals, including educators and healthcare providers, who are increasingly worried about the potential negative effects of online gambling, such as financial problems and impacts on mental health.2,3 Indeed, when compared with land-based gambling, online gambling has a greater addictive potential due to a series of situational and structural aspects, such as availability, accessibility, immediacy of reinforcement, or speed and frequency of gambling.4,5 Additionally, it is associated with a range of negative outcomes that make it potentially harmful to individuals’ financial, physical, and emotional well-being, as well as to their families and society as a whole.2,3 Moreover, despite clear age restrictions, literature suggests that the prevalence of online gambling activities is significantly higher among younger age groups compared to adults.6 Understanding this issue among young people is crucial, as these new forms of online gambling seem particularly enticing to this population.\n\nTo address the urgent need for understanding and mapping online gambling activities among Portuguese youth, this research aims to shed light on this phenomenon within this less-studied generational cohort. A telephone survey was conducted in March and April 2023, targeting a random sample of 1,993 young individuals aged 18 to 34, residing in Portugal.\n\n\nMethods\n\nThis project, which intends to map online gambling activities and examine potential antecedents and outcomes among young individuals in Portugal, received data collection support from GfK.\n\nThis quantitative study included both male and female participants, aged 18 to 34, living in Portugal. The sample consisted of 1,993 participants, divided into two sub-samples proportionately distributed across key regions in Portugal (Table 1). Sub-sample 1 investigated the possible antecedents, while Sub-sample 2 examined the possible consequences. Respondents were selected using the quota sampling method, incorporating variables such as gender, age (categorized into 2 groups), and region (using the Portuguese NUTS II regions). Quota sampling intends “to approximate the results that would be obtained with probabilistic samples” (Romero & Bologna, 2013, p. 288),7 thus reproducing the characteristics of the study population. Households were chosen by randomly generating fixed and mobile telephone numbers, ensuring representation across the different Portuguese regions based on the initial matrix. The random generation of numbers followed assigned prefixes specific to each region and operator.\n\nFollowing a pilot phase designed to enhance the accuracy, clarity, and comprehensiveness of the instrument, establish the optimal duration for high-quality interviews, evaluate respondents’ comprehension of the questions, and validate the consistency of responses using the Computer Assisted Telephone Interviewing (CATI) script, a final questionnaire was developed.\n\nData was collected through telephone interviews utilizing the CATI system, supported by a questionnaire developed by the research team. The fieldwork took place between January 28th and March 25th, 2023, with a team of 47 interviewers trained by GfK Metris. Interviews were conducted on weekdays from 5 PM to 10 PM and on weekends from 11 AM to 10 PM, covering a range of suitable time slots for data collection.\n\nComprehensive quality control measures were implemented to ensure the accuracy and reliability of the data. Interviewers underwent thorough training, and we limited the inclusion of new interviewers to 25% of the total interviews. Additionally, interviews were distributed among different interviewers in each region to avoid concentration and potential bias.\n\nThe CATI system enabled the automatic validation of the data file at multiple levels, including a response code validation for each question and ensuring a logical flow between questions, such as skips and filters, to maintain the questionnaire’s structure integrity. A field technician from Metris GfK supervised the interviewers, closely monitoring adherence to household and respondent selection criteria, overseeing interview conditions and duration, and providing on-site support when needed. Errors or missing information in the survey were reviewed by the IT Department, which determined appropriate procedures to rectify issues, such as contacting respondents for missing data or voiding interviews with abnormal non-response rates.\n\nAdditionally, a separate supervision process involved recontacting at least 10% of each interviewer’s respondents to ensure data accuracy and consistency. Open-ended questions were transcribed using CATI software (e.g. https://www.b2binternational.com/research/methods/faq/what-is-cati/), capturing 100% of the responses. This facilitated the implementation of coding plans specific to each question, ensuring proper analysis and interpretation of qualitative data.\n\nAfter the coding process and comprehensive validation of the computer file, the data were ready for tabulation and further analysis using dedicated software. These measures ensured the overall quality and reliability of the collected data, enabling insightful findings on online gambling behaviors and meaningful conclusions on their predictors and consequences.\n\nThe questionnaire is structured in four sections: after an initial screening, there is a section intended to map gambling activities in general, followed by a focus on online gambling activities, habits, preferences and problem gambling, while the third section is designed to gather information on gambling antecedents and consequences and the final section obtains demographic information of the respondents.\n\nA) Initial screening:\n\nThe initial screening measure aims to gain a preliminary understanding of participants’ gambling involvement and establish a baseline for further assessment. The key measure is Gambling Participation which determines whether the participant has ever engaged in any form of gambling (either online or offline). This essential question is posed with two response options: “1 - Yes” for those who gambled at least once during their lifetime and “2 - No” for those who have not. By identifying participants with prior gambling experience, researchers can segment the sample, which serves as a crucial step in understanding the dynamics of participation and involvement with gambling activities.\n\nB) Main measures across the two samples\n\n1) Gambling activities map\n\nThe following set of measures is designed to provide a comprehensive assessment of participants’ gambling experiences, habits, and spending patterns.\n\n• Gambling Experience Offline/Online Measure: Investigates whether participants have ever bet money on offline or online games using a dichotomous question (1 - Yes; 2 - No).\n\n• Gambling Frequency Offline/Online Measure: A single close-ended question tracks the frequency of participants’ gambling activities over their lifetime. It records the number of gambling occasions both online and offline, utilizing a frequency scale ranging from 1 (never) to 7 (41 or more occasions).\n\n• Gambling Participation Past 12 Months and Past 3 Months Offline/Online Measures: Adapted from Canale et al. (2016),8 two close-ended questions gather information on the number of times participants engaged in online or offline gambling activities during the previous 12 months and the previous 3 months, respectively. Responses are recorded on a 5-point frequency scale, ranging from 1 (never) to 7 (41 or more occasions).\n\n• Gambling Frequency per Game Types in the Last 12 Months and Last 3 Months Measure: Based on Canale et al. (2016),8 this measure assesses the frequency of participation in 11 different gambling activities, such as slot machines, Euromillions, bingo, instant lottery, sports betting, and poker. The gambling frequency on these different game types is measured using a 7-point frequency scale ranging from 1 (never) to 7 (41 or more occasions).\n\n• Gambling Average Monthly Expenditure Measure: Derived from Hubert (2015),9 this close-ended question measures participants’ gambling expenditures in a typical month during the year preceding data collection. Participants are asked to indicate their monthly spending amount using a 6-point scale ranging from 1 (20€ or less) to 6 (100€ or more).\n\n• Gambling Spending Typical Month Measure: This open-ended question requires participants to specify the exact amount they spend in a typical month on both online and offline gambling activities.\n\n2) Online Gambling Activities Map\n\nThis set of measures is designed to explore various aspects of online gambling behavior and problematic gambling tendencies:\n\n• Start Browsing Age: assesses, by an open question, the age at which participants began browsing independently the internet.\n\n• Device Usage Frequency Measure: This measure assesses the frequency of device usage for online gambling, including personal computers, smartphones, and gaming consoles. Participants are asked to report how often they use for each device on a 5-point scale ranging from 1 (never) to 5 (always).\n\n• Gambling location frequency: This measure explores the frequency of online gambling in various locations, such as home, work, university/school, and outdoors. Participants are asked to indicate how often they gamble in each location using a 5-point scale ranging from 1 (never) to 5 (always).\n\n• Online Betting Time Preference: Assesses, through a single question, the preferred time of day for online betting. Participants are asked to select their preferred time from four options: morning, afternoon, night, and dawn.\n\n• Online Gambling Attraction Levels: An 11-item scale adapted from Hubert (2015)9 assesses participants’ attraction to various aspects of online gambling, such as anonymity, convenience, diversity of games, and connection with others. Each item is rated on a 5-point scale, ranging from 1 (not at all attractive) to 5 (very attractive).\n\nGambling-related Problem: Gambling problems were assessed using a version of the DSM-IV pathological gambling criteria (American Psychiatric Association, 2000), adapted from Canale et al. (2016).8 Seven gambling-related problems (e.g., problems with spouse/partner and/or other people, financial problems, work-related problems) experienced in the previous 12 months are assessed. To go beyond the mere presence or absence of a symptom/problem, participants are asked to indicate the frequency that they experienced each symptom, using a 5-point frequency scale from 1 (Never) to 4 (Always).\n\nC) Specific measures s1 (Antecedents) and s2 (consequents)\n\n1) Mapping antecedents (s1):\n\nThis set of measures is designed to assess participants’ gambling antecedents comprehensively:\n\n• Gambling Motives measure: A 25-item measure adapted from Hubert (2019)10 is used to assess peoples’ motives for gambling. Participants responded by indicating on a 7-point scale (1 being ‘does not apply to me at all’ and 7 ‘applies totally to me’), how much each motive could be applied to them.\n\n• Gambling Advertising measure: A 10-item scale adapted from Noble et al. (2022)11 measures the perceived exposure to several types of gambling advertising and promotions. Participants are asked to indicate whether they had been aware of ads or promotions for gambling in several media (e.g., ‘Ads on TV’, ‘Ads on social media’, ‘Pop-ups on websites’, ‘Celebrities promoting gambling’) in the previous 30 days, using a 5-point frequency scale ranging from 1 (never) to 5 (always).\n\n2) Mapping consequents (s2):\n\nThis set of measures is designed to comprehensively assess the participants’ main gambling consequences:\n\n• Consequences for health and well-being: The Short Form Health Survey (SF-12) by Ware et al. (1996)12 is used to assess overall health and well-being across eight domains, including physical functioning, role limitations due to physical and emotional problems, bodily pain, general health perceptions, vitality, social functioning, and mental health. It is widely used in clinical and research settings to provide a quick, reliable assessment of physical and mental health status.\n\n• Consequences Due to Gambling Measure: All 24 items of this scale adapted from Hubert (2015)9 concern several consequences that can be derived from gambling (e.g., financial, for social and/or family life, on the professional sphere or for psychological and/or physical health). Participants are asked to rate the extent and severity of these various gambling-related consequences on a 6-point scale from 0 (not at all serious) to 5 (extremely serious). Items include “I couldn’t concentrate at work,” “At home, I was only physically present,” “It took up too much of my time,” and “I lost job or professional, social, or marital opportunities.”\n\nD) Socio-demographics:\n\nThe socio-demographic measures collect essential personal and household information from respondents (incl. gender; age; years of formal education completed; parents’ education levels; marital status; employment status; average weekly and monthly disposable income; and household members).\n\nn/a\n\nThe study adhered to the Declaration of Helsinki and received approval from the Ethics Committee “Comissão De Ética E Deontologia Para A Investigação Científica (CEDIC)” of Lusófona University (Protocol code: CEDIC-2023-02-08; Approval Date: February 1, 2023). Before conducting the interviews, participants were informed about the general objective of the study and verbal consent was obtained. Verbal consent was deemed appropriate due to the data collection methodology, which involved telephone interviews.",
"appendix": "Data availability\n\nThe data presented are openly available at OSF repository https://osf.io: National survey on online gambling activities among young people in Portugal. (https://doi.org/ 10.17605/OSF.IO/JEK2T ) 13\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC B4.0).\n\n\nAcknowledgements\n\nn/a\n\n\nReferences\n\nTomei A, Petrovic G, Simon O: Offline and online gambling in a Swiss emerging-adult male population. J. Gambl. Stud. 2022; 38(4): 1215–1228. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWardle H, Degenhardt L, Ceschia A, et al.: The Lancet Public Health Commission on gambling. Lancet Public Health. 2021; 6(1): e2–e3. PubMed Abstract | Publisher Full Text\n\nAbarbanel B, Gainsbury SM, King D, et al.: Gambling games on social platforms: How do advertisements for social casino games target young adults? Policy Internet. 2017; 9(2): 184–209. Publisher Full Text\n\nChóliz M: The challenge of online gambling: the effect of legalization on the increase in online gambling addiction. J. Gambl. Stud. 2016; 32: 749–756. PubMed Abstract | Publisher Full Text\n\nMontiel I, Ortega-Barón J, Basterra-González A, et al.: Problematic online gambling among adolescents: A systematic review about prevalence and related measurement issues. J. Behav. Addict. 2021; 10(3): 566–586. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbarbanel B, Johnson MR: Gambling engagement mechanisms in Twitch live streaming. Int. Gambl. Stud. 2020; 20(3): 393–413. Publisher Full Text\n\nRomero W, Bologna E: Técnicas de muestreo.Bologna E, editor. Estadística para psicología y educación. 2013; pp. 269–297. Editorial Brujas.\n\nCanale N, Griffiths MD, Vieno A, et al.: Impact of Internet gambling on problem gambling among adolescents in Italy: Findings from a large-scale nationally representative survey. Comput. Hum. Behav. 2016; 57: 99–106. Publisher Full Text\n\nHubert PF: Jogadores patológicos online e offline: caracterização e comparação (Doctoral thesis). Universidade Autónoma de Lisboa; 2015. Reference Source\n\nHubert P: Perturbação ou abuso de jogo? Navegação à vista nos limites do diagnóstico.Calado V, Org. Jogo, Internet e Outros Comportamentos Aditivos – dossier temático. 2019; pp. 71–87. SICAD, Ministério da Saúde – Portugal. Reference Source\n\nNoble N, Freund M, Hill D, et al.: Exposure to gambling promotions and gambling behaviors in Australian secondary school students. Addict. Behav. Rep. 2022; 16: 100439. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWare J Jr, Kosinski M, Keller SD: A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med. Care. 1996; 34(3): 220–233. Publisher Full Text\n\nFarias AR, Antunes AC: National survey on online gambling activities among young people in Portugal.2024, June 6. Publisher Full Text"
}
|
[
{
"id": "332353",
"date": "31 Oct 2024",
"name": "Tiange Xu",
"expertise": [
"Reviewer Expertise Problem gambling"
],
"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 dataset on online gambling behaviors among Portuguese youth (18-34 years old), collected through telephone surveys with 1,993 participants.\nThe study aims to understand gambling prevalence, habits, behaviors, and their antecedents/consequences. The data was collected using CATI methodology with robust quality control measures.\nRationale for dataset creation: The authors clearly establish the importance of studying online gambling among youth, citing relevant statistics and highlighting the growing concerns around this issue.\nProtocols and Technical Soundness: While the overall methodology is sound, I have a few concerns: 1) Could you clarify how you handled non-response rates? What was considered an \"abnormal\" non-response rate? 2) The split into two sub-samples needs more explanation—what was the rationale behind this division?\nMethods and Materials for Replication: I appreciate the detailed description of the survey methodology, but a few elements are missing: 1) The coding plans mentioned for open-ended questions should be described; 2) Could you specify the software used for data analysis? 3) Please provide more details about the pilot phase—like, how many participants were involved, and what specific changes were made based on the pilot?\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and materials 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/13-893
|
https://f1000research.com/articles/13-891/v1
|
06 Aug 24
|
{
"type": "Case Report",
"title": "Case Report: The Sausage Technique using Anorganic Bovine Bone Mineral for Horizontal Bone Augmentation at the Crestal Part of a Posterior Mandibular Ridge: A Case Report.",
"authors": [
"Ali Ali",
"Mays Khazem",
"Zafin Karabeit",
"Mays Khazem",
"Zafin Karabeit"
],
"abstract": "Following tooth extraction, the alveolar bone goes through a natural remodeling process resulting in a significant bone resorption which may complicate dental implant placement without prior bone augmentation treatment. The sausage technique is a modified guided bone regeneration (GBR) method that has been successfully used for horizontal bone augmentation. This technique was developed to increase the bone growth at the alveolar crest. Although the sausage technique uses a combination of autograft chips and xenograft particles with a native collagen membrane, several studies have questioned whether adding autograft chips is essential for bone formation with guided bone regeneration. Moreover, harvesting the bone graft may increase the donor site morbidity and patient discomfort. This case report aimed to investigate the bone gain radiologically when the sausage technique was applied to treat a healthy, thirty-year-old patient with a horizontal defect in the posterior mandibular region using anorganic bovine bone mineral (ABBM) particles with Jason membrane, assess the implant primary stability in the augmented ridge, and present the surgical procedure steps in details. After nine months of healing, the cone-beam computed tomography (CBCT) revealed approximately 4.32 mm of bone gain at the alveolar crest in the buccal-lingual direction. The graft particles were well integrated into the newly formed bone. Two implants were inserted with an insertion torque of 35 N/cm. The ISQ values were 76 for the most anterior implant and 78 for the posterior implant. Within the limitations of this case report, the sausage technique using ABBM particles without autograft chips was an effective approach in achieving the prerequisite bone width at the crest in cases with horizontal bone defects.",
"keywords": [
"GBR",
"The sausage technique",
"Anorganic bovine bone mineral",
"Horizontal bone augmentation."
],
"content": "Introduction\n\nAlveolar Bone resorption is an inevitable consequence after tooth extraction1 as a result of the lack of mechanical load transmitted by the teeth to the bone.2 A noticeable reduction of the alveolar bone width has been observed within the first six months.3 However; the bone continues to resorb over time.3 The bony defects could be categorized as horizontal, vertical, or both. This may help clinicians to choose the proper treatment modality to manage the deficient ridge.4 The class IV alveolar bone atrophy according to the Cawood-Howell classification commonly referred to as the knife edge ridge represents a unique situation with an adequate height but a deficient width. In such cases, lateral bone augmentation is essential before dental implant placement.5 Guided bone regeneration (GBR) has been regarded as an authoritative approach for managing horizontal defects.6 The concept of GBR uses graft materials as a scaffold to preserve the created space and a non-resorbable or resorbable membrane to exclude the growth of epithelium and connective tissue cells inward the defect. The use of resorbable membranes in GBR is well documented, and its application has increased widely to overcome the risks and complications associated with non-resorbable membranes.7 Despite that, the conventional GBR using resorbable membranes did not obtain the desired bone growth at the alveolar crest due to the collapse of the resorbable membrane that forces the graft material to migrate apically.5 Therefore, Urban and colleagues proposed an improved technique to stabilize the graft material to the crest by modifying the collagen membrane fixation method.5 The original sausage technique combines autograft chips with anorganic bovine bone mineral (ABBM) particles to provide the graft mixture with osteogenic properties.6 Although autogenous graft is considered the gold standard of graft materials, harvesting the bone may increase the morbidity of the donor site and postoperative complications. Furthermore, autograft has a high resorption rate, which can reduce its ability to sustain space for an extended period.4,8 The ABBM is derived from xenogenous sources and treated with heat and chemical products to produce a human bone-like structure. The ABBM has a low resorption rate, serving only as a scaffold with a prolonged space-maintaining feature.9 Several authors deemed that GBR using ABBM is a reliable method to augment horizontal alveolar bone atrophy.4,10,11 Thus, the purpose of this case report was to scrutinize the effectiveness of the sausage technique using ABBM without autograft chips radiologically in increasing the bone width at the crestal part of a posterior mandibular knife edge ridge, report implants primary stability in the healed ridge when using such graft materials, and present a detailed description of the surgical technique.\n\n\nCase presentation\n\nA healthy, non-smoker, thirty-year-old, unemployed, female patient attended the oral and maxillofacial surgery department of the faculty of dentistry at Damascus University to address the issue of missing teeth in the right lower quadrant. A comprehensive clinical examination and dental history evaluation determined that the premolars and molars had been absent for 5 years due to extensive caries. The edentulous area exhibited a keratinized tissue of 3 mm (Figure 1). The CBCT (Pax-i3D Green; VATECH, Gyeonggi Province, South Korea) revealed a knife edge ridge in the edentulous area, which was insufficient for dental implant placement without prior horizontal bone augmentation. The buccal-lingual measure was performed on multiple CBCT sectional views 2 mm below the crest using Ez3D Plus 3D Viewer Ver. 1.2.6.33 (VATECH Co., South Korea) (Figure 2), and the average of the bone width was calculated (Table 1). A staged GBR using the sausage technique was proposed as a treatment plan to rebuild the ridge to receive dental implants after nine months of healing. Before starting the surgical procedure, the patient was instructed to rinse for 2 minutes with 0.12% chlorhexidine solution. Inferior alveolar nerve and buccal nerve block were administrated with 2% lidocaine and 1:100000 epinephrine (Lidocaine 2% E-100, New Stetic SA, Guarne, Colombia). The safety flap5 was reflected, including a mid-crestal, two vertical, and intrasulcular incisions. The mesial vertical incision was made two teeth away from the intended site at the mesiobuccal angle of the right lateral incisor, and the distal one was made by extending the crestal incision toward the anterior border of the ascending ramus. An additional 3-4 mm hokey stick-like vertical incision was made at the mesiolingual aspect of the right canine to aid in advancing the lingual flap. A periosteal elevator was used to reflect a full-thickness flap buccally and lingually to expose the deficient ridge. The lingual flap was advanced by separating the mylohyoid muscle attachments from the inner part of the lingual flap without separating them from the bone. A curette was used to clean the soft tissue debridement (Figure 3). Bone decortication was performed using a round surgical bur to procure blood supply to the graft particles (Figure 4). A porcine pericardium membrane (Jason® membrane; 20×30 mm; Botiss Biomaterials GmbH, Zossen, Germany) was secured to the lingual side using two titanium pins (titan pin set, botiss biomaterials GmbH, Zossen, Germany). The xenograft particles (Cerabone®; particles sized 1-2 mm; Botiss Biomaterials GmbH, Zossen, Germany) were hydrated with saline and packed into the defect at an appropriate volume (Figure 5). The membrane was then molded over the graft, affixed to the buccal bone with one pin distobuccally, stretched mesially to push the graft particles towards the ridge, and stabilized using another pin. The membrane margin was lifted at the area between the former buccal pins, filled with an additional quantity of graft particles that were pushed coronally toward the crest. lastly, the membrane was again stretched apically, and a final pin was placed between the two buccal pins (Figure 6). The periosteum on the buccal flap was scored, ensuring proper flap mobility for tension-free closure. The flaps were closed with a (4.0) Nylon suture, using horizontal and simple interrupted mattress sutures (Figure 7). The patient received a prescription for amoxicillin 500 mg, four times daily for seven days, ibuprofen 400 mg, three times daily for five days, and chlorhexidine 0.12% for rinsing, starting 24 hours post-operatively and lasting for ten days. The augmented site was evaluated after 3, 5, 7, and 10 days. The incisions healed normally without any complications. There was no wound dehiscence or membrane exposure and the sutures were removed on the tenth day after the procedure. Nine months later, another CBCT image was acquired, and the ridge was re-measured as described earlier (Figure 8). The bone gain outcome is shown in Table 1. In the second surgical procedure, a full-thickness flap was reflected, as previously described (Figure 9), the clinical appearance shows a thick periosteal lining the grafted ridge with more difficulty in raising the flap and good incorporation of the graft particles into the newly formed bone. The unincorporated graft particles were removed using a curette. Two implants sized 3.5×10 and 4×8.5 (AnyOne®; MegaGen implant, Daegu, Korea) were placed at the site of #44 and #46 respectively (Figure 10). Although the drilling protocol for implant placement was similar to that in pristine bone, the grafted ridge showed less resistance confronting the drills. The implant osteotomies were bleeding, revealing a living bone formation in the grafted site. There were no separation parts from the augmented ridge during drilling and the implants were placed with the handpiece and completed with the torque wrench. The insertion torque (using the torque wrench) and ISQ value (using MegaGen® ISQ device) were recorded (Table 2). The flap was closed with (4.0) silk sutures, utilizing interrupted sutures (Figure 11). The patient was prescribed the same medication regimen as after the first surgical procedure, and the sutures were removed after a week. Despite the high ISQ value for both implants, the author prefers to place cover screws and follow the delayed loading protocol.\n\nThe bone growth can be noted.\n\nThe graft material, Jason membrane, and titanium pins are kindly provided by Botiss Biomaterials GmbH (Zossen, Germany).\n\n\nDiscussion\n\nThe sausage technique enhances graft stability and prevents the collapse of the resorbable membrane. Urban and colleagues used a composite graft material consisting of autograft chips and ABBM particles in a ratio of 1:1 and they suggested examining the effectiveness of different bone substitutes with this technique.5 Bovine bone promotes bone formation by osteoconductive characteristics, providing a mechanical scaffold that maintains the created space and facilitates the migration and occupation of bone regeneration cells to form new bone.9 Long-term stability, decreased morbidity, and surgical complications are the main advantages of using xenograft bone.4 Jason membrane is a native collagen membrane derived from porcine pericardium with a slow degradation due to its natural cross-linked collagen fibers. It has a superior tear resistance property.12 The measurements of this report were conducted on the cone beam sectional view 2mm below the top of the crest and the average width was 3.58 mm and 7.9 mm before the treatment and after nine months of healing respectively with a horizontal bone gain of approximately 4.32 mm which was similar to the outcome found in a systematic review in which the bone gain was 4.4 mm in the horizontal direction when using xenograft particles with or without autogenous graft.4 Urban13 proposed that the sausage technique combining autograft and ABBM is more predictable in securing the graft on the crestal part of the alveolar ridge than the classic pouch technique. Nevertheless, a bone gain of 5.68 mm was obtained utilizing both techniques mentioned earlier in cases with horizontal defects.13 In a preclinical study in dogs, song and colleagues10 highlighted that there was no additional advantage in bone formation from adding autogenous chips to xenograft particles in treating horizontal defects. Even though all the ridges restored their original form, the bone formation was restricted beyond the ridge contour.10 Therefore, in the author’s perspective, Urban obtained greater bone gain due to using a larger membrane thus further graft materials were packed into the defect. It may be suggested that a large-sized membrane should be utilized with long defects. Steigmann,14 Amoian and colleagues15 as well as Hammerle and colleagues16 recorded 3.0364 mm, 3.37 mm, and 3.7 mm of bone gain respectively when using the classic GBR with particulate xenograft without autograft to augment deficient ridges in the horizontal direction. The superior result of this report could be elucidated by using the sausage technique rather than the classic GBR. In a study conducted by Mendoza-Azpurthe and colleagues,11 the average bone gain was 5.6 ± 1.35 mm when using xenograft particles and collagen membranes, it is worth mentioning that Mendoza-Azpurthe and colleagues11 measured the buccal-palatal width 5,7, and 11 mm below the crest using the CBCT,11 whereas the current report measurement was conducted 2mm apical to the top of the ridge. It was established that the greatest bone growth was gained apical to the crest as a result of the inability of the resorbable membrane to withstand at the crest and the apical relocation of the graft particles.5 Primary closure of the incisions, angiogenesis, stability of the graft particles, and blood clot, in addition to sustaining the created space in which bone will form, are the fundamental principles for accomplishing successful GBR.5 Thus without a proper membrane fixation, the stability and space maintained will be compromised resulting in poor bone growth outcomes at the crest.5 The sausage technique is a cumulative learning procedure with several critical steps to be aware of.5,13 To the best of the author’s understanding, the final push of the graft particles toward the crest, stretching the membrane apically, and fixing with a pin or two between the distal-buccal and mesial-buccal pins are the most critical steps in this technique to achieve a stable and firmly fixed graft-membrane complex. This report’s main limitation was the absence of a histological study to define the bone structure at the augmented ridge. Nonetheless, earlier studies found a formation of new and organized bone between the graft particles similar to that in pristine bone.10,8,15 It is worth noting that the present report focused on the surgical phase and the horizontal bone growth outcome without considering the prosthetic phase after implant placement which represents another limitation. Further studies are encouraged with a controlled randomized clinical trial design to confirm the data of the bone gain with the sausage technique using ABBM and a collagen membrane in treating horizontal alveolar bone defects. In addition, comparative researches are highly required to assess the insertion torque and primary stability of the implants in the augmented ridges and their influence on the osseointegration of the implants and loading protocols.\n\nWithin the limitations of this case report, it could be concluded that the sausage technique using ABBM particles without autograft chips showed a great capability to maintain the created space, prevent the collapse of the collagen membrane, and acquire an adequate width at the crestal part of the alveolar bone.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and images was obtained from the patient.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nKhojasteh A, et al.: Guided Bone Regeneration for the Reconstruction of Alveolar Bone Defects. Ann. Maxillofac. Surg. 2017; 7(2): 263–277. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHansson S, Halldin A: Alveolar ridge resorption after tooth extraction: A consequence of a fundamental principle of bone physiology. J. Dent. Biomech. 2012; 3: 1758736012456543. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGirish Kumar N, et al.: To assess the efficacy of socket plug technique using platelet rich fibrin with or without the use of bone substitute in alveolar ridge preservation: a prospective randomised controlled study. Oral Maxillofac. Surg. 2018; 22(2): 135–142. PubMed Abstract | Publisher Full Text\n\nde Azambuja Carvalho PH, et al.: Horizontal ridge augmentation using xenogenous bone graft-systematic review. Oral Maxillofac. Surg. 2019; 23(3): 271–279. PubMed Abstract | Publisher Full Text\n\nUrban IA, Monje A: Guided Bone Regeneration in Alveolar Bone Reconstruction. Oral Maxillofac. Surg. Clin. North Am. 2019; 31(2): 331–338. PubMed Abstract | Publisher Full Text\n\nUrban IA, et al.: Horizontal ridge augmentation with a collagen membrane and a combination of particulated autogenous bone and anorganic bovine bone-derived mineral: a prospective case series in 25 patients. Int. J. Periodontics Restorative Dent. 2013; 33(3): 299–307. PubMed Abstract | Publisher Full Text\n\nWessing B, et al.: Guided Bone Regeneration with Collagen Membranes and Particulate Graft Materials: A Systematic Review and Meta-Analysis. Int. J. Oral Maxillofac. Implants. 2018; 33(1): 87–100. PubMed Abstract | Publisher Full Text\n\nMello BF, et al.: Horizontal Ridge Augmentation Using a Xenograft Bone Substitute for Implant-Supported Fixed Rehabilitation: A Case Report with Four Years of Follow-Up. Case Rep. Dent. 14 May. 2020; 2020: 6723936–6723938. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao R, et al.: Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments. Molecules (Basel, Switzerland). 18 May. 2021; 26(10): 3007. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSong YW, et al.: Addition of autogenous bone chips to deproteinized bovine bone mineral does not have additional benefit in lateral ridge augmentation-A preclinical in vivo experimental study. Clin. Oral Implants Res. 2021; 32(9): 1105–1114. PubMed Abstract | Publisher Full Text\n\nMendoza-Azpur G, et al.: Horizontal ridge augmentation with guided bone regeneration using particulate xenogenic bone substitutes with or without autogenous block grafts: A randomized controlled trial. Clin. Implant. Dent. Relat. Res. 2019; 21(4): 521–530. PubMed Abstract | Publisher Full Text\n\nRen Y, et al.: Barrier Membranes for Guided Bone Regeneration (GBR): A Focus on Recent Advances in Collagen Membranes. Int. J. Mol. Sci. 29 Nov. 2022; 23(23): 14987. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUrban I: Vertical and Horizontal Ridge Augmentation New Perspectives. 1st ed.Quintessence Publishing; 2017.\n\nSteigmann M: Pericardium membrane and xenograft particulate grafting materials for horizontal alveolar ridge defects. Implant. Dent. 2006; 15(2): 186–191. PubMed Abstract | Publisher Full Text\n\nAmoian B, et al.: A histologic, histomorphometric, and radiographic comparison between two complexes of CenoBoen/CenoMembrane and Bio-Oss/Bio-Gide in lateral ridge augmentation: A clinical trial. Dent. Res. J. 2016; 13(5): 446–453. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHämmerle CHF, et al.: Ridge augmentation by applying bioresorbable membranes and deproteinized bovine bone mineral: a report of twelve consecutive cases. Clin. Oral Implants Res. 2008; 19(1): 19–25. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "356083",
"date": "17 Jan 2025",
"name": "Rajinder K. Sharma",
"expertise": [
"Reviewer Expertise periodontitis",
"periodontal medicine",
"health behavior."
],
"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 case report is about horizontal bone augmentation through staged GBR using the sausage technique to facilitate implant placement. Please consider the following points to improve the quality of discussion section. 1. How the surgical procedure is different from the procedure proposed by Istvan Urban and colleagues, except the exclusion of autogenous graft. 2. What are the alternatives to bone augmentation to facilitate implant placement in this case. Please describe briefly the merits and limitations. 3. What are the probable outcomes of attempted bone augmentation in this case? And how the bone augmentation was ascertained? 4. What are the long-term complications associated with fragmented bone graft materials? 5. Is the procedure described in this case relevant for improving the success of implant placement? 6.Ethical considerations for use of materials with animal origin.\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? No\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-891
|
https://f1000research.com/articles/13-256/v1
|
08 Apr 24
|
{
"type": "Brief Report",
"title": "Community preparedness for earthquake disasters: A preliminary assessment of awareness and disaster infrastructure response in Cianjur, West Java-Indonesia",
"authors": [
"Dewayany Sutrisno",
"Yatin Suwarno",
"Ati Rahadiati",
"Muhammad Iqbal Habibie",
"Prabu Kresna Putra",
"Hari Prayogi",
"Amien Widodo",
"Fathia Zulfati Sabrina",
"Ahmad Kosasih",
"Yatin Suwarno",
"Ati Rahadiati",
"Muhammad Iqbal Habibie",
"Prabu Kresna Putra",
"Hari Prayogi",
"Amien Widodo",
"Fathia Zulfati Sabrina",
"Ahmad Kosasih"
],
"abstract": "Background The danger of earthquakes poses a serious threat to people worldwide. One of the most significant challenges is preparing communities to cope effectively with this disaster. Therefore, understanding earthquake hazards is critically important for preparedness, mitigation, and an effective response to this threat. This report aims to observe and conduct a preliminary assessment of the degree to which community preparedness for earthquake disasters has been implemented.\n\nMethods Empirical data were obtained from survey respondents and interviews. The respondents were members of a community affected by the Cianjur earthquake, which occurred on November 21, 2022. The data were analysed using the mean range approach, based on Likert scales. Additionally, the Spearman correlation method was employed to indicate the relationship between community awareness and infrastructure readiness.\n\nResult Based on empirical evidence and preliminary analysis, it is evident that the preparedness of the community to respond effectively to earthquake catastrophes is inadequate. An apparent lack of readiness is observed in the inadequate construction of housing that fails to meet disaster standards, and the absence of disaster response facilities is notable.\n\nConclusions Based on our initial assumption, it appears that knowledge related to disaster resilience in this area has not been adequately disseminated or socialized. However, this premise requires further investigation.",
"keywords": [
"Earthquake",
"community awareness",
"respondent’s survey",
"earthquake-resistant houses",
"Cianjur",
"Indonesia",
"disaster response",
"infrastructure"
],
"content": "Introduction\n\nThe implementation of earthquake disaster risk reduction activities involving communities presents formidable challenges in numerous countries (Hosseini et al., 2014). Hence, implementing disaster preparedness measures is imperative for populations living in locations prone to earthquake hazards. However, ensuring earthquake safety cannot be guaranteed unless every member of the community possesses an in-depth awareness of the ramifications of earthquakes and has the knowledge to handle such situations (Siawsh et al., 2023). Indonesia, renowned for its high incidence of seismic activity worldwide scale (Parwanto and Oyama, 2014), bears significant responsibility in the realm of earthquake prevention and mitigation. Consequently, evaluating community knowledge pertaining to earthquake hazards is a pivotal measure in the establishment of efficient policies for disaster preparedness and mitigation.\n\nThis report aims to observe and conduct a preliminary assessment of the degree to which community preparedness for earthquake disasters has been implemented. The report focuses on the community’s awareness of earthquake disasters and their relationship with the preparedness of the environment in which they reside, including housing and disaster response facilities. The earthquake discussed in this report was the Cianjur earthquake that occurred in West Java, Indonesia (Figure 1). This seismic event took place on November 21st, 2022, with a magnitude of 5.6 (Supendi et al., 2023). The seismic event was characterized as a shallow or near-surface earthquake, and its destructive potential was not necessarily contingent on its magnitude. Instead, the seismic event not only resulted in the destruction of various structures, residences, and public facilities but also tragically led to the loss of at least 334 lives, injuries to 583 individuals, and the sudden displacement of 114,683 individuals who found themselves in a state of destitution (BNPB, 2022; Antara news, 2022).\n\nNote: The red outlined area represents the most affected area, indicates the survey location\n\nAfter a period of ten months following the occurrence, it is evident that the resolution of social issues and infrastructure difficulties remains incomplete. Many individuals continue to reside in temporary shelters including emergency tents and improvised educational facilities. The government has implemented housing initiatives to accommodate those living in regions affected by earthquakes, which are characterized by significant devastation. The extent of the success of this initiative will also be a part of this observation, as it is a crucial component of infrastructure disaster awareness.\n\n\nMethods\n\nIn this report, the hypothesis to be addressed is the level of disaster awareness and its influence on disaster preparedness infrastructure. Therefore, community awareness was investigated through respondent surveys and interviews.\n\nThe survey was conducted by disseminating questionnaires to residents in earthquake-affected areas, while interviews were exclusively conducted with officials from the four most severely impacted sub-districts, namely Rancagoong, Nagrak, Cibeureum, and Ciputri (Figure 1). These sub-districts were identified as the most severely impacted by the Meteorology, Climatology, and Geophysical Agency (BMKG) in 2022. Both surveys and interviews were using the exact same sets of questions, and the results are processed in the same database and repository. The quantification of survey and interview participants is outlined in the subsequent subsection.\n\nThe steps of its implementation are as follows:\n\nThe eligibility criteria for respondents include individuals residing in areas directly impacted by earthquake disasters, aged at least 20 years, proficient in the Indonesian language, from diverse professional backgrounds spanning from farmers to office workers, possessing a minimum educational level of high school, and willing and capable of participating as respondents in this research project.\n\nWe employed a normal distribution algorithm to calculate the appropriate number of respondents, based on their respective proportions within the total population. We used 95% confidence level and a margin of error of 0.10. The algorithm is described as follows.\n\nWith the numbers of population being 500, the minimum number of respondents based on this calculation was 97.\n\nBefore conducting the survey, ethical considerations regarding the participants were carried out. All participants were fully briefed about the purpose and nature of the research, including the assurance of confidentiality. Prior to conducting the surveys, informed consent was obtained from both the respondents and interview participants. This was accomplished by providing them with the option to either check a box or sign their assent on the first page of the questionnaire, which was utilized for both surveys and interviews.\n\nFor ethics approval, our institution requires that all decisions be formally sanctioned. The study has obtained ethical clearance approval under the reference Number 353/KE.01/SK/06/2023, issued on June 5, 2023, by the National Research and Innovation Agency of the Republic of Indonesia. Indeed, the authors have agreed to questionnaire’s content.\n\nThe survey and interview were based on three categories: individual’s awareness, building construction awareness, and disaster facilities and infrastructure. These categories were meticulously outlined in a questionnaire that employed uniform content and structure across both survey respondents and interview participants. The data collection was conducted from July 11th to July 13th, 2023, in the most earthquake-affected area of Cianjur Regency (see Figure 1). The questionnaire was disseminated to the community by village officials within the earthquake-affected areas, and the gathered responses were then returned to us by the village officials. Concurrently, the process of data collection for interviews was conducted face-to-face with the officials of the four affected sub-districts, i.e., Rancagoong, Nagrak, Cibeureum, and Ciputri. The questions are:\n\nIndividual’s awareness\n\n• Knowing you live in a seismically active location\n\n• Understanding earthquake risk, including residence collapse and landslides\n\n• Understanding the safely evacuate during an earthquake\n\n• Having an earthquake emergency plan for the family\n\n• Conversant with earthquake mitigation measures such as increasing awareness of potential household hazards, improving home conditions and emergency communication\n\n• Have attended earthquake disaster awareness training or programs\n\n• Monitoring earthquake information and warnings from credible sources\n\nBuilding criteria awareness\n\n• The destruction of residential structures resulting from seismic activity.\n\n• Type of houses\n\n• House typology in seismic context\n\n• Acknowledge earthquake-resistant housing criteria\n\n• Willingness to build earthquake resistant houses\n\n• Knowledge of earthquake-resistant housing design and reconstruction utilizing local material\n\n• Willingness to relocate if the previous location cannot be rebuilt.\n\nDisaster’s facilities and infrastructure\n\n• Muster points\n\n• Evacuation zone\n\n• Shelter\n\n• healthcare facilities\n\n• emergency response center\n\n• Disaster information facilities.\n\n• Communities self-manage disaster facilities and infrastructure.\n\nFor the data analysis process, we used Microsoft Excel software from Office 2020. We utilized the following weighting scoring method:\n\nAs a new development, we transformed the weighted score value onto a Likert-4 scale utilizing the following formula:\n\nWe then modified the concept of Dacanay et al. (2018) to determine the community’s level of earthquake awareness and evaluate risk reduction infrastructure awareness (Table 1).\n\nLevel of awareness (modified from Dacanay et al., 2018).\n\nTo assess the correlation between disaster awareness and disaster preparedness infrastructure (houses and facilities), we used the Spearman’s correlation algorithm (Spearman, 1904), there is:\n\nVariable n represents the total number of data points, and t denotes the count of duplicate numbers.\n\nA correlation coefficient > rtable0.05indicates a positive relationship between the variables. A significance level of 0.05 is employed as a statistical tool to ascertain the statistical significance of the Spearman correlation coefficient (r) between two variables within a dataset (Zar, 1972).\n\nThe questionnaire was also subjected to validation and reliability testing using Cronbach’s alpha. If the calculated value of r was greater than 0.7, it was considered valid. The majority of validity values were > 0.7, indicating that it is valid, while the reliability value was 0.942, indicating that it is reliable (Sutrisno, 2023).\n\n\nResults\n\nThe field survey data and its corresponding weighting can be seen on Open Science Framework (Sutrisno, 2023).\n\nThe results of the data revealed that the majority of the community possessed a limited understanding of earthquake disasters and their impacts (Table 2). This is indicated by issues related to knowing that they live in a seismically active location, understanding earthquake risk, knowing how to safely evacuate during an earthquake, monitoring earthquake information and warnings from credible sources, having an earthquake emergency plan for their family, being conversant with earthquake mitigation measures, and attending earthquake disaster awareness training.\n\nRespondents’ level of awareness on earthquake.\n\nWe observed that a substantial number of participants exhibited a limited level of awareness regarding earthquake-resistant structures. Nevertheless, there exists a significant inclination towards constructing houses that can withstand earthquakes, which conflicts with the reluctance to relocate while inhabiting a region susceptible to earthquake hazards.\n\nThe Spearman analysis results demonstrated a correlation between the lack of awareness of earthquake disasters and the condition of settlements and readiness of infrastructure in their residential areas. The aforementioned calculations yield a Spearman coefficient of rxy = 0.978 for the level of awareness pertaining to earthquake-resistant structures and a coefficient of rxy = 0.962 for the level of preparation for disaster response facilities. The rtable0.05for a confidence level of 0.05, Spearman’s rank is 0.714. In this case, the of rxy > rtable0.05; thus, it can be observed that there is a strong correlation between disaster awareness and earthquake-resistant houses and limitations in completing disaster resilience facilities.\n\nA lack of public awareness of earthquake disasters and the condition of the buildings in which they reside can also be observed at the level of building damage, as shown in Figure 2.\n\nThe results show that only 16% of the houses remained undamaged, while the rest experienced damage ranging from minor (31%), moderate (24%), to severe (29%) (Figure 2). The observed phenomenon can be ascribed to the inherent heterogeneity in the construction quality of buildings with regard to their capacity to satisfy the earthquake-resistant criteria.\n\n\nDiscussion\n\nThe results mentioned above indicate a positive association between the population’s inadequate knowledge of earthquake hazards and standards of earthquake-resistant housing and disaster response facilities. We also see two possibilities related to our previous findings: knowledge related to disaster resilience in this area has not been well disseminated or socialized, or they are unaware that they reside in earthquake-prone locations. This is evidenced by several issues such as the absence of sufficient planning for mitigating disasters, insufficient public education on appropriate measures to be performed during earthquakes, limitations in comprehending and equipping disaster resilience infrastructure, and a lack of understanding related to earthquake-resistant housing. Understanding earthquake infrastructure is crucial because the fatalities of earthquakes are commonly caused by building collapse (Markušic et al., 2020).\n\nThe period of 10 months following the catastrophe has proven to be a significant educational opportunity for all individuals involved. The government has initiated the process of providing guidance to the community to facilitate the reconstruction of their homes in alignment with the prescribed criteria (World Bank, 2021; BSN, 2019). This was demonstrated by the level of public awareness of the construction of earthquake-resistant housing, particularly in light of the accessibility of financial assistance and the provision of guidance by the local housing authority. Regrettably, the provision of aid is not accompanied by educational initiatives pertaining to disaster preparedness or building infrastructure for disaster response.\n\nA limitation of this study was the absence of in-depth interviews regarding sociocultural issues. Disaster-affected areas are characterized by features of agricultural and mountainous tourism. We assume that an agrarian society’s strong attachment to farming practices contributes to their reluctance to relocate far from agricultural land. The potential impact of tourism on the limited availability of traditional Sundanesse wooden houses in this area is also considered. These wooden houses were designed to withstand local natural phenomena and exhibit earthquake resistance (Dutu, 2021). Another limitation is that socio-culture is a periodic public awareness campaign, the provision of training programs for disaster preparation, the incorporation of earthquake education into the school curriculum, and the active involvement of local populations in disaster simulations and drills. We believe that these aspects require further research.",
"appendix": "Data availability\n\nOpen Science Framework: https://doi.org/10.17605/OSF.IO/UJ68Z (Sutrisno, 2023).\n\nThe project contains the following underlying data:\n\n- Recapitulation of surveys_rw.csv (Raw data from questionnaire and interviews)\n\n- Matrix of Scored Analysis.csv (Analysed data)\n\n- Reability Test_analysis.csv (Analysed data)\n\n- Validity Test_analysis.csv (Analysed data)\n\nOpen Science Framework: https://doi.org/10.17605/OSF.IO/UJ68Z (Sutrisno, 2023).\n\nThe project contains the following extended data:\n\n- Quisitionnaire_CC awarness2023.pdf (Questionnaire)\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 express our gratitude to the National Research and Innovation Agency (BRIN), Education Fund Management Agency (LPDP), National Agency for Disaster Management (BNPB) and stakeholders at the disaster site in Cianjur Regency who assisted in conducting the survey.\n\n\nReferences\n\nAntara news: Gempa-cianjur-korban-meninggal-bertambah-menjadi-334-orang.2022. Accessed 3 December 2022. Reference Source\n\nBNPB: [UPDATE]. 327 Orang Meninggal Dunia Pasca Gempa Cianjur.2022. Accessed 7 July 2023. Reference Source\n\nBSN (Badan Standarisasi Nasional). Standar Nasional Indonesia (SNI 1726): Tata cara perencanaan ketahanan gempa untuk struktur bangunan gedung dan nongedung. Jakarta: BSN; 2019.\n\nDacanay JM, Mauro MGB, Sandoval JA, et al.: Community awareness on earthquake and assessment on earthquake risk reduction practices in a Philippine municipality. Int. J. Appl. Sci. 2018; 1(2):77–83. Publisher Full Text\n\nDutu: Chapter 14 - An engineering view of traditional timber frames with infills in Romania. Masonry Construction in Active Seismic Regions Woodhead Publishing Series in Civil and Structural Engineering.2021; 2021: 277–420. Publisher Full Text\n\nHosseini KAKA, Hosseini M, Izadkhah YO, et al.: Main challenges on community-based approaches in earthquake risk reduction: Case study of Tehran, Iran. Int. J. Disaster Risk Reduct. 2014; 8: 114–124. Publisher Full Text\n\nMarkušic S, Stanko D, Korbar T, et al.: The Zagreb (Croatia) M5.5 earthquake on 22 March 2020. Geosciences. 2020; 10(7): 252. Publisher Full Text\n\nParwanto NB, Oyama T: Statistical analysis and comparison of historical earthquakes and tsunami disasters in Japan and Indonesia. Int. J. Disaster Risk Reduct. 2014; 7: 122–141. Publisher Full Text\n\nSiawsh N, Peszynski K, Vo-Tran H, et al.: Toward the creation of disaster-resilient communities: The Machizukuri initiative – The 2011 Tōhoku Great East Japan Earthquake and Tsunami. Int. J. Disaster Risk Reduct. 2023; 96: 103961. Publisher Full Text\n\nSupendi P, Winder T, Rawlinson N, et al.: A conjugate fault was revealed by the destructive Mw 5.6 (November 21, 2022) Cianjur earthquake, West Java, Indonesia. J. Asian Earth Sci. 2023; 257: 105830. Publisher Full Text\n\nSpearman C: Proof and measurement of the association between two things. Am. J. Psychol. 1904; 15(1): 72–101. Publisher Full Text\n\nSutrisno D: Community perception on disasters. [Dataset]. Open Science Framework. 2023. Publisher Full Text\n\nWorld Bank: Building Indonesia’s Resilience to Disaster: Experiences from Mainstreaming Disaster Risk Reduction in Indonesia Program. A report for the implementation of P122240 – Mainstreaming Disaster Risk Reduction in Indonesia Phase II Programmatic Advisory Services Analytics. Jakarta: World Bank; 2021. Reference Source\n\nZar JH: Significance Testing of the Spearman Rank Correlation Coefficient. J. Am. Stat. Assoc. 1972; 67(339):578–580. Publisher Full Text"
}
|
[
{
"id": "297088",
"date": "04 Jul 2024",
"name": "Ayse Nuray Karanci",
"expertise": [
"Reviewer Expertise Disaster prepaparedness"
],
"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\nAlthough this is an interesting study of a population exposed to a recent earthquake there are important weaknesses in the manuscript. These are as follows: Introduction: Concept of awareness not only on earthquake hazards but also on adaptive behaviors needs to be discussed. There are numerous theoretical models linking awareness to adaptive behaviors. The introduction fails to discuss these theories. The terms used like disaster preparedness infrastructure needs to be specified. The hypothesis of the study needs to be more clearly given.\nMethod: This section needs to be organized as sample (for the questionnaire and interviews) Instruments used and procedure. Sample : Number of participants, the sociodemographic characteristics of the survey and interview participants need to be given in a table (age gender education etc.) Participants: Minimum of high school education was chosen. The authors need to explain the reason behind this. Survey instrument: Information on how it was developed the response format for the questions and the time frame to which the questions address, and the psychometric properties like Cronbach alpha values needs to be given. Procedure: For data collection needs to be given. The authors have done some interviews but no information is given on the results and the procedure. Results: Due to a lack of specific hypothesis the results and the analysis does not seem clear. A multiple regression analysis for adaptive behavior predictors may make the results more comprehensible. Discussion: Needs to be extended after considering all the above points. As it stands it is not clear how the authors reached these conclusions and their recommendations .\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? Partly\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": "12062",
"date": "05 Aug 2024",
"name": "Dewayany Sutrisno",
"role": "Author Response",
"response": "Author Response to THE REVIEWER - Reviewer Comment: -------------------------------- Although this is an interesting study of a population exposed to a recent earthquake there are important weaknesses in the manuscript. These are as follows: Introduction: Concept of awareness not only on earthquake hazards but also on adaptive behaviors needs to be discussed. There are numerous theoretical models linking awareness to adaptive behaviors. The introduction fails to discuss these theories. -------------------------------- Author Response: Thank you for your feedback. Indeed, there are some sentences in this paper that may have led to misunderstandings. This paper is part of a study aimed at understanding community perceptions regarding earthquake-resistant houses promoted by the Indonesian government, by considering that casualties from earthquakes are generally caused by building collapses. It is indicated by the title, “Community preparedness for earthquake disasters: A preliminary assessment of awareness and disaster infrastructure response in Cianjur, West Java-Indonesia\". We apologize, but in this paper, we focus more on raising community awareness about living in earthquake-prone areas, as well as the need for understanding earthquake-resistant houses and related infrastructure as part of community preparedness. Therefore, we did not conduct research related to community adaptability, as this would be more aligned with studies on community resilience. Regarding earthquake-resistant buildings, their ancestors had local wisdom by constructing traditional wooden houses in response to disaster-related concerns. However, the modernization of housing has altered the community's patterns, leading to limited knowledge about earthquake-resistant housing and other disaster preparedness facilities. This is a common issue in various earthquake-prone villages in Indonesia. Following your feedback, the revisions can be seen in the Introduction, paragraphs 1 and 3.\" “ …….Consequently, evaluating community knowledge pertaining to earthquake hazards is a pivotal measure in the establishment of efficient policies for disaster preparedness and mitigation, such as the awareness of living on the earthquake prone area, earthquake-resistant housing and its related infrastructures” and …..” The extent of the success of this initiative will also be a part of this observation, as it is a crucial component of infrastructure disaster awareness. Since most of the casualties in an earthquake have been determined to be deaths caused by buildings collapsing (Sutrisno et al, 2024)…” Reviewer Comment: -------------------------------- The terms used like disaster preparedness infrastructure needs to be specified. -------------------------------- Author Response: Thank you for your feedback. The term 'disaster preparedness infrastructure' that we refer to is specified as Earthquake-Resistant Buildings: Structures designed to withstand the shocks and damage caused by earthquakes. Evacuation Facilities: Safe and organized locations for evacuating residents during disasters, including evacuation routes and temporary shelters disaster facilities: such as health care facilities and emergency respond center. Training and Education: Programs that train and educate the community on how to respond correctly and effectively to disasters See the Sub chapter of instruments used and the questionnaire And the last paragraph of the introduction “….The disaster infrastructure referred to in this article includes buildings, particularly earthquake-resistant houses, as well as evacuation facilities such as evacuation roads, muster points, health facilities, and community training programs.” Reviewer Comment: -------------------------------- The hypothesis of the study needs to be more clearly given. -------------------------------- Author Response: The hypothesis to be tested in this study is that the level of disaster awareness has a significant influence on disaster preparedness infrastructure. To clarify, the details of this hypothesis are as follows: Level of Disaster Awareness: This refers to the extent to which individuals or communities understand and recognize the risks and hazards associated with earthquakes in their living environment. Disaster Preparedness Infrastructure: This encompasses all facilities, systems, and equipment prepared to deal with disasters, including earthquake-resistant buildings, early warning systems, evacuation facilities, emergency supply storage, and community training programs. This hypothesis posits that the higher the level of disaster awareness in a community, the better and more comprehensive the available disaster preparedness infrastructure. Reviewer Comment: -------------------------------- Method: This section needs to be organized as sample (for the questionnaire and interviews) Instruments used and procedure. Sample : Number of participants, the sociodemographic characteristics of the survey and interview participants need to be given in a table (age gender education etc.) -------------------------------- Author Response: Thank you for your feedback. We have restructured the methodology, as can be seen in the Methods chapter of this paper. In accordance with the reviewers’ suggestions, this section is divided into three subsections: samples, instruments used, and procedures. Regarding the data, the tables can be accessed by clicking the link provided in the Data Availability chapter of this paper (Repository Data). Reviewer Comment: -------------------------------- Participants: Minimum of high school education was chosen. The authors need to explain the reason behind this. -------------------------------- Author Response: Thank you for your feedback. Some word is missing, which we have corrected in the samples sub-chapter. “……..The eligibility criteria for respondents include individuals residing in areas directly impacted by earthquake disasters, aged at least 20 years, proficient in the Indonesian language, from diverse professional backgrounds spanning from farmers to office workers, possessing a minimum educational level of high school for village’s officials and any level of educations for respondents, and willing and capable of participating as respondents in this research project….” Reviewer Comment: -------------------------------- Survey instrument: Information on how it was developed the response format for the questions and the time frame to which the questions address, and the psychometric properties like Cronbach alpha values needs to be given. -------------------------------- Author Response: Thank you for your feedback. The methodology has been restructured according to the reviewers' suggestions. Development of Response Format: The response format for the questions was developed based on a literature review and discussions with experts in the field. We used a 4-point Likert scale to measure respondents' readiness for earthquake disasters. The questions in the questionnaire were designed to cover the respondents' experiences and knowledge from the period before the disaster up to ten months after the disaster. This was done to ensure that the data collected is relevant and current. To measure the internal consistency of the questionnaire, we calculated Cronbach's alpha values for each section of the questionnaire, aiming for values > 0.7 to establish validity. These values indicate that the questionnaire has good internal consistency and is reliable for measuring the intended research objectives. Reviewer Comment: -------------------------------- Procedure: For data collection needs to be given. The authors have done some interviews but no information is given on the results and the procedure. -------------------------------- Author Response: Thank you for the feedback. The interviews used the same format as the respondent survey. We have made corrections in the data collection subsection “…..Concurrently, the process of data collection for interviews was conducted face-to-face with the officials of the four affected sub-districts, i.e., Rancagoong, Nagrak, Cibeureum, and Ciputri. As previously explained in the Ethics Clearance chapter, the research background was first explained, followed by obtaining consent to participate, and then proceeding with the interview process…” Reviewer Comment: -------------------------------- Results: Due to a lack of specific hypothesis the results and the analysis does not seem clear. A multiple regression analysis for adaptive behavior predictors may make the results more comprehensible. -------------------------------- Author Response: Thank you for your feedback. We recognize that the lack of specific hypotheses can make the results and analysis appear unclear. As we mentioned earlier, this research focuses on community preparedness for earthquake disasters, specifically to assess awareness of living in the prone zone, the importance of earthquake-resistant houses and its supporting infrastructure. Therefore, we did not conduct an analysis of adaptive behaviour. Reviewer Comment: -------------------------------- Discussion: Needs to be extended after considering all the above points. As it stands it is not clear how the authors reached these conclusions and their recommendations. -------------------------------- Author Response: Thank you for your feedback. We have completed and revised it according to the objectives of this research."
}
]
}
] | 1
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https://f1000research.com/articles/13-256
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https://f1000research.com/articles/13-886/v1
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05 Aug 24
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{
"type": "Research Article",
"title": "All-cause mortality according to COVID-19 vaccination status: An analysis of the UK office for National statistics public data",
"authors": [
"Marco Alessandria",
"Giovanni Malatesta",
"Giovanni Di Palmo",
"Marco Cosentino",
"Alberto Donzelli",
"Marco Alessandria",
"Giovanni Malatesta",
"Giovanni Di Palmo",
"Marco Cosentino"
],
"abstract": "Background The mass vaccination campaign against COVID-19 has been commonly considered the best response to the global COVID-19 pandemic crisis. However, to assess its real-world overall effects, the best way can be the analysis of all-cause mortality by vaccination status. The UK is perhaps the only country which has made publicly available all-cause mortality data by vaccination status.\n\nMethods Data from April 2021 to May 2023 published by the UK Office for National Statistics (ONS) were retrospectively analyzed by age groups and vaccination status; the standardized mortality ratio (SMR) for all-cause and non-COVID-19 mortality was calculated against the corresponding unvaccinated groups.\n\nResults We found that across all age groups, all-cause mortality SMRs increased from a certain date, dependent on the age group. Across all age groups, all-cause mortality SMRs were initially much lower than 1. However, due to their increase, by a certain date for the 18-39, 80-89 and 90+ age groups they exceeded the reference value. For the other age groups, the date at which the SMR would reach 1 can be predicted, provided the trend is maintained. Non-COVID-19 SMRs’ trends were very similar. Their initial values much lower than 1 are suggestive of significant biases in the ONS dataset, leading to underestimate the risks for the vaccinated people, as it is implausible that COVID-19 vaccines protect against non-COVID-19 deaths.\n\nConclusions The increase over time in all-cause death SMRs in vaccinated people compared to unvaccinated, and their excess from the reference values for certain age groups, should be carefully considered to understand the underlying factors. It would be desirable for other major countries to systematically collect all-cause mortality by vaccination status and, in the meantime, a moratorium on promoting mass vaccination campaigns should be implemented.",
"keywords": [
"COVID-19",
"COVID-19 vaccinations",
"all-cause mortality",
"Standardized Mortality Ratio"
],
"content": "1. Introduction\n\nDue to the COVID-19 pandemic crisis and the subsequent COVID-19 mass vaccination campaign, the interest has hugely soared in publicly available data on all-cause mortality. For example, data from England and Wales show in 2022, in comparison to the previous average five-year reference period, an excess mortality with a trend driven by more deaths than expected starting in March 2022.1 From April 2021 to the end of May 2023 (the period covered by the ONS dataset) the total excess mortality amounted to 129,801 deaths above the five-year average.2 A similar trend occurs in many other countries in the European Union (EU), as indicated by the graphs and maps provided by the European Mortality Monitoring Project (EuroMoMo), a routine public health mortality monitoring system aimed at detecting and measuring excess deaths related to public health threats across EU countries. According to EuroMoMo, the excess deaths in 2022 were 328,047 in 2022 and 305,301 in 2021 (Graphs and maps — EUROMOMO, accessed May 1, 2024). This is clearly an anomaly, as previous mortality shocks over the past 120 years have almost always been followed by immediate rebounds back, in one to two years,3 with normalization of mortality risk.\n\nEngland and Wales benefit from one of the best public health data collection systems in the world, and are therefore uniquely positioned to monitor and investigate the above-mentioned phenomenon.1 Moreover, the Office for National Statistics (ONS) of the United Kingdom (UK) has published all-cause mortality data in England,4 stratified according to COVID-19 vaccination status, thus overcoming the intrinsic limitation of just identifying deaths due to COVID-19, as for instance happens so far in Italy and in most if not all EU countries, and allowing a direct assessment of the eventual consequences of COVID-19 vaccination for individual as well as public health in terms of change not only of COVID-19 mortality but also of all-cause mortality. In addition, the UK vaccinated more than 50% of its eligible population in the first four months of 2021 and by the end of 2021, 77% received at least one dose,5 thus exceeding the aforementioned threshold earlier than most of the other EU countries. It is therefore possible that the trends observed in England and Wales anticipate what will later occur in EU.\n\nWe decided therefore to analyze the ONS public data on all-cause mortality according to vaccination status, starting from the rates already officially provided by the ONS itself on its website.4 We calculated the rate ratios RR by vaccination status for every age group. Furthermore, due to month-to-month variation in the populations of individual vaccination status, we decided to calculate Standardized Mortality Ratios (SMRs) for those vaccinated with any dose in the different age groups, and to evaluate any potential emerging trends over time. A previous version of this study, dealing with UK ONS data from January to May 2021, is available on Preprints.org.6\n\n\n2. Methods\n\nIn this retrospective study we collected data from the UK ONS web-based platform.4 This platform gathers total mortality data by vaccination status from April, 2021 until May, 2023. Data are publicly available under the Open Government license (https://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/, accessed on 12 February 2024), and can therefore be freely analyzed and published provided that the source is properly acknowledged.\n\nRelying on the excel file provided by this platform, we utilized data from the spreadsheet named “Table 2”(extended data), inasmuch as, differently from other spreadsheets, it provides proper stratification by age and vaccination status to perform an estimate of the Standardization Mortality Rate (SMR) and Relative Risks (RR) for the All-causes death and Non-COVID-19 deaths variable. We could not consider Deaths involving COVID-19 inasmuch from the UK ONS dataset, the absolute frequency of deaths in many vaccination statuses and many age group indicated for this variable was <3 mostly for the younger age groups and for many months of the year 2023. We were therefore unable to reliably calculate the RRs and SMRs. The spreadsheet used for this analysis provides seven age groups (18–39, 40–49, 50–59, 60–69, 70–79, 80–89, 90+ years) and each age group is further subdivided into several classes based on vaccination status:\n\n• Unvaccinated,\n\n• First dose less than 21 days before (1D<21d),\n\n• First dose at least 21 days before (1D≥21d),\n\n• Second dose less than 21 days before (2D<21d),\n\n• Second dose at least 21 days before (2D≥21d),\n\n• Third dose or booster less than 21 days before (3D<21d),\n\n• Third dose or booster at least 21 days before (3D≥21d).\n\nEven if the ONS marks with a “u” (unreliable) any rates arising from a number of death lower than 20, nonetheless we decided to consider groups with a minimum of 10 deaths. Though being aware that the lower the number of deaths, the greater the uncertainty on both the rates and the RRs, this choice allowed us to identify trends of RR over time for each age group. Given the extremely variable nature of the RR trend over time, we decided to understand if this phenomenon was related to the distribution of populations between the various vaccination statuses and for each month of observation. In this regard, we created stacked graphs, in order to analyze the population distributions of the vaccination status for each age group and for each month of the entire observation period, inserting on the y-axis the person-years and on the x-axis the observation months (Supplementary materials, Tables S1-S7(extended data) and Figures S1A/B-S7A/B)((extended data)). From the stacked graphs, a dynamic distribution emerged over the entire observation period for all vaccination statuses. Furthermore, for all age groups was observed an almost constant distribution of the Unvaccinated population over period, unlike the 18-39 and 40-49 age groups where, for the first months of the observation, these groups were more representative compared to other vaccination status. Based on these observations, in order to manage the dynamic distribution of the vaccination statuses month per month, we decided to calculate the SMRs for each observation month. From the calculation of the SMRs boxes indicating <3 deaths were excluded. Finally, for the 18-39, 40-49 age groups we decided do not consider the first six months and the first three months respectively while for the 50-59 we did not consider the first month, in order to compare a roughly constant distribution over time of the Unvaccinated population with the Vaccinated population and obtain a reliable estimate of the SMRs. This decision was made considering a percentage variation of no more than 1% between months in the unvaccinated population. Subsequently, we investigated the relation between SMRs and observation months applying a simple regression model and using SMRs as dependent variable and the observation months as independent variable. Finally, we calculated the intersection of the regression line with the reference line for the unvaccinated (y=1) to identify where possible, or predict where not, the moment in which deaths from all causes in the vaccinated group exceed those of the unvaccinated.\n\nTo calculate the relative risk (RR) between the vaccinated and unvaccinated populations, we used the age-standardized rates indicated in the excel files provided by the UK ONS.4 Their 95% confidence intervals (CI) were calculated according to the following formula7,8:\n\nThe SEln(RR) was calculated for each vaccination status of each of the age groups according to the formula:\n\nWhere, for each year, “V.Pop.” represents the vaccinated population, “Un.Pop.” represents the unvaccinated population, and “Stand.D.Exp.” represents the expected standardized deaths, that is, the deaths that would occur by applying the standardized rates to the real population, calculated according to the formula:\n\nThe choice to use the “Expected Standardized Deaths” is justified by the fact that the calculated RR expresses the ratio between two standardized rates based on the European population. The P value was calculated according to Altman and Bland9:\n\nTo calculate SMR indirect standardization method was applied according to Naing (2000).10 Before to use the simple regression model, all the assumption of the model was verified: scatter plot was created to verify the linear relationship between variables, Shapiro-Wilk normality test was used to verify the residual distributions and Breusch-Pagan test was used to verify homoscedasticity of the variance of errors. To calculate the intersection of the regression line with the reference line of the unvaccinated for each age group we indicated the observation months with a progressive number and solved the equation of the regression line for x and assigning y=1. The x value obtained was compared with the numbers assigned of the observation months so that we could identify a specific moment in the observation period.\n\nData was processed using R studio (version 2023.09.0).\n\n\n3. Results\n\nThe UK ONS dataset we investigated is the latest version available.4 It is based on the population in Census 2021, linking Census deidentified records to National Health Service (NHS) numbers. People with no NHS number or multiple entries are not included.\n\nThe individuals were then linked via NHS number to vaccination data from the National Immunisation Management Service (NIMS) and ONS death registrations. The population was restricted to people in England, alive on 1 April 2021. Overall, ONS dataset population (51,786,812 people) covers 91.6% of the England population on Census Day 2021. The excluded population therefore amount to almost 4,600,000 people. Furthermore, 103,142 were excluded due to erroneous or inconsistent vaccination data, so the overall excluded population amounts to almost 4,700,000 people.\n\nFinally, of the 1,149,784 deaths that occurred in England between 1 April 2021 and 31 May 2023, 90.6% (1,041,524) could be linked to individuals in the 2021 Census.\n\nThe stacked graphs showed a dynamic distribution over all observation period whose percentages and absolute frequencies are reported in Supplementary Material (Tables S1-S7 and Figures S1A/B–S7A/B) (Extended data).38\n\nAll-causes mortality rate ratios RR according to vaccination status are shown in Supplementary, Tables S8-S14(Extended data)38 and Figures S8-S14(Extended data).38 Similarly, RRs for non-COVID19 related deaths are shown in Tables S15-S21(Extended data)38 and Figures S15-S21(Extended data).38 Main results for both mortality causes are summarized below.\n\nDeaths from all causes:\n\nIn all age groups, those vaccinated with the first dose at least 21 days ago have a significantly higher risk of death from all causes than those not vaccinated in almost all months of the entire period, except for the 18-39 age group in which the RRs are significatively higher than 1 in half the months. The average RR values in all age groups are between 1.7 and 2.3, except for the 18-39 years group where the average is 1.5. In the age groups 18-39, 60-69, and older RRs present initial peaks higher than 3, up to a maximum of 5.5 in the 70-79 age group.\n\nAs regards those vaccinated with 2 doses at least 21 days ago, in the age groups starting from 60 years, the risk of death from all causes in the initial months is much lower than the unvaccinated, with a tendency to increase. Since around a third of the entire period (between October and December 2021) RRs significantly exceeds the reference value, remaining higher in almost all the remaining months, although not significatively in the last few months for 60-69 and 90+ years age groups.\n\nThe RRs for those vaccinated with three doses at least 21 days ago, for the age groups 60-69 years and older, present a growth trend which, starting from values much lower than one, reaches and exceeds the reference value:\n\n• for the 60-69 years age group, the risk of death significantly exceeds that of the unvaccinated in the months of November and December 2022 and remains in the following months not significantly different from that of the unvaccinated;\n\n• for the 70-79 years age group the RR exceeds the reference value in June 2022 and always remains significantly higher, apart from the months of September 2022 and May 2023 where the values are not significative;\n\n• for the 80-89 years age group the RR exceeds the reference value in April 2022, reaches the maximum value (RR = 2.29, CI95 = 2.04-2.58) and then stabilizes on values always significantly higher than 1;\n\n• for vaccinated people aged 90 years and over, the reference value is exceeded in April 2022 (RR = 1.13, CI95 = 1.02-1.26), then remaining at values always significantly higher than 1, with a maximum of 1.85 in November 2022.\n\nDeaths non correlated to COVID19\n\nThe rate ratios (RR) from non-Covid causes follow the trends already seen for deaths from all causes, with slightly higher values. Therefore, the above considerations can be repeated.\n\nAge groups\n\nThe results of all regression models performed for the all-causes deaths and non-COVID19 deaths variable and for each age group are summarized in Table 1.\n\nThe regression model for 18-39 age group showed coefficient of determination R2=0.601 and a p-value <0.0001 for the All-causes death variable. For the non-COVID19 deaths regression model showed a R2=0.500 and a p-value=0.0005 (Figure 1). Both variables showed the intersection of the regression line in January 2023.\n\nThe regression model for 40-49 age group showed coefficient of determination R2=0.712 and a p-value <0.0001 for the All-causes death variable. For the non-COVID19 deaths regression model showed a R2=0.463 and a p-value=0.0003 (Figure 2). The All-causes death variables showed the intersection of the regression line in September 2023 while the non-COVID19 deaths showed the intersection of the regression line in April 2023.\n\nThe regression model for 50-59 age group showed coefficient of determination R2=0.734 and a p-value <0.0001 for the All-causes death variable. For the non-COVID19 deaths regression model showed a R2=0.609 and a p-value<0.0001 (Figure 3). The All-causes death variables showed the intersection of the regression line in July 2023 while the non-COVID19 deaths showed the intersection of the regression line in January 2025.\n\nThe regression model for 60-69 age group showed coefficient of determination R2=0.847 and a p-value <0.0001 for the All-causes death variable. For the non-COVID19 deaths regression model showed a R2=0.745 and a p-value<0.0001 (Figure 4). The All-causes death variables showed the intersection of the regression line in February 2024 while the non-COVID19 deaths showed the intersection of the regression line in May 2024.\n\nThe regression model for 70-79 age group showed coefficient of determination R2=0.860 and a p-value <0.0001 for the All-causes death variable. For the non-COVID19 deaths regression model showed a R2=0.764 and a p-value<0.0001 (Figure 5). The All-causes death variables showed the intersection of the regression line in January 2024 while the non-COVID19 deaths showed the intersection of the regression line in May 2024.\n\nThe regression model for 80-89 age group showed coefficient of determination R2=0.784 and a p-value <0.0001 for the All-causes death variable. For the non-COVID19 deaths regression model showed a R2=0.706 and a p-value<0.0001 (Figure 6). The All-causes death variables showed the intersection of the regression line in April 2023 while the non-COVID19 deaths showed the intersection of the regression line in January 2023.\n\nThe regression model for 90+ age group showed coefficient of determination R2=0.695 and a p-value <0.0001 for the All-causes death variable. For the non-COVID19 deaths regression model showed a R2=0.705 and a p-value<0.0001 (Figure 7). The All-causes death variables showed the intersection of the regression line in September 2022 while the non-COVID19 deaths showed the intersection of the regression line in May 2022.\n\n\n4. Discussion\n\nIn the present study, we analyzed the UK ONS data on all-cause mortality according to vaccination status, which are publicly available on the ONS institutional website.4 The main findings of our analysis are:\n\n(a) compared with unvaccinated, vaccinated with one or two doses show, in the period April 2021-May 2023, a substantially higher risk of all-causes and non-COVID-19 deaths. Indeed, for both causes people vaccinated with one dose show a RR significatively higher than 1 through almost the whole period and in any of the age groups, except the 18-39 years, in which it is significatively higher in half the period. In people who received the second dose, from 60 to 90+ years of age the risk of all-causes and non-COVID-19 death is significatively higher than in unvaccinated people through about the final two thirds of the period. It should be noted that from 50 to 90+ years of age the RRs of all-causes and non-COVID-19 death have implausibly low initial values.\n\n(b) Also vaccinated with three doses have incredibly low initial values of RR both for all-causes and for non-COVID-19 deaths. Their RRs, for people aged 60-69 and older progressively grow up to reach and exceed the reference value from 60 years of age, and from 70 years and over the RRs remain significantly greater than 1.\n\n(c) A linear growth trend is revealed by regression analysis of Standardized Mortality Ratios of people vaccinated with any dose compared to the unvaccinated across all age groups, for both all-cause and non-COVID-19 deaths. The regression lines, both for all-cause deaths and for non-COVID-19 ones, start from very low values for all the age groups. For the age groups 18-39, 80-89 and 90+ years both regression lines intersect the reference line of unvaccinated during the study period. The same occurs for the age 50-59, limited to non-COVID-19 deaths, For the other age groups, we have predicted the month of the intersection (see Table 1).\n\nThe results found for the RRs of the first and second doses are confirmed in other studies, e.g. in two studies carried out in an Italian province.11,12 Both studies show a significantly higher risk of death from all causes for those vaccinated with one and two doses compared to the unvaccinated. Furthermore, they show an implausible high protection of the vaccine against deaths from all causes, too high to be attributed to protection from deaths from COVID-19, which are a minority percentage of total deaths. Both studies, however, are affected by important biases. The main one is the so-called Immortal Time Bias (ITB), as highlighted in an intervention published in an Italian epidemiology journal.13 After correction of ITB, the unlikely protection provided by the third dose against death from all causes disappears entirely. Another recent study,14 was based on the same dataset kindly provided by the authors of the article,12 but corrected for the ITB. In its multivariable analysis, this study shows higher all-cause death hazard ratios (HRs) for individuals vaccinated with one and two doses compared to unvaccinated, and no protection against all-cause deaths for population vaccinated with 3 or more doses. Furthermore, the study14 found a small but statistically significant reduction in life expectancy for vaccinated people with two and three or more doses\n\nThe present study also shows extremely low initial risks of all-causes and nonCOVID-19 death, as well in the analysis of the RRs for those vaccinated with two and three doses, as in that of the SMRs for those vaccinated with any dose compared to the unvaccinated. These results appear difficult to justify, especially when referring to non-COVID-19 deaths, unless admitting the presence of some important selection bias. In fact, if the populations being compared were homogeneous, the risk of death from causes other than COVID-19 should be about zero, and both the RRs and SMRs for non-COVID deaths should not differ significantly from 1.\n\nUnfortunately, there is a lack of information on the health status of populations or about other factors that influence the risk of death, so we can only formulate some hypotheses, that are not necessarily alternative.\n\nOne hypothesis might be an underestimation of the unvaccinated population in the ONS dataset. We have seen that the population included in this dataset does not cover the entire population of England recorded in the 2021 census. The population left out of the dataset is around 4,700,000 people. There would be a selection bias with systematic effects throughout the period if this proportion of the total population were not equally distributed between vaccinated and unvaccinated, and if it included a greater proportion of unvaccinated. We can see from the last two ONS reports that, although they cover a larger population than previous reports, the criteria for inclusion (and therefore exclusion) are the same as those based on the previous census. They are therefore subject to the same limitations. The main one is that the excluded population is not randomly selected, and therefore the population covered by the dataset is not representative of the general population. The key to inclusion is having a National Health Service (NHS) number. The probability of a vaccinated person not having an NHS number is virtually zero, because without a number you cannot be vaccinated. However, this is not the case for the unvaccinated, some of whom may not have been registered with a General Practitioner (GP) and therefore do not have an NHS number. As deaths among the unvaccinated are certified in the same way as those among the vaccinated, they cannot escape ONS registration. This would result in a relative overestimation of mortality rates for the unvaccinated and consequently an underestimation of RRs and SMRs for the vaccinated.\n\nAnother possible contributory hypotheses is the so called healthy-vaccinee bias.15–18 In 2021 a lower mortality among the vaccinated can also be explained partly by the healthy-adherer effect, or the healthy-vaccinee bias in the vaccination field. This effect is much more powerful than commonly thought: in fact, voluntary adherence to a treatment can be associated with a nearly halved mortality,19–21 and even with a mortality reduction of 2.5 to 3 or more times15,17,22–24 compared to the mortality of those who do not adhere. This effect is independent of the type of treatment to which one adheres voluntarily, being also found in randomized controlled trials in the placebo adherers (compared with placebo non-adherers). This effect may have several explanations. In the short time, individuals contingently ill tend to postpone vaccination.24,25 In addition, doctors can renounce to vaccinate people considered close to death, whose subsequent death burdens the unvaccinated cohort disproportionately.\n\nHowever, the healthy-adherer effect can be detected over many years,15,17,19,22 because subjects adhering to preventive treatments are usually at the same time more likely to engage in healthy lifestyles than patients not adhering.16,20 A healthy lifestyle includes diet, exercise, lower tobacco and alcohol consumption, less risky behaviors,26 and the search for better health care. These features—difficult to capture in administrative databases—are associated with morbidity and mortality outcomes in observational studies. Moreover, the trust in the intervention to which one adheres can exert a beneficial placebo effect. The healthy-adherer bias is more difficult to correct than the opposite effect of confounding by indication (subjects in worse health conditions are vaccinated first), which is relatively easier to correct, provided it is known e.g. the number of comorbidities, or the Charlson comorbidity index of the groups to be compared.27 Unfortunately, the UK ONS public data do not include any information about comorbidities. It is likely that the healthy-vaccinee bias effect will continue to operate to varying degrees in 2022 and 2023, albeit to a diminishing extent during periods in which vaccination mandates have been in force.\n\nMoreover, it is plausible that the increase in the number of the vaccinated has diluted the opposite effect of confounding by indication.27\n\nA commonly used argument is the better known confounding by indication effect27: it is likely that fragile subjects with multiple diseases have been vaccinated as a priority, followed by the others. However, as the vaccination campaigns proceed, the composition of the vaccinated and unvaccinated populations should result less unbalanced with respect to the pre-existing state of health. The ONS declare that “Changes in non-COVID-19 mortality by vaccination status are largely driven by the changing composition of the vaccination status groups. This is because of the priority given to clinically extremely vulnerable people or with underlying health conditions, and differences in timing of vaccination among eligible people\".3 However, a priority was also given to the healthier population of health workers. Moreover, the most fragile part of the population prioritized for the vaccination is a smaller portion (especially in the younger ages), and the composition of each age group progressively tends to be similar to that of the unvaccinated, in terms of general health conditions. Therefore, a decreasing trend would be expected, both because of the decreasing weight of the fragile fraction compared to the overall group and because of the harvesting effect, described below.\n\nThe RRs of the first doses generally show high initial mortality peaks, possibly linked to the priority given to the fragile subjects. The early death of the most fragile causes that those who move on to the second dose are healthier overall. It is unfortunate that the last two ONS datasets do not provide data for the first three months of 2021, corresponding to the start of the vaccination programme. In fact, since vaccinations began with the older classes, in April 2021 the latter had not only completed the vaccination with the first dose, but had already started the second. Therefore our hypothesis can be confirmed only in the age groups 18-39 and 40-49, where one can clearly perceive the initial mortality peak of the first doses, probably already decreasing, followed by the initial mortality peak of the second doses, starting from lower values and with a lower maximum compared to that of the first doses.\n\nAs regards the third doses, the initial mortality peak disappears in all age groups, suggesting that many of the most “fragile” people have already died, and that a ‘healthy-vaccinee effect’ might partly explain the initial very low RR values.\n\nExamining the SMR graphs, we note that, apart from the elderly, the points relating to all-cause deaths and non-COVID-19 deaths tend to overlap over time. This may indicate that the impact of COVID-19-related deaths vanishes, and that the risk of all-cause death and of deaths not related to COVID-19 is nearly the same. In fact, in the ONS dataset, approaching the end of the observation period, the COVID-19-deaths for the different vaccination statuses show an ever-increasing number of values indicated with <3, what prevents one from calculating both the RRs and the SMRs. This justifies the choice not to take into consideration COVID-19 deaths, but only all-cause and non-COVID-19 deaths.\n\nHence, the insistent push towards further vaccinations seems hardly motivated.\n\nAgain, examining the SMRs, the fact that initially the regression line of non-COVID-19 deaths is above that of all-cause deaths might indicate that the vaccine initially has a protective effect on COVID-19 deaths, thus lowering the risk of all-cause deaths, that include those COVID-19 related, among vaccinated people. The fact that they subsequently converge may indicate either that the vaccine gradually loses its protective effectiveness, or that the risk of COVID-19 deaths decreases due to the increasingly lower lethality of the new variants, or that the two causes act together.\n\nThe SMR graphs allow one to make a further consideration: in the 80-89 age group the convergence of the lines of all-cause deaths is much attenuated, and in the 90+ age group the lines are almost parallel, as one can see from the regression coefficients that differ less and less. This might indicate that COVID-19 still represents a risk for the elderly and that the vaccine therefore protects them by reducing the risk of all-cause deaths. Yet, it might also be due to the fact that the lower lethality of the new variants is offset by the fact that the vaccinated people get infected more than unvaccinated28–35 and that by taking additional doses they are temporarily protected from the risk of dying from COVID-19.\n\nLast but not least: why are the SMRs of non-COVID-19 related deaths increasing? Why should the risk of those vaccinated with any dose increase compared to that of the unvaccinated? Apart from the risk of immediate adverse reactions/events, the doubt naturally arises that the vaccine, might cause damage to the immune system, exposing the vaccinated to a greater risk of death from pathologies non-COVID-19 related36,37\n\n\n5. Conclusions\n\nThe English all-cause and non-COVID-19 mortality data by vaccination status, released by the UK ONS for the 26 months from April 2021 to May 2023, were analyzed by age group and vaccination status. Our findings show that all-cause deaths SMRs were increasing in any of the age groups considered. All-cause death SMRs, initially well below 1 for every age group, due to their increase, since a certain date exceeded the reference value of the unvaccinated people for the age groups 18-39, 80-89 and 90+. For the other age groups, it is possible to predict the date in which the SMR would reach the value 1, intersecting the unvaccinated level, provided that this trend is consistently maintained.\n\nNon-COVID-19 SMR values show a very similar trend: initially they are much lower than 1, but it is not plausible such a vaccine protection from non-COVID-19 deaths. Therefore, this suggests significant biases in the ONS dataset, leading to an underestimation of the risks for the vaccinated. Regardless of the interpretative hypotheses, the fact that all-cause mortality SMRs in vaccinated increase over time compared to those of unvaccinated requires further, urgent investigation.\n\nIn any case, we hope that the ONS will resume the publication of the mortality data series by vaccination status, interrupted in May 2023, and that its example will be followed by other countries.\n\nMoreover, the precautionary principle should suggest a moratorium on extensive vaccination campaigns, pending the acquisition of valid explanations of the alarming phenomenon observed.\n\n\nInstitutional review board statement\n\nNot applicable.\n\n\nInformed consent statement\n\nNot applicable.\n\n\nAuthor contributions\n\nConceptualization, M.A., G.M., G.D.P., M.C. and A.D.; methodology, formal analysis and writing—original draft preparation, M.A., G.M., G.D.P., M.C. and A.D.; writing—review and editing, M.A., G.M., G.D.P., M.C. and A.D. All authors have read and agreed to the published version of the manuscript.\n\n\nDisclaimer/publisher’s note\n\nThe statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.",
"appendix": "Data availability statement\n\nThe data presented in this study are openly available on the UK ONS web page entitled “Deaths by vaccination status, England”, available online: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/datasets/deathsbyvaccinationstatusengland (accessed on 1 May 2024).\n\nZenodo: Supplementary Materials, https://doi.org/10.5281/zenodo.13080361 38\n\nThis project contains the following extended data:\n\n• Supplementary Tables 1-7 (population).xlsx\n\n• Supplementary Tables 15-21 (mortality non-Covid deaths).xlsx\n\n• Supplementary Tables 8-14 (mortality all causes).xlsx\n\n• Supplemetary figure.pptx\n\n• Table 2\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgement\n\nDr. Chiara Giove, for administrative support\n\n\nReferences\n\nHussain Z: England and Wales have seen rise in excess deaths in 2022. BMJ. 2022; 378: o2283. Publisher Full Text\n\nDeaths registered weekly in England and Wales, provisional: week ending 26 May 2023. (accessed on May 1, 2024). Reference Source\n\nSchöley J, Aburto JM, Kashnitsky I, et al.: Life expectancy changes since COVID-19. Nat. Hum. Behav. 2022; 6: 1649–1659. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDeaths by vaccination status, England. (accessed on May 1, 2024). Reference Source\n\nOur world in data - Share of people vaccinated against COVID-19, Apr 25, 2021. (accessed on May 1, 2024). Reference Source\n\nDonzelli A, Malatesta G, Di Palmo G, et al.: All-Cause Mortality According to COVID-19 Vaccination Status: an analysis of the UK Office for National Statistics Public Data. Preprints. 2023; 2023020414. Publisher Full Text\n\nSoliani L: Statistica Applicata. Parma (PR), Italy: Uni. Nova; 2008.\n\nNorman G, Streiner D: Biostatistica. 2nd ed.Rozzano (MI): Casa Editrice Ambrosiana; 2015.\n\nAltman DG, Bland JM: How to obtain the P value from confidence interval from a. BMJ. 2011; 343: d2304. Publisher Full Text\n\nNaing NN: Easy way to learn standardization: direct and indirect methods. Malays. J. Med. Sci. 2000 Jan; 7(1): 10–15. PubMed Abstract | Free Full Text\n\nAcuti Martellucci C, Flacco ME, Soldato G, et al.: Effectiveness of COVID-19 Vaccines in the General Population of an Italian Region before and during the Omicron Wave. Vaccines. 2022; 10: 662. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRosso A, Flacco ME, Soldato G, et al.: COVID-19 Vaccination Effectiveness in the General Population of an Italian Province: Two Years of Follo Up. Vaccines. 2023; 11: 1325. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBerrino F, Donzelli A, Bellavite P, et al.: COVID-19 vaccination and all-cause and non-COVID-19 mortality. A revaluation of a study carried out in an Italian Province. Epidemiol. Prev. 2023 Nov-Dec; 47(6): 374–378. English. PubMed Abstract | Publisher Full Text\n\nAlessandria M, Malatesta GM, Berrino F, et al.: A Critical Analysis of All-Cause Deaths during COVID-19 Vaccination in an Italian Province. Microorganisms. 2024; 12: 1343. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPinsky PF, Miller A, Kramer BS, et al.: Evidence of a healthy volunteer effect in the prostate, lung, colorectal, and ovarian cancer screening trial. Am. J. Epidemiol. 2007; 165: 874–881. PubMed Abstract | Publisher Full Text\n\nDormuth CR, Patrick AR, Shrank WH: Statin adherence and risk of accidents: a cautionary tale. Circulation. 2009; 119: 2051–2057. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVestbo J, Anderson JA, Calverley PM, et al.: Adherence to inhaled therapy, mortality and hospital admission in COPD. Thorax. 2009; 64: 939–943. Publisher Full Text\n\nLadova K, Vlcek J, Vytrisalova M, et al.: Healthy adherer effect - the pitfall in the interpretation of the effect of medication adherence on health outcomes. J. Eval. Clin. Pract. 2014; 20: 111–116. PubMed Abstract | Publisher Full Text\n\nCoronary Drug Project Research Group: Influence of adherence to treatment and response of cholesterol on mortality in the Coronary Drug Project. N. Engl. J. Med. 1980; 303: 1038–1041. PubMed Abstract | Publisher Full Text\n\nSimpson SH, Eurich DT, Majumdar SR, et al.: A meta-analysis of the association between adherence to drug therapy and mortality. BMJ. 2006; 333: 15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJackson LA, Jackson ML, Nelson JC, et al.: Evidence of bias in estimates of influenza vaccine effectiveness in seniors. Int. J. Epidemiol. 2006; 35: 337–344. PubMed Abstract | Publisher Full Text\n\nHorwitz RI, Viscoli CM, Berkman L, et al.: Treatment adherence and risk of death after a myocardial infarction. Lancet. 1990; 336: 542–545. Publisher Full Text\n\nFurst T, Straka R, Janosek J: Healthy vaccinee effect: a bias not to be forgotten in observational studies on COVID-19 vaccine effectiveness. Pol. Arch. Intern. Med. 2024 Feb 28; 134(2): 16634. Publisher Full Text\n\nFürst T, Bazalová A, Fryčák T, et al.: Does the healthy vaccinee bias rule them all? Association of COVID-19 vaccination status and all-cause mortality from an analysis of data from 2.2 million individual health records. Int. J. Infect. Dis. 2024 May; 142: 106976. PubMed Abstract | Publisher Full Text\n\nMcCarthy NL, Weintraub E, Vellozzi C, et al.: Mortality rates and cause-of-death patterns in a vaccinated population. Am. J. Prev. Med. 2013 Jul; 45(1): 91–97. PubMed Abstract | Publisher Full Text\n\nRedelmeier DA, Wang J, Thiruchelvam D: COVID Vaccine Hesitancy and Risk of a Traffic Crash. Am. J. Med. 2023; 136: 153–162.e5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRemschmidt C, Wichmann O, Harder T: Frequency and impact of confounding by indication and healthy vaccinee bias in observational studies assessing influenza vaccine effectiveness: A systematic review. BMC Infect. Dis. 2015; 15: 429. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEythorsson E, Runolfsdottir HL, Ingvarsson RF, et al.: Rate of SARS-CoV-2 Reinfection During an Omicron Wave in Iceland. JAMA Netw. Open. 2022; 5(8): e2225320. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTseng HF, Ackerson BK, Bruxvoort KJ, et al.: Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. Nat. Commun. 2023; 14: 189. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChemaitelly H, Ayoub HH, Tang P, et al.: Long-term COVID-19 booster effectiveness by infection history and clinical vulnerability and immune imprinting: a retrospective population-based cohort study. Lancet Infect. Dis. 2023 Jul; 23(7): 816–827. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTamandjou C, Auvigne V, Schaeffer J, et al.: Effectiveness of second booster compared to first booster and protection conferred by previous SARS-CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France. Vaccine. 2023 Apr 24; 41(17): 2754–2760. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShrestha NK, Burke PC, Nowacki AS, et al.: Effectiveness of the Coronavirus Disease 2019 Bivalent Vaccine. Open Forum Infect. Dis. 2023 Apr 19; 10(6): ofad209. PubMed Abstract | Publisher Full Text | Free Full Text\n\nQassim SH, Chemaitelly H, Ayoub HH, et al.: Population immunity of natural infection, primary-series vaccination, and booster vaccination in Qatar during the COVID-19 pandemic: an observational study. EClinicalMedicine. 2023 Jul 20; 62: 102102. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChalupka A, Richter L, Chakeri A, et al.: Effectiveness of a fourth SARS-CoV-2 vaccine dose in previously infected individuals from Austria. Eur. J. Clin. Investig. 2024 Mar; 54(3): e14136. PubMed Abstract | Publisher Full Text\n\nShrestha NK, Burke PC, Nowacki AS, et al.: Risk of Coronavirus Disease 2019 (COVID-19) among those up-to-date and not up-to-date on COVID-19 vaccination by US CDC criteria. PLoS One. 2023 Nov 8; 18(11): e0293449. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang H, Xu Q, Zhao C, et al.: An immune evasion mechanism with IgG4 playing an essential role in cancer and implication for immunotherapy. J. Immunother. Cancer. 2020 Aug; 8(2): e000661. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUversky VN, Redwan EM, Makis W, et al.: IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein. Vaccines (Basel). 2023 May 17; 11(5): 991. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlessandria M: Supplementary material. Zenodo. 2024. Publisher Full Text"
}
|
[
{
"id": "311454",
"date": "19 Aug 2024",
"name": "Jarle Aarstad",
"expertise": [
"Reviewer Expertise Applied statistical 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\nDear Editor and authors,\nThank you for giving me the opportunity to referee the manuscript entitled “All-cause mortality according to COVID-19 vaccination status: An analysis of the UK office for National statistics public data”. I find the article very interesting and illuminating, particularly comparing all-cause mortality with non-covid mortality, and along with a very good discussion, it increases the study’s validity and adds value to the study of covid-vaccines’ potential mortality effect. Concerning the Introduction, the authors relevantly address the research question and study objective. I believe, however, that the study by Mostert et al. (2024)(Ref-1) merits attention concerning excess mortality in Western countries. I assume the calculations are correct regarding the statistical analyses of the RRs CIs, but I recommend one or two references on which you base the calculations. Also, I did not understand what you mean by “standardized rate”. Altogether, I would like you to explain that part better, particularly for an audience unfamiliar with the approach, eventually in an appendix. I follow the logic in section 3.4, but I suspect you compare never vaccinated with ever vaccinated. Is that correct? I assume yes, but it was a bit unclear for me. In the Figures, you include the number of months, but would it be better to include their names? E.g., Apr. 2021, etc. In Figures 2, 3, 4, 5, and partly 6, the intersections are out of the sample, which you should state in the text. Very good and illuminating discussion. As you apply English/Welsh data, you may refer to the following web page by the Office for National Statistics, showing that unvaccinated tended to live in more deprived areas, urban areas, or social rented housing, were not born in the UK or did not have English as a main language, have never worked or are long-term unemployed, limited a lot by a disability, and are male (among you more men die than women). https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/articles/coronaviruscovid19latestinsights/vaccines Addressing the above mentioned issues adequately, I argue the study will meet the indexing standards. I wish you all the best when reviewing the manuscript.\nSincerely, Referee 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? 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? Yes",
"responses": [
{
"c_id": "13143",
"date": "16 Jan 2025",
"name": "Alberto Donzelli",
"role": "Author Response",
"response": "Dear Dr. Jarle Aarstad, We want to thank you for your advice which contribute to improve our paper. Below are the answers to your questions. Dear Editor and authors, Thank you for giving me the opportunity to referee the manuscript entitled “All-cause mortality according to COVID-19 vaccination status: An analysis of the UK office for National statistics public data”. I find the article very interesting and illuminating, particularly comparing all-cause mortality with non-covid mortality, and along with a very good discussion, it increases the study’s validity and adds value to the study of covid-vaccines’ potential mortality effect. Q. Concerning the Introduction, the authors relevantly address the research question and study objective. I believe, however, that the study by Mostert et al. (2024)(Ref-1) merits attention concerning excess mortality in Western countries. Author’s response: Thank you for your valuable feedback. We have added the reference in the \"Introduction\" section. Q. I assume the calculations are correct regarding the statistical analyses of the RRs CIs, but I recommend one or two references on which you base the calculations. Author’s response: sorry, but we think do not understand, the reference regarding the statistical analyses of the RRs CIs are indicated just before the colons in the sentence above the formula and they are mentioned as 8 and 9 references. Q. Also, I did not understand what you mean by “standardized rate”. Author’s response: sorry, you are right. For “standardized rate” we mean the Age-standardised mortality rates per 100,000 person-years, standardised to the 2013 European Standard Population using five-year age groups from those aged 10 years and over as defined in \"Note 1\" of the spreadsheet called \"Notes\" of the ONS dataset. We changed the sentence. Q. Altogether, I would like you to explain that part better, particularly for an audience unfamiliar with the approach, eventually in an appendix. Author’s response: sorry but we think do not understand, could you be more specific? We inserted all the steps of the calculations performed by us and we would not know which other steps we could describe in a further appendix. Q. I follow the logic in section 3.4, but I suspect you compare never vaccinated with ever vaccinated. Is that correct? I assume yes, but it was a bit unclear for me. Author’s response: exactly, you are correct, we used the same terminology used in the Table 2 of the ONS dataset. Q.In the Figures, you include the number of months, but would it be better to include their names? E.g., Apr. 2021, etc. Author’s response: thank you, we replaced the numbers with the names. Q. In Figures 2, 3, 4, 5, and partly 6, the intersections are out of the sample, which you should state in the text. Author’s response: sorry, you are right. We added a sentence that specifics this aspect. Q. Very good and illuminating discussion. As you apply English/Welsh data, you may refer to the following web page by the Office for National Statistics, showing that unvaccinated tended to live in more deprived areas, urban areas, or social rented housing, were not born in the UK or did not have English as a main language, have never worked or are long-term unemployed, limited a lot by a disability, and are male (among you more men die than women). https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/articles/coronaviruscovid19latestinsights/vaccines Addressing the above mentioned issues adequately, I argue the study will meet the indexing standards. Author’s response: thank you for this advice. We have added a reflection on this aspect in the “Discussion” section. I wish you all the best when reviewing the manuscript."
}
]
},
{
"id": "342218",
"date": "07 Jan 2025",
"name": "Stefan Pilz",
"expertise": [
"Reviewer Expertise Epidemiology and clinical research in endocrinology"
],
"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 retrospective study on the mortality rate according to vaccination status against SARS-CoV-2 in the UK. Based on publicly available national health data the authors show that mortality risk is, in general (for most time periods and age groups analyzed), higher in vaccinated versus unvaccinated individuals. SMRs in vaccinated individuals are lower than one in early periods of their observation period, but progressively increase over time and exceed one in several age groups suggesting that relative mortality risk progressively increases over time after vaccination. The discussion of these findings is well-written and includes several interesting views on potential biases in their findings. Overall, this is an interesting and important paper. I have only minor comments. The authors should aim to carefully explain very clearly the underlying analyses of their Tables and Figures so that they can also stand alone: e.g. in Table 1 it may not be clear for the reader that this is a regression analysis of SMRs and observation months (this has only been described in the text). The discussion is great, but a brief overall limitations section may improve the quality of the paper (e.g., retrospective study design, only age group data but no individual participant data, etc.). Several limitations have been nicely discussed but I would nevertheless suggest such a brief limitations section. The authors may check whether this article meets all the requirements of the STROBE guidelines. I do not request a STROBE guideline Table as a Supplement although this may be considered. The authors should carefully re-check the spelling and grammar of this article as there are some slight improvements required. E.g., Page 10, second paragraph, second line from the bottom “the risk of death” should be corrected to “the risk difference of death…”. In addition, some parts of the article may be difficult to read and understand for the reader. Consider improving this. In the Abstract the authors write that “the best way can be the analysis of all-cause mortality by vaccination”. I would rather be cautious to state “the best way” and re-phrase this to something like” Assessment of its real-world effect can be performed by analysis of all-cause mortality by vaccination status”. In the results section of the Abstract the last sentence is rather a discussion of the data than a results presentation. Consider revising and/or removing some parts to the discussion of the Abstract. Regarding data analyses and discussion it would be great (if possible depending on statistical power) to focus also on groups with vaccinations less than 21 days before, as for these groups hardly any (or only minimal) vaccine effectiveness on COVID-19 mortality can be assumed so that any mortality difference may well reflect some sort of bias. No problem if the authors are not willing to address this. Regarding the overall conclusions I would suggest being more cautious regarding strong statements (such as a moratorium on promoting mass vaccination campaigns should be implemented) as the findings are only observational and require further confirmation and more in-depth investigations at best with inclusion of more potential confounders and IPD.\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/13-886
|
https://f1000research.com/articles/11-46/v1
|
14 Jan 22
|
{
"type": "Method Article",
"title": "Using Gagne’s instructional design to teach communication skills in phlebotomy education through role-play",
"authors": [
"Amani Y. Owaidah"
],
"abstract": "Background: Phlebotomy is a medical procedure that is performed frequently in the blood collection activities of medical institutions. The procedure involves close interaction with different types of patients—some of whom are cooperative and others, who, for many reasons, are not (for example, patients who have a fear of needles). Blood extraction is an essential skill in several medical specialties, such as in laboratory sciences. Lesson planning in phlebotomy education is mainly focused on procedural skills, and very little attention is given towards teaching communication skills despite the close patient interaction in phlebotomy. In this paper, I propose a lesson plan for teaching communication skills to medical laboratory sciences and nursing students based on Gagne’s instructional design. Methods: The training session included two main parts: training session using Gange’s instructional design and at the end of the session, the participants were surveyed for the effectiveness of the training session. Results: 17 participants were included in the study. Overall, the majority of the participants were highly satisfied with the effectiveness of the training session in teaching communication skills with all seven survey questions receiving a mean score of 4.58 on a Likert scale of 1-5. Conclusion: We demonstrated the effectiveness of Gange’s instructional beyond theoretical lesson planning to teach communication skills through role-play in phlebotomy education.",
"keywords": [
"communication skills",
"phlebotomy",
"medical education",
"trypanophobia"
],
"content": "Introduction\n\nPhlebotomy, also known as venipuncture, denotes the process of drawing blood, and it is considered one of the most common medical procedures in healthcare.1 Often performed by doctors, nurses, laboratory staff, or specialized phlebotomists, it plays a pivotal role in all laboratory analyses, patient diagnoses, treatments, research, and transfusions. As many countries do not have specialized phlebotomy programs, the procedure is often embedded in the curriculum of most medical specialties.2\n\nIn the field of medical education, phlebotomy has always been taught according to the apprenticeship model, which typically uses the “see one, do one, teach one” approach.3 In particular, simulators such as mannequins, which offer a physical model of a patient’s arm, have been used to provide students the opportunity to practice a procedure before performing it on a real patient.4 By using simulations the potential patient risk is reduced in clinical training, which ultimately improves the quality of patient care. Role-play is another teaching strategy that has been used. Students are generally divided into small groups and take turns practicing the steps related to the phlebotomy procedure.4 These main teaching methods focus on the technical and procedural skills of phlebotomy, and neglect the vital skills of communication.\n\nTo perform the procedure in real-life (working) situations, healthcare professionals must interact with patients, some of whom may present anxiety or a fear of needles.5–7 Other patients may be difficult to communicate with, especially when the first attempt to draw blood was unsuccessful. This may cause delays in extracting the sample or distress in the phlebotomy process. Therefore, teaching communication skills in phlebotomy is as vital as teaching technical skills.\n\nComprising nine steps, Gagne’s instructional design has been widely used in medical education as a framework for achieving five main learning outcomes (see Table 1), including intellectual skills, verbal information, cognitive strategies, attitudes, and motor skills.8 In this study, the researcher applied Gagne’s steps to phlebotomy education and outlined a detailed lesson plan that incorporates the teaching of communication skills for the process of phlebotomy.\n\n\nMethods\n\nIn October 2021, a two-hour training session on communication skills based on Gange’s instructional design using role-play was conducted for the fourth year Clinical Laboratory Sciences (CLS) students and interns of CLS and Nursing programs in Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. An email invitation was sent to the students and interns via email. 17 volunteer participants responded to the invitation. The training session was directed by the author, who acted as the trainer for the entire session. A teaching assistant participated to play the role of the patient in the session.\n\nThe program and the study were approved by the ethics committee of Imam Abdulrahman bin Faisal University. All participants provided a signed written informed consent to participate in the training session and study, and the study protocol was approved by the institutional review board of Imam Abdulrahman Bin Faisal University (IRB-2021-03-359). The study was conducted in compliance with the Declaration of Helsinki.\n\nStudents who had essential prior knowledge of the pre-analytical variables that are associated with blood collection. These variables include patient variables (fasting), technique variables (patient identification), and specimen variables (anticoagulant specimen processing).\n\nGaining attention\n\nTo engage students at the start of the session, the presenter (also called trainer) played a video demonstrating how a phlebotomist interacts with a child who comes for blood extraction but is afraid of needles. This video will not only capture the attention of visual and auditory learners, but also triggers the learners’ personal experiences with blood collection. Audio-visual presentation also stimulates auditory learners through audio narration while, the visual learners found themselves engaged by the interactions in the video. Meanwhile, the kinesthetic learners were drawn towards the activities in the video. Meanwhile, through watching the video and based on the situated learning theory, the interaction between the child and the phlebotomist stimulates past memories and facilitates the students to reflect on their past experience and promotes professional growth.9 In addition, the video potentially helped keeping the students focused on the objectives throughout the session through reducing the cognitive load.\n\nInforming the learner of the objectives\n\nTo keep students engaged, the presenter asked the students what they thought about the video before stating the session’s objectives. This was intended to help students appreciate the learning objectives in real work situations. The objective of the session was for students to successfully acquire certain capabilities and skills, including how to approach and greet patients in a positive and friendly manner; communicate effectively with patients who exhibit fear and anxiety; and communicate effectively with cooperative patients.\n\nRecall of prior learning\n\nFor students to benefit from the session, the trainer used the constructivism learning theory approach. It is based on allowing students to rely on their previous knowledge and personal experiences, which is then aligned with new information so that the students can construct their own visual interpretations of real work situations.10 To achieve this purpose, the students were asked about their recent visits to an outpatient clinic or laboratory to perform blood collection. In particular, they will be presented with questions such as a) “Have you experienced fear from a blood collection procedure”?; “Do you know someone, such as a family member or friend, with trypanophobia (phobia of medical procedures)?; and “If yes, how do phlebotomists deal with such a situation?”; “What would you do differently if you were a phlebotomist?” This way, the students were prompted to recall their previous learning experiences and were given approximately five minutes to reflect. This exercise engaged the students’ interpersonal intelligence.\n\nPresenting stimulus\n\nIn this segment of the session, the trainer used role-play to deliver the intended content. Role-play is one of the most widely used teaching methods for the acquisition of communication skills in medical education.11 Tables 2 and 3 outline the role-play scenarios that were presented in the session. The first scenario demonstrates how students should communicate with a cooperative patient, while the second scenario demonstrates how they should communicate with a patient displaying trypanophobia (fear of needles). To ensure that the students remain engaged in the session, the facilitator encouraged them again to recall their personal experiences of visiting a clinic for a blood test.\n\n\n\n1. Phlebotomist.\n\n2. Adult patient.\n\n\n\n• Two chairs.\n\n• Phlebotomy table holding syringes, vacutainers, unlabeled blood collection tubes, and blood test request forms.\n\n\n\n• To demonstrate positive behavior.\n\n• To identify the patient correctly.\n\n\n\n• Greet the patient with a smile and friendly attitude.\n\n• Maintain eye contact.\n\n• Identify the patient correctly.\n\n• Explain the procedure to the patient.\n\n• Maintain a positive attitude throughout the procedure.\n\n\n\n1. Phlebotomist.\n\n2. Adult patient.\n\n\n\n• Two chairs.\n\n• Phlebotomy table holding syringes, vacutainers, unlabeled blood collection tubes, and blood test request forms.\n\n\n\n• To demonstrate positive behavior.\n\n• To demonstrate compassion and reassurance.\n\n• To identify the patient correctly.\n\n\n\n• Greet the patient with smile and friendly attitude.\n\n• Identify the patient correctly.\n\n• Maintain comfortable eye contact.\n\n• Notice the patient’s fear.\n\n• Attempt to comfort the patient before explaining the procedure.\n\n• Be attentive to the patient’s needs.\n\n• Do not undermine the patient’s fear.\n\n• Explain the procedure to the patient.\n\n• Maintain a positive attitude throughout the procedure.\n\nProviding learning guidance\n\nFor each role-play scenario, the trainer used Peyton’s approach to teaching, which comprises four steps: demonstration, deconstruction, comprehension, and performance.12 For the first scenario (a normal, cooperative patient), the trainer began the instruction by demonstrating how students should approach the patient friendly and politely; identify the patient correctly; clearly explain the procedure; label the tubes accurately; and approach the patient for the phlebotomy procedure. Thereafter, the trainer deconstructed each step by explaining the rationale behind it. During deconstruction, students were encouraged to ask questions and comment on the process. By encouraging them to ask questions, the trainer facilitated their understanding, further stimulating them to reflect on previous experiences.\n\nThe second scenario (a trypanophobia patient) required a more explicit demonstration and deconstruction process. The same approach as in the first scenario was used, but the trainer demonstrated more compassion and persuasive skills when the patient (played by a teaching assistant) displayed signs of hesitation, fear, or discomfort. These signs of discomfort could be presented in different ways, such as patients with trypanophobia being hesitant to extend their arm for the procedure, or patients who start crying. The trainer, when taking the role of the phlebotomist, deliberately reacted to the patient’s anxiety by reassuring the patient and calmly asking, “Are you afraid of needles?” Questions like these will show the patient that the phlebotomist is paying attention to his or her anxiety. Then, the trainer further reassured the patient by saying, “I understand that it might be scary, but I’m using this tiny needle, which looks just like a butterfly.” Descriptive and calming statements like these will encourage the patient to recall associated childhood experiences (e.g., the quick and light brushes of butterfly wings). Subsequently, recalling these experiences can make the patients feel reassured that the short time of discomfort they feel is similar to what they remember, and that the procedure will be over quickly.\n\nEliciting performance\n\nAfter the demonstration step was completed, the trainer conducted the performance step of Peyton’s approach. Students then were be divided into groups of three to role-play and practice their communication skills with different types of patients and were instructed to take turns performing as the phlebotomist, patient, and observer. This activity mimicked real work situations and helped students develop effective communication skills. The observers in the scenarios were responsible for witnessing the interactions between the phlebotomist and patient, as well as discussing the phlebotomist’s performance; they prompted discussions to explain what could be improved or done differently. Studies show that this step reveals the importance of role-play as a teaching method as it not only helps mimic real work situations, but also helps students work in teams and develop their communication skills.11\n\nProviding feedback\n\nIn addition to the observer’s feedback in the scenarios, the teaching assistant and trainer observed the students and provided immediate verbal feedback. Feedback, whether positive or negative, is an essential tool in education to help students achieve their maximum potential at any stage of their studies.13 It should be constructive so that students are encouraged to improve their academic development.14 The trainer used the tell, explain, listen, and let’ (TELL model) to provide feedback to students during the role-play performances, which comprises of four main features: tell (tell the students the specific behavior that requires improvement, or compliment them on their good behaviors); explain (offer explanations to show students the outcomes that might occur due to the behaviors demonstrated, whether positive or negative); listen (listen to and allow the students to reflect on the feedback that they have received); and ‘let’ (let the students know about the consequences of their actions if the behaviors are not corrected).14\n\nA common understanding among educators is that feedback is necessary only for the behaviors that require correction. However, feedback that focuses on areas of strength will help build students’ self-confidence and improve their communication with their superiors.15 Overall, this step aimed to help students achieve the learning objective of the session—that is, to develop an effective communication skill set.\n\nAssessing performance\n\nAfter all groups took turns to perform each role and receive feedback, the students were regrouped into pairs. All students took turns to role-play as the phlebotomist and patient, while the teaching assistant and trainer observed how they interact in both roles. A formative assessment was used to evaluate the students’ performances and offered them the opportunity to reflect on and make the necessary adjustments to improve their future learning.16 A graded checklist was used for the assessment and given to the students, so they would be better informed in future when performing the actions related to phlebotomy (see Figure 1).\n\nEnhancing retention and transfer\n\nThe trainer used two methods to help students retain the knowledge that they gained and transfer it to others. First, 15 minutes before the end of the session, the trainer asked students to share their thoughts about the session, what they had learned, and to reflect on their performances. This approach allowed the students to not only retain their knowledge but also learn from the experiences of others. Second, the trainer provided the students their graded assessments to give them the chance to reflect on their performances privately.\n\nFinally, at the end of the session, the facilitator provided a summary of the main learning objectives covered.\n\nAt the end of the session, an online survey was sent to all participants to collect their views on the session. Answers to each question was given on a Likert scale of 1-5, where 5 meant strongly agree and 1 strongly disagree. The questions of the survey were modified from Taniguchi et al to fit the outcomes of the lesson plan.4\n\nThe survey also included an open-ended question section to allow the participants to freely express their thoughts about the session. The open-ended section included three questions:\n\n1. What did you learn from the session?\n\n2. What did you like about the session?\n\n3. What can you suggest to us to improve in the future?\n\nThe survey questions can be found in the Extended data.\n\nThe participants responses to the seven questions on the Likert scale 1-5 were analyzed using Microsoft excel to calculate the mean, median and interquartile ranges. The themes for the open-ended questions were identified in advance and the participants responses were categorized according to the pre-determined themes as follows: learning outcome, effectiveness of teaching strategy and areas for improvement.\n\n\nResults\n\n15 out of 17 participants responded to the survey with a 94% response rate. All participants were females as the CLS and Nursing programs in Imam Abdulrahman bin Faisal University are offered only to females. Most of the participants were of the CLS specialty 93.75%, while only 6.25% were from the nursing specialty.\n\nThe survey questions are displayed in boxplots as seen in Figure 2. Generally, participant showed a high satisfaction to the training session. For example, a detailed question on the effectiveness of the session in teaching communication skills showed a mean score of 4.7 on the scale of 5, where 5 being the highest level of satisfaction.\n\n5: strongly agree, 1: strongly disagree. •outlier value.\n\nQ1: Effectiveness of training session in teaching communication skills\n\nQ2: The video shown was suitable for demonstrating proper communication skills\n\nQ3: The case scenarios sufficiently addressed the communication problems with patients\n\nQ4: Provided an understanding of potential problems arising from blood collection\n\nQ5: Training session taught me patient management skills\n\nQ6: Training session helped me improve my communication skills\n\nQ7: Role-Play helped me improve my communication skills.\n\n10 out of 15 participants shared their thought about the session through answering the open-ended questions. The participants indicated that they learned how to listen and communicate with patients during phlebotomy, how to deal with different type of patients and most importantly to pay attention to detail. One participant said: “I learned possible situations I might be go into. Also how to pay attention to detail, and be transparent with the patient as much as possible.” For the second question on what they liked about the session, the participants commended the creative teaching strategy using role-play as well as the interaction with their fellow participants and trainer demonstrating that they learned from listening to other participants sharing their experiences in phlebotomy “giving the opportunity to hear from everyone, listening to each story everyone had.”\n\nTo improve the session in the future the participants suggested to add more videos and case scenarios for role-play and have a blind selection of role-play scenarios and dedicate more time for the session.\n\n\nDiscussion\n\nIn this study, a lesson plan to teach communication skills in phlebotomy was developed and its effectiveness was assessed by the participants of the study. This session allowed the participants to practice their communication skills specifically during phlebotomy, where the focus of the curriculum in on the procedural skill despite that communicating with the patient is one of the crucial steps in ensuring a successful procedure. Overall, the participants were highly satisfied with the training session.\n\nThe result of this study supports other studies recognizing that incorporating role-play in educational programs is a valuable tool for medical students enabling them to practice multiple skill sets without patient risk.11 Furthermore, the results shows that this type of teaching strategy has a great value to the trainees, it provided them with the opportunity to interact with other participants and learning from their previous experiences. This is important for professional growth as explained by the situated learning theory.9 The participants responses to the open-ended questions addresses three main categories: learning outcome, effectiveness of teaching strategy and areas for improvement. 10 out of the 15 participants responding to the first question indicated that they have learned how to communicate with patients under different situations. This supports that the learning outcome of the session plan has been achieved. The responses on the participants on the effectiveness of teaching strategies supports the use of videos and role-play as an -educational teaching strategy to teach communication skills, which allowed them to be creative in visualizing the different scenarios they may face in the future. Under the category of areas of improvement, the participants suggested to include more role-play scenarios representing not only those with trypanophobia but different types of patients. In addition, to have a blind selection from a collection of scenarios not to limit it to two scenarios and to allow the participants to have a blind pick of multiple scenarios instead of taking turns to play a normal patient and a patient with trypanophobia. These responses could be utilized and invested improving educational curriculums. Various studies have demonstrated the benefits of co-creation of the curriculum, where students are seen as partners in education.17,18\n\nDespite the small number of participants in the study, it highlights the importance of communication skills in medical education as well as the importance of utilizing student’s responses in co-creation of the curriculum.\n\n\nConclusion\n\nIn conclusion, in this study we have showed that Gagne’s instructional design does not only provide a platform for lecture-based lessons but can also be expanded to accommodate lesson planning for a wide range of skills, such as practical, communication, and interpersonal skills. The results also highlight the importance of students in the process of co-creation of the curriculum.\n\n\nData availability\n\nHarvard Dataverse: Using Gagne’s Instructional Design to Teach Communication Skills in Phlebotomy Education through Role-Play. https://doi.org/10.7910/DVN/GTGMGE.19\n\nThis project contains the following underlying data:\n\n- Gange phelebotomy session data.tab\n\nHarvard Dataverse: Using Gagne’s Instructional Design to Teach Communication Skills in Phlebotomy Education through Role-Play. https://doi.org/10.7910/DVN/GTGMGE.19\n\nThis project contains the following extended data.\n\n- Questionnaire phlebotomy education.rtf\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nDue to the ethical and copyright limitations around social media data, the data from YouTube used in this study cannot be disclosed. Briefly, the video demonstrated the interaction between child and a phlebotomist. The child demonstrated her fear from needles by asking the phlebotomist multiple questions about the blood extraction process and was pulling her arm away when the phlebotomist attempted to collect blood from her. The video showed how the phlebotomist communicated positively with the child explaining how the process is performed and trying to ease here worries and explaining to the child the consequences of moving her arm during blood extraction. The Methods section contains detailed information to allow replication of the study. Any queries about the methodology should be directed to the corresponding author.",
"appendix": "Acknowledgments\n\nThe author would like to thank Ms. Ashwaq Al-Amri, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia for her help in running the session. Special thanks goes to Dr. Mohammed Al-Eraky, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia for his valuable review of the manuscript.\n\n\nReferences\n\nStedman TL: Stedman’s medical dictionary for the health professions and nursing. A medical dictionary for the health professions and nursing. 6th ed.Philadelphia, USA: Wolters Kluwer Health; 2008.\n\nMbah HA: Phlebotomy and quality in the African laboratory. Afr J Lab Med. 2014; 3(1): 4–7. PubMed Abstract | Publisher Full Text\n\nRodriguez-Paz JM, Kennedy M, Salas E, et al.: Beyond “see one, do one, teach one:” toward a different training paradigm. Postgrad. Med. J. 2009; 85(1003): 244–249. PubMed Abstract | Publisher Full Text\n\nTaniguchi JI, Matsui K, Araki T, et al.: Clinical training: a simulation program for phlebotomy. BMC Med. Educ. 2008; 8: 7. Publisher Full Text\n\nCunha MLDR, Brandi S, Bonfim GFT, et al.: Application program to prepare child/family for venipuncture: experience report. Rev. Bras. Enferm. 2018; 71(suppl 3): 1474–1478. PubMed Abstract | Publisher Full Text\n\nFilbet M, Larkin P, Chabloz C, et al.: Barriers to venipuncture-induced pain prevention in cancer patients: a qualitative study. BMC Palliat. Care. 2017; 16(1): 5–7. PubMed Abstract | Publisher Full Text\n\nWoo WH: Using Gagne’s instructional model in phlebotomy education. Adv. Med. Educ. Pract. 2016; Volume 7: 511–516. PubMed Abstract | Publisher Full Text\n\nGagné RM, Briggs LJ, Wager WW: Principles of instructional design. Perform. Improv. 2005; 44: 44–46. Publisher Full Text\n\nKnowles M: The adult learner: a neglected species. Houston, Texas: Gulf Publishing Company; 1973 [cited 2021 April 19]; 211. Reference Source\n\nDagar V, Yadav A: Constructivism: a paradigm for teaching and learning. Arts Soc Sci J. 2016; 7(4): 66–70. Publisher Full Text\n\nNestel D, Tierney T: Role-play for medical students learning about communication: guidelines for maximising benefits. BMC Med. Educ. 2007; 7: 3. PubMed Abstract | Publisher Full Text\n\nNikendei C, Huber J, Stiepak J, et al.: Modification of Peyton’s four-step approach for small group teaching—a descriptive study. BMC Med. Educ. 2014; 14(1): 68. PubMed Abstract | Publisher Full Text\n\nHesketh EA, Laidlaw JM: Developing the teaching instinct, 1: feedback. Med. Teach. 2002; 24(3): 245–248. PubMed Abstract | Publisher Full Text\n\nHamid Y, Mahmood S: Understanding constructive feedback: a commitment between teachers and students for academic and professional development. J. Pak. Med. Assoc. 2010; 60(3): 224–227. PubMed Abstract\n\nBrown N, Cooke L: Giving effective feedback to psychiatric trainees. Adv. Psychiatr. Treat. 2009; 15(2): 123–128. Publisher Full Text\n\nMenéndez IYC, Napa MAC, Moreira MLM, et al.: The importance of formative assessment in the learning teaching process. Int J Soc Sci Humanit. 2019; 3(2): 238–249. Publisher Full Text\n\nLubicz-Nawrocka TM: Students as partners in learning and teaching: The benefits of co-creation of the curriculum. International Journal for Students As Partners. 2018; 2(1): 47–63. Publisher Full Text\n\nBovill C, Woolmer C: How conceptualisations of curriculum in higher education influence student-staff co-creation in and of the curriculum. High. Educ. 2019; 78: 407–422. Publisher Full Text\n\nOwaidah A: Using Gagne’s Instructional Design to Teach Communication Skills in Phlebotomy Education through Role-Play, Harvard Dataverse, V1, UNF:6:H0YiVGrIe1LxEYs1fFgEFA== [fileUNF].2021. Publisher Full Text"
}
|
[
{
"id": "146424",
"date": "24 Aug 2022",
"name": "Conor Gilligan",
"expertise": [
"Reviewer Expertise Medical education",
"interactional skills teaching",
"healthcare communication"
],
"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 detailed description of their lesson plan for teaching communication skills associated with phlebotomy. The description of the lesson is clear and each step is well justified.\nThe value of the focus on communication skills associated with phlebotomy is made clear, but the need for this work in terms of the application of Gagne's instructional design to this process is less clearly justified. There is a plethora of literature describing educational interventions for improving medical students' communication skills across diverse medical consultations. The authors could more clearly explain why the communication required during/associated with phlebotomy is unique and why a different teaching approach is required.\nThe authors describe the lesson plan using language that presents the approach as very certainly achieve the desired outcomes. In many cases, these are in fact the intentions of the selected approaches, rather than absolutes.\nThe authors refer learning styles in their 'gaining attention' section - presenting these as though they exist as entirely mutually exclusive ways of learning. Recent literature support the blurring of boundaries between learning styles. The approach used appropriately provides stimuli which will appeal to a range of learning styles and I think it would be useful to emphasize the blurred 'boundaries' between styles.\nI would like to better understand the logistics of the facilitator and teaching assisting observing and providing feedback on student role-plays - how was this managed with multiple groups and pairs conducting role-play at once?\nI'm not sure that a boxplot is the most appropriate format in which to present the data in figure 2 - perhaps a bar graph displaying means would be more clearly illustrative of the point?\nThe limitations of this work need to be acknowledged. There is no measure of behavioural outcome. While it is recognised that such measures are difficult to achieve, it should be acknowledged that in the absence of such measures, the true effectiveness of this session remains unknown.\n\nIs the rationale for developing the new method (or application) clearly explained? Partly\n\nIs the description of the method technically sound? Yes\n\nAre sufficient details provided to allow replication of the method development and its use by others? Yes\n\nIf any results are presented, are all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "8693",
"date": "05 Aug 2024",
"name": "Amani Y. Owaidah",
"role": "Author Response",
"response": "Dear respected reviewer, Thank you for your valuable comments that is highly appreciated. Following are my responses to your comments, to the best of my knowledge, I have addressed all the comments/ clarifications requested. The value of the focus on communication skills associated with phlebotomy is made clear, but the need for this work in terms of the application of Gagne's instructional design to this process is less clearly justified. There is a plethora of literature describing educational interventions for improving medical students' communication skills across diverse medical consultations. The authors could more clearly explain why the communication required during/associated with phlebotomy is unique and why a different teaching approach is required. With phlebotomy, the teaching approach is focused on the procedural skill of withdrawal of blood successfully, which is covered in m any laboratory sessions throughout the educational curriculum, however, with phlebotomy, there is a level of communication with patients/ donors with the phlebotomist. In real-life cases some patients present phobia of needles or anxiety, therefore, the phlebotomist with addition to excellent procedural skills has to have good communication skills to accommodate different types of patients in order to draw blood from them. In the absence of such skills the phlebotomist will not be able to ease patients and fulfill doctors request for testing. The authors describe the lesson plan using language that presents the approach as very certainly achieve the desired outcomes. In many cases, these are in fact the intentions of the selected approaches, rather than absolutes. The authors refer learning styles in their 'gaining attention' section - presenting these as though they exist as entirely mutually exclusive ways of learning. Recent literature support the blurring of boundaries between learning styles. The approach used appropriately provides stimuli which will appeal to a range of learning styles and I think it would be useful to emphasize the blurred 'boundaries' between styles. This is an excellent point to emphasize the different learning styles. However, the focus teaching strategy was not to go into detail on the various learning styles rather than presenting a well-known instructional design for a lesson plan to follow to ensure proper implementation of a new teaching approach. Follow up work could include the behavioral outcome on different cohorts. I would like to better understand the logistics of the facilitator and teaching assisting observing and providing feedback on student role-plays - how was this managed with multiple groups and pairs conducting role-play at once? As the number of students were small. The instructor and teaching assistant moved around the groups while they were practicing their role-play to provide them feedback. In addition, as described in the paper the in the group one student took the role of the observer to observe the other two students. Which one played the patient and the other played the role of the phlebotomist. The observer also provided feedback to their colleagues on their performance. By this methods student gain the skill of peer assessment and raise their sense of self-awareness. I'm not sure that a boxplot is the most appropriate format in which to present the data in figure 2 - perhaps a bar graph displaying means would be more clearly illustrative of the point? The use of boxplots was selected by to present the different quartiles of the analysis. However, if necessary format could be presented in bar graphs. The limitations of this work need to be acknowledged. There is no measure of behavioural outcome. While it is recognised that such measures are difficult to achieve, it should be acknowledged that in the absence of such measures, the true effectiveness of this session remains unknown. I agree, the behavioral outcome should be assessed to measure the true effectiveness of the session. However, However, the focus teaching strategy presenting a well-known instructional design for a lesson plan to follow to ensure proper implementation of a new teaching approach. Follow up work could include the behavioral outcome on different cohorts. Also could include feedback from clinical instructors to provide feedback on the effectiveness of this teaching method. The outcome of the current paper could be used to improve the design of the current curriculum by providing the students with the opportunity to co-create the curriculum. Looking forward to hearing from you"
}
]
},
{
"id": "201322",
"date": "12 Sep 2023",
"name": "Modibo Coulibaly",
"expertise": [
"Reviewer Expertise Clinical Biochemistry"
],
"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\nCongratulations to the author of this paper. The manuscript is reasonably well written according to the scientific writing and meets the journal's requirements. In this paper, the author tried to emphasize the communication aspect in teaching phlebotomy through Gagne's pedagogical design and using role-playing games. This method adds a new skill to the routine of practitioners who had benefited from training focused on technical and procedural aspects.\nThe implementation of this practice could contribute to improving the quality of patient care while focusing on their needs. The topic of this paper is in line with the scope of F1000research and would add value to scientific production.\nHowever, it contains some weaknesses that should be fixed.\nThe term \"blood extraction\" is not too suitable. It should, therefore, be replaced by “blood draw” or “blood collection.”\nThe author should give more detail on the study population by explaining why clinical laboratory sciences are offered only to women in his country.\nRegarding selecting participants, the author only announced that e-mails were sent to students and residents without specifying the number to which the e-mails were sent. So, it's difficult to determine the response rate and discuss other invitation methods, such as physically meeting to find participants.\nAs worded in the paper, the response rate needs to be clarified. Did the ratio of 15 to 17 obtain it? In this case, the response rate is 88.2% instead of 94%. Thank you for specifying.\nThe study concerns only trypanophobia, while there may be other phobias during phlebotomy, such as hematophobia1, hypochondriacal patients2, and nosocomephobia3. To better understand the fundamental concern of patients when they appear anxious, the question to ask these patients must be an open question in the style of \"What are you afraid of\", instead of \"Are you afraid of the needle\"?\nMoreover, the role-play does not allow us to appreciate the real cognitive behavioral perceptions of the actual patients who could have particular intrinsic characteristics whose reflection on the solutions could improve the educational program.\nAs indicated by the participants to include other types of patients, it would be relevant at this level to have patients of pediatric age. These evoke the double challenge and stress condition for the patient and the phlebotomist, given the difficulty of sampling in this category of patients.\nThese conditions can only be assessed by associating a practical phase with real adult and child patients, inpatients, and outpatients.\nFinally, I suggest the author discuss integrating communication skills with the new approach to phlebotomy automation. Today, miniaturized sampling systems are based on combining ultrasound images, robotics, and artificial intelligence. Incorporating communication skills into these automated systems that perform safe and precise venous sampling would be a disruptive innovation in the sciences of phlebotomy4.\n\nIs the rationale for developing the new method (or application) clearly explained? Yes\n\nIs the description of the method technically sound? Yes\n\nAre sufficient details provided to allow replication of the method development and its use by others? Yes\n\nIf any results are presented, are all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "12100",
"date": "05 Aug 2024",
"name": "Amani Y. Owaidah",
"role": "Author Response",
"response": "Dear Respected reviewer, Thank you very much for your valuable comments and feedback on our paper. Below is the response to each point you have raised. Looking forward to hearing from you in order to change version 2 accordingly. The term \"blood extraction\" is not too suitable. It should, therefore, be replaced by “blood draw” or “blood collection.” The terms blood extraction are used interchangeably in laboratory sciences with blood collection. However, the term is a matter of preference rather than an incorrect scientific term. It will be changed in version 2 to Blood collection based on your comments The author should give more detail on the study population by explaining why clinical laboratory sciences are offered only to women in his country. In the university where the study was conducted the program is offered to only female as low enrollment rate were found in males so due to financial reasons the male section was closed. Regarding selecting participants, the author only announced that e-mails were sent to students and residents without specifying the number to which the e-mails were sent. So, it's difficult to determine the response rate and discuss other invitation methods, such as physically meeting to find participants. As worded in the paper, the response rate needs to be clarified. Did the ratio of 15 to 17 obtain it? In this case, the response rate is 88.2% instead of 94%. Thank you for specifying. Thank you for pointing out the typo in the response rate. Indeed it is 88.2%. This will be changed accordingly. Yes, emails were the only method used to communicate with the participants. As mentioned in the paper that only level 4 students were invited to participate in the study therefore the emails of level 4 students was not difficult to track as the number of registered students are in the university’s data base. The study concerns only trypanophobia, while there may be other phobias during phlebotomy, such as hematophobia1, hypochondriacal patients2, and nosocomephobia3. To better understand the fundamental concern of patients when they appear anxious, the question to ask these patients must be an open question in the style of \"What are you afraid of\", instead of \"Are you afraid of the needle\"? Thank you for suggesting other phobias. In the paper the author mentions trypanophobia as just an example which is the most commonly encountered. And the phrase “Are you afraid of the needle\"? Is used as a conversation opener rather than specifying a type of phobia. But this comment will be taken for future lessons. Moreover, the role-play does not allow us to appreciate the real cognitive behavioral perceptions of the actual patients who could have particular intrinsic characteristics whose reflection on the solutions could improve the educational program. Role play does not assess the behaviour of actual patients. It is used only as a preliminary teaching methods for students practice. Simulation with real patients is definitely the next step in teaching to assess the real behavioral perceptions. But for the level of the students and administrative limitations simulations could not be used but could be a future study, As indicated by the participants to include other types of patients, it would be relevant at this level to have patients of pediatric age. These evoke the double challenge and stress condition for the patient and the phlebotomist, given the difficulty of sampling in this category of patients. These conditions can only be assessed by associating a practical phase with real adult and child patients, inpatients, and outpatients. Agreed. As in the previous comment simulation with real patients could be a future study to conduct. Also, the reviewer could appreciate pediatric patients require a wide range of administrative process such as parental consent and IRB for involvement in a study. In addition the focus of the paper was for to use a different teaching strategy to just a procedural skill of blood collection. To help students improve their communication skills and teach them how to deal with different situations rather than just a procedure. Finally, I suggest the author discuss integrating communication skills with the new approach to phlebotomy automation. Today, miniaturized sampling systems are based on combining ultrasound images, robotics, and artificial intelligence. Incorporating communication skills into these automated systems that perform safe and precise venous sampling would be a disruptive innovation in the sciences of phlebotomy4. This is an excellent point to consider for the future. However , these methods help in teaching procedural skills and the focus of our paper was communication skills. This point could be a focus of another paper using advanced methodologies to teach phlebotomy."
}
]
},
{
"id": "201321",
"date": "02 Oct 2023",
"name": "Ilona Heldal",
"expertise": [
"Reviewer Expertise Information systems. We have several projects on digital support of learning phlebotomy in various medical education."
],
"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 paper explains the importance of explicitly utilizing a structured method (Gagne’s instructional design) for practicing communication and, within this, role-playing for learning phlebotomy. While the issue is important in many educational situations, unfortunately, I cannot suggest the paper for indexing. The aim is important, but it is difficult to understand the added value of the paper.\n\nAs the authors stated, it is vital to understand and learn how to practice communication skills in education, preparing students to deal with patients. Much of the obligatory moments are usually included in the procedural learning parts. Accordingly, I do not agree with “Lesson planning in phlebotomy education is mainly focused on procedural skills, and very little attention is given towards teaching communication skills despite the close patient interaction in phlebotomy.” Stated in the abstract. Additionally, the paper shows many similarities with the cited paper from Woo (Woo, W.H., 2016. Using Gagne’s instructional model in phlebotomy education. Advances in medical education and practice, pp.511-516.) without explaining fundamental differences from it.\nIf the authors would like to index the paper, I suggest improving it by explicitly describing procedural learning, what within this learning can be achieved by Gagne’s method, and within this, again, how role-playing is important and planned. Here is a must to differentiate this study from Woo’s. Also, focusing on role-playing particularities, if the role-playing effect can be explicitly described and specificities of this case resulting in changes in student behavior would be a necessity.\n\nIs the rationale for developing the new method (or application) clearly explained? No\n\nIs the description of the method technically sound? No\n\nAre sufficient details provided to allow replication of the method development and its use by others? Yes\n\nIf any results are presented, are all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-46
|
https://f1000research.com/articles/13-647/v1
|
17 Jun 24
|
{
"type": "Policy Brief",
"title": "Incorporating basic periodontal screening into antenatal care services provided in Rwanda: A policy brief",
"authors": [
"Peace Uwambaye",
"Kehinde Kazeem Kanmodi",
"Kehinde Kazeem Kanmodi"
],
"abstract": "Background Preterm birth, which is child delivery before 37 weeks of pregnancy, is the primary cause of perinatal mortality worldwide. Preterm birth remains a major public health challenge in Rwanda, affecting approximately 13.8% of birth. The World Health Organization estimates that 15 million babies are born prematurely each year. While the association between periodontitis and preterm deliveries is increasingly recognized, little is known about this link in Rwanda. This policy brief aims to bridge this knowledge gap by presenting the findings of a recent study investigating the prevalence of periodontitis among pregnant women in Rwanda and its association with preterm deliveries. This policy brief also aims to inform and guide decision making towards incorporating periodontal screening into the antenatal care package in Rwanda. This has the potential to improve pregnancy outcomes and contribute to improved oral health in the future.\n\nPolicy outcome and Implications Contemporary evidence has shown a six-fold increased risk of preterm delivery for women with periodontitis in Rwanda, with a concerningly high prevalence (60%) among pregnant women. Additionally, nurses working in antenatal clinics displayed insufficient knowledge about gum disease.\n\nActionable recommendations The adoption of basic periodontal screening within existing antenatal care packages is recommended. This, coupled with nurse training and public awareness campaigns, can empower women and healthcare professionals to prioritize oral health for better pregnancy outcomes.\n\nConclusions Integrating periodontal screening into antenatal care has the potential to significantly reduce preterm deliveries and contribute to a healthier future generation in Rwanda.",
"keywords": [
"Antenatal care",
"periodontitis",
"preterm birth",
"preterm deliveries",
"policy brief",
"Rwanda"
],
"content": "Background\n\nPreterm birth, which is child delivery before 37 weeks of pregnancy, is the primary cause of perinatal mortality worldwide. It remains a major public health concern in Rwanda, affecting approximately 13.8% of birth.1 The World Health Organization estimates that 15 million babies are born prematurely each year.1 Periodontitis is a chronic inflammatory disease of the gums that can lead to tooth loss. It is one of the most common chronic diseases in the world, affecting nearly half of all adults. Periodontitis is also a risk factor for preterm delivery, which is defined as delivery before 37 weeks of pregnancy.2,3\n\nWhile the association between periodontitis and preterm deliveries is increasingly recognized, little is known about this link in Rwanda. This policy brief aims to bridge this knowledge gap by presenting the findings of a recent study investigating the prevalence of periodontitis among pregnant women in Rwanda and its association with preterm deliveries. This policy brief also aims to inform and guide decision making towards incorporating periodontal screening into the antenatal care package in Rwanda. This has the potential to improve pregnancy outcomes and contribute to improved oral health in the future.\n\n\nPolicy outcomes and implications\n\nDifferent studies have suggested a complex link between periodontitis and preterm birth. Chronic inflammation in the gums associated with periodontitis releases inflammatory mediators into the blood stream and this potentially triggers early labor through various biomedical pathways.4-7 Also, oral bacteria from infected gums can reach the placenta and amniotic fluid, triggering an inflammatory response in the uterus and inducing preterm labor.8,9 Also, periodontitis can impair nutrient absorption, impacting fetal growth and development which may contribute to preterm birth.10 Periodontal diseases occur as result of dysbiosis in bacterial biofilm inhabiting the sulcus, below the gingival margin. Periodontal are inclusive of the main diagnostic categories of periodontitis and gingivitis.6,7,11\n\nExisting research from Rwanda, like some other African countries, demonstrates a significant association between periodontitis and preterm birth. A study in Kenya reported that women with periodontitis have 2 times risk of giving birth to preterm babies than women without periodontitis.12 In Ethiopia, a study reported 2-4 times the odds of giving birth to preterm babies in women with periodontitis13 while in Rwanda is six-fold risk of preterm in women with periodontitis than those with no periodontitis.14\n\nA recent study in Rwanda showed a high prevalence of periodontitis (60.5%) among pregnant women and a six-fold risk of preterm deliveries in women who had periodontitis.14 Further, nurses and midwives showed an insufficient knowledge on periodontitis.15 There is a need fora tool to support the nurses/midwives to detect periodontal diseases among pregnant women during antenatal care consultations.\n\nPeriodontal screening is not currently part of the antenatal care package in Rwanda, despite the increasing prevalence of periodontitis among pregnant women in Rwanda. Research evidence has shown the strong association between periodontitis and preterm birth.14 Several studies confirm that the treatment of periodontitis during pregnancy reduces the risk of preterm delivery.\n\nAntenatal care consultations constitute an important opportunity to perform screening for periodontitis during pregnancy in the context of Rwanda. Firstly, antenatal care consultations are mandatory for all pregnant women. Secondly, the uptake is high (98%) and a greater number of pregnant women meet the required number of antenatal care visits.16\n\nThe increasing uptake of antenatal care services in Rwanda is supported by more comprehensive medical insurance schemes (e.g “Mutuel de Sante” that covers 85% of the cost). Community health workers (CHWs) identify all pregnant women in their villages and follow them up until delivery. CHWs ensure that these pregnant women attend antenatal care.\n\nOral diseases, including periodontitis, are neglected and it is rare for a woman to go for dental check-ups unless when in pain. Antenatal care is an important platform that offers the opportunity to bring awareness on periodontitis during pregnancy. Periodontitis screening during antenatal care consultations will facilitate the access of all pregnant women to oral health.\n\nThis policy brief calls for action for the development of a screening tool and sustainable implementation of this tool. Thus, the development of a periodontal screening tool that can be utilized and integrated in an antenatal care package would be desirable and cost-effective. If a robust screening tool is successfully developed, then future studies may include the management of periodontitis during pregnancy and its effect on preterm delivery.\n\n\nActionable recommendations\n\nTo address the potential link between periodontitis and preterm birth in Rwanda, multiple recommendations are proposed. Some of these recommendations were raised during the policy engagement workshop that was held, and led by the lead author of this policy brief, in October 2024 where there was a presentation of the study findings to different policy makers and partners that included professional associations, representatives from hospitals and representatives from Rwanda Ministry of Health through the Rwanda Biomedical Center. These recommendations are below:\n\nThe incorporation of Periodontal Screening in Antenatal Care: There is a need to integrate a basic periodontal screening into the existing Rwandan ANC package. This screening can be performed by trained nurses and could involve visual inspection and probing to identify signs of gum inflammation and potential periodontitis. This can be done by developing clear protocols and guidelines for nurses on how to conduct the screening, interpret results, and refer women with suspected periodontitis to dentists for further evaluation and treatment.\n\nCapacity Building for Nurses: There is need to implement training programs to equip nurses working in antenatal clinics with the knowledge and skills to effectively: conduct basic periodontal screenings, educate pregnant women about oral hygiene practices and the link between gum health and pregnancy outcomes and advise women on appropriate referrals for periodontal treatment when necessary.\n\nPublic Awareness Campaigns: There is a need to develop and disseminate public awareness campaigns to educate women of childbearing age about periodontal disease, its risks during pregnancy, and the importance of maintaining good oral hygiene.\n\n\nConclusion\n\nWhile the causal relationship between periodontitis and preterm birth requires further investigation, the existing evidence suggests a potentially significant link. By integrating oral health into maternal care, promoting oral hygiene practices, and conducting further research, we can take crucial steps to address this issue and improve maternal and child health outcomes in Rwanda. Policymakers, healthcare professionals, and community leaders in Rwanda should recognize the potential impact of periodontitis on preterm birth. By implementing the recommended actions and prioritizing oral health promotion, we can work together to ensure mothers and babies have a healthy start in life.\n\n\nAuthor contributions\n\nBoth authors (PU and KK) contributed to writing of the original draft, reviewing, editing and conceptualization of the manuscript.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data and software availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nNil.\n\n\nReferences\n\nRutayisire E, Mochama M, Ntihabose CK, et al.: Maternal, obstetric and gynecological factors associated with preterm birth in Rwanda: findings from a national longitudinal study. BMC Pregnancy Childbirth. 2023; 23(1): 1–10. Publisher Full Text\n\nShewale AH, Gattani DR, Bhatia N, et al.: Prevalence of periodontal disease in the general population of India-A systematic review. J. Clin. Diagn. Res. 2016; 10: ZE04–ZE09. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEke PI, Dye BA, Wei L, et al.: Prevalence of Periodontitis in Adults in the United States: 2009 and 2010. J. Dent. Res. 2012 Oct 30 [cited 2018 Jun 20]; 91(10): 914–920. Publisher Full Text\n\nScannapieco FA, Bush RB, Paju S, et al.: Periodontal Disease as a Risk Factor for Adverse Pregnancy Outcomes. A Systematic Review. Ann Periodontol. 2003 [cited 2017 Jun 7]; 8: 70–8. PubMed Abstract | Publisher Full Text Reference Source\n\nHaerian-Ardakani A, Eslami Z, Rashidi-Meibodi F, et al.: Relationship between maternal periodontal disease and low birth weight babies. Iran. J. Reprod. Med. 2013 Aug [cited 2017 Aug 8]; 11(8): 625–630. Reference Source\n\nBobetsis YA, Graziani F, Gürsoy M, et al.: Periodontal disease and adverse pregnancy outcomes. Periodontol. 2020 Jun 8 [cited 2020 Aug 5]; 83(1): 154–174. Publisher Full Text\n\nUwambaye P, Munyanshongore C, Rulisa S, et al.: Assessing the association between periodontitis and premature birth: a case-control study. BMC Pregnancy Childbirth. 2021; 21(1): 1–9. Publisher Full Text\n\nWang YL, Liou JD, Pan WL: Association between maternal periodontal disease and preterm delivery and low birth weight. Taiwan. J. Obstet. Gynecol. 2013; 52(1): 71–76. Publisher Full Text\n\nLee YL, Hu HY, Chou SY, et al.: Periodontal disease and preterm delivery: a nationwide population-based cohort study of Taiwan. Sci. Rep. 2022; 12(1): 3297–3299. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNascimento M, Silva D, Ribeiro S, et al.: Effect of a nutritional intervention in athlete’s body composition, eating behaviour and nutritional knowledge: A comparison between adults and adolescents. Nutrients. 2016; 8(9): 1–14. Publisher Full Text\n\nJajoo NS, Shelke AU, Bajaj RS, et al.: Association of periodontitis with pre term low birth weight – A review. Placenta. W.B. Saunders Ltd; 2020; vol. 95. : 62–68.\n\nShaggag LM, Alhabardi N, Adam I: The Association between Maternal Periodontitis and Preterm Birth: A Case-Control Study in a Low-Resource Setting in Sudan, Africa. Med. 2022; 58(5). Publisher Full Text\n\nTeshome A, Yitayeh A: Relationship between periodontal disease and preterm low birth weight: Systematic review. Pan Afr. Med. J. 2016; 24: 1–10.\n\nUwambaye P, Kerr M, Rulisa S, et al.: Prevalence of Periodontitis and Associated Factors among Pregnant Women: A cross sectional survey in Southern Province. Rwanda. Rwanda J Med Heal Sci. 2021; 4(1): 131–150. Publisher Full Text\n\nUwambaye P, Munyanshongore C, Kerr M, et al.: Assessment of the knowledge, attitude and practices of nurses and midwives working at antenatal clinics in the southern province of Rwanda on periodontal diseases: A cross-sectional survey. Adv. Med. Educ. Pract. 2020; 11: 517–523. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDusingizimana T, Ramilan T, Weber JL, et al.: Predictors for achieving adequate antenatal care visits during pregnancy: a cross-sectional study in rural Northwest Rwanda. BMC Pregnancy Childbirth. 2023; 23(1): 69–69. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "294152",
"date": "03 Jul 2024",
"name": "Jaume Miranda-Rius",
"expertise": [
"Reviewer Expertise Periodontology and 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\nDear Authors,\nI enjoyed reading this manuscript. Especially in countries where there is a shortage of dental surgeons it is important to involve nurses in oral health education. Maternity is important in women's lives so midwives need to acquire knowledge about periodontitis and its possible repercussions on the foeto-placental unit.\n\nPerhaps I could suggest to the authors to add these three references as they are studies also carried out in East Africa.\n\nGesase N, et. al., 2018 (Ref 1)\nMiranda-Rius J, et. al., 2023 (Ref 2)\nColeman M, et. al., 2019 (Ref 3)\nMinor Revision:\nCOMMENTS TO THE DOCUMENT INCORPORATING BASIC SCREENING INTO ANTENATAL CARE SERVICES PROVIDED IN RWANDA: A POLICY BRIEF Peace Uwambaye, Kehinde Kazeem Kanmodi (2024)\nThis is a brief policy brief on the issue of preterm births in Rwanda. It has been shown that the rate of these births is very high. Simultaneously, several studies have found periodontitis to be a risk factor for preterm birth (<37 weeks). The aim of this study is to assess the prevalence of periodontitis in the country and to recommend a social policy of periodontitis control in pregnant women: diagnosis and prenatal care to reduce it and decrease the incidence of preterm births.\n\nSome objectives to be commented on:\n\n--In section \"Policy outcomes and implications\", 4th paragraph, last line, there is a reference to some studies but the citations of these studies are not given. They should be referenced.\n\n-- It is said that periodontal screening should be carried out on pregnant women to find out their periodontal situation, and from there to apply statistics, records and treatment; but it is not explained how this is to be carried out. No action plan is specified. It is only recommended to implement actions to prioritise oral health and to establish joint boundaries between specialties. Therefore, it will be good to start from this document a prospective cohort study design, in order to present guidelines to the Ministry of Health.\n\nDoes the paper provide a comprehensive overview of the policy and the context of its implementation in a way which is accessible to a general reader? Yes\n\nIs the discussion on the implications clearly and accurately presented and does it cite the current literature? No\n\nAre the recommendations made clear, balanced, and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "12101",
"date": "05 Aug 2024",
"name": "Peace UWAMBAYE",
"role": "Author Response",
"response": "REVIEWER 1 Dear Authors, I enjoyed reading this manuscript. Especially in countries where there is a shortage of dental surgeons it is important to involve nurses in oral health education. Maternity is important in women's lives so midwives need to acquire knowledge about periodontitis and its possible repercussions on the foeto-placental unit. Response: Thank you. REVIEWER 1: Perhaps I could suggest to the authors to add these three references as they are studies also carried out in East Africa. Gesase N, et. al., 2018 (Ref 1) Miranda-Rius J, et. al., 2023 (Ref 2) Coleman M, et. al., 2019 (Ref 3) Response: Thank you. We have now cited these three references in the revised manuscript. REVIEWER 1: This is a brief policy brief on the issue of preterm births in Rwanda. It has been shown that the rate of these births is very high. Simultaneously, several studies have found periodontitis to be a risk factor for preterm birth (<37 weeks). The aim of this study is to assess the prevalence of periodontitis in the country and to recommend a social policy of periodontitis control in pregnant women: diagnosis and prenatal care to reduce it and decrease the incidence of preterm births. Some objectives to be commented on: --In section \"Policy outcomes and implications\", 4th paragraph, last line, there is a reference to some studies but the citations of these studies are not given. They should be referenced. Response: Thank you. We have now provided references to support this sentence. We cited the three references you recommended as well as the two references recommended by Reviewer 2. Reviewer 1: It is said that periodontal screening should be carried out on pregnant women to find out their periodontal situation, and from there to apply statistics, records and treatment; but it is not explained how this is to be carried out. No action plan is specified. It is only recommended to implement actions to prioritise oral health and to establish joint boundaries between specialties. Therefore, it will be good to start from this document a prospective cohort study design, in order to present guidelines to the Ministry of Health. Response: Thank you. We would like to avoid being too specific by saying that a prospective cohort study design should be conducted in our recommendations, because all research investigations should be welcome by the government on this area. However, this we will put at the back of our mind. We will be very glad to pursue a research project on that and we are very open to collaborative opportunities. Reviewer 1- References: 1. Gesase N, Miranda-Rius J, Brunet-Llobet L, Lahor-Soler E, et al.: The association between periodontal disease and adverse pregnancy outcomes in Northern Tanzania: a cross-sectional study.Afr Health Sci. 2018; 18 (3): 601-611 PubMed Abstract | Publisher Full Text 2. Miranda-Rius J, Brunet-Llobet L, Blanc V, Álvarez G, et al.: Microbial profile of placentas from Tanzanian mothers with adverse pregnancy outcomes and periodontitis.Oral Dis. 2023; 29 (2): 772-785 PubMed Abstract | Publisher Full Text 3. M, Coleman A, Orvis S, Merillat J, et al.: Inhibition of the Chemokine Response Prevents Preterm Labor but Not an Invasive Infection in a Nonhuman Primate Model. https://link.springer.com/article/10.1177/1933719119834079?utm_source. 2019. Response: Thank you. We have now cited these three references in the revised manuscript."
}
]
},
{
"id": "298808",
"date": "22 Jul 2024",
"name": "Juliana Velosa-Porras",
"expertise": [
"Reviewer Expertise Clinical Epidemiology",
"Epidemiology",
"Periodontics",
"Periodontal disease and its relationship to systemic diseases",
"pregnancy and 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\nDear Authors,\nIt was a pleasure for me to read your manuscript. The research topic is of interest, countries with limited resources should incorporate these strategies to promote oral health and prevent diseases such as preterm birth. As the first point of contact with patients, this manuscript shows the fundamental role of nurses and midwives in the prevention of oral diseases.\nMinor revision\nI suggest this two references:\nPockpa ZAD, et. al., 2022 (Ref 1) Muwazi L, et. al., 2014 (Ref 2)\nBackground\nI suggest that sentences 1 and 6 in the first paragraph could be synthesized – the information is the same.\nPolicy outcomes and implications\nPlease check the wording in the last sentence of the first paragraph.\nI suggest that the second paragraph focus on the association of periodontitis and preterm birth. In the third paragraph the information on the association of periodontitis and preterm birth is unnecessary. Third paragraph, line 3 – \" There is a need fora tool to support the nurses/midwives to detect periodontal diseases among pregnant women during antenatal care consultations.…\" Please check the wording.\nActionable recommendations\nFirst paragraph, line 2 – \" ….. the lead author of this policy brief, in October 2024 where there…..” Please check the wording. Please check this date, since it has not yet passed, I believe it was a typing error.\n\nDoes the paper provide a comprehensive overview of the policy and the context of its implementation in a way which is accessible to a general reader? Yes\n\nIs the discussion on the implications clearly and accurately presented and does it cite the current literature? No\n\nAre the recommendations made clear, balanced, and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "12102",
"date": "05 Aug 2024",
"name": "Peace UWAMBAYE",
"role": "Author Response",
"response": "REVIEWER 2 Dear Authors, It was a pleasure for me to read your manuscript. The research topic is of interest, countries with limited resources should incorporate these strategies to promote oral health and prevent diseases such as preterm birth. As the first point of contact with patients, this manuscript shows the fundamental role of nurses and midwives in the prevention of oral diseases. Minor revision I suggest this two references: Pockpa ZAD, et. al., 2022 (Ref 1) Muwazi L, et. al., 2014 (Ref 2) Response: Thank you. We have now cited these two references in the revised manuscript. Reviewer 2- Background: I suggest that sentences 1 and 6 in the first paragraph could be synthesized – the information is the same. Response: Thank you. Both sentences have now been synthesized. Reviewer 2- Policy outcomes and implications: Please check the wording in the last sentence of the first paragraph. Response: Thank you. This sentence has now been revised. Reviewer 2: I suggest that the second paragraph focus on the association of periodontitis and preterm birth. In the third paragraph the information on the association of periodontitis and preterm birth is unnecessary. Response: Thank you. This sentence, and paragraph, has now been revised. Reviewer 2: Third paragraph, line 3 – \" There is a need fora tool to support the nurses/midwives to detect periodontal diseases among pregnant women during antenatal care consultations.…\" Please check the wording. Response: Thank you. This sentence has now been revised. Reviewer 2- Actionable recommendations: First paragraph, line 2 – \" ….. the lead author of this policy brief, in October 2024 where there…..” Please check the wording. Please check this date, since it has not yet passed, I believe it was a typing error. Response: Thank you. This sentence has now been revised. Reviewer 2- References: 1. Pockpa ZAD, Soueidan A, Koffi-Coulibaly NT, Mobio GS, et al.: Association Between Periodontitis and Preterm Birth in a Cohort of Pregnant Women in Ivory Coast.Oral Health Prev Dent. 2022; 20 (1): 363-368 PubMed Abstract | Publisher Full Text 2. Muwazi L, Rwenyonyi CM, Nkamba M, Kutesa A, et al.: Periodontal conditions, low birth weight and preterm birth among postpartum mothers in two tertiary health facilities in Uganda.BMC Oral Health. 2014; 14: 42 PubMed Abstract | Publisher Full Text Response: Thank you. We have now cited these two references in the revised manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/13-647
|
https://f1000research.com/articles/13-885/v1
|
05 Aug 24
|
{
"type": "Systematic Review",
"title": "Treatment options applied to the preclinical studies using animal models for Chagas Disease: a systematic review and meta-analysis",
"authors": [
"Laura Yesenia Machaca-Luque",
"Mayron Antonio Candia-Puma",
"Brychs Milagros Roque-Pumahuanca",
"Haruna Luz Barazorda-Ccahuana",
"Luis Daniel Goyzueta-Mamani",
"Alexsandro Sobreira Galdino",
"Ricardo Andrez Machado-de-Ávila",
"Rodolfo Cordeiro Cordeiro Giunchetti",
"Eduardo Antonio Ferraz Coelho",
"Miguel Angel Chavez-Fumagalli",
"Laura Yesenia Machaca-Luque",
"Mayron Antonio Candia-Puma",
"Brychs Milagros Roque-Pumahuanca",
"Haruna Luz Barazorda-Ccahuana",
"Luis Daniel Goyzueta-Mamani",
"Alexsandro Sobreira Galdino",
"Ricardo Andrez Machado-de-Ávila",
"Rodolfo Cordeiro Cordeiro Giunchetti",
"Eduardo Antonio Ferraz Coelho"
],
"abstract": "Background Chagas disease (CD) is a neglected tropical disease endemic to Latin America, has emerged as a global health concern due to the migration of infected individuals. With its epidemiological complexity, by difficulty to obtain appropriate diagnoses and poor treatment, the search for novel therapeutic options remains.\n\nMethods In this context, we conducted a systematic review and meta-analysis of preclinical studies employing animal models to verify the progress in CD treatment. We searched the PubMed database for CD treatment studies published between 1990 and 2023, adhering to the PRISMA guidelines.\n\nResults Twelve papers met the inclusion criteria. The findings indicate that the fifteen treatment alternatives examined, mainly between 2010 and 2014, demonstrated efficacy in experimental CD models, evidenced by significant parasitemia reduction. Bis-triazole DO870 and VNI were effective in the acute and chronic phases, respectively. However, of these emerging therapies, only posaconazole and fexinidazole have progressed to clinical trials, yielding unsatisfactory outcomes as CD monotherapies\n\nConclusions This meta-analysis highlights the existence of promising new drug candidates for CD treatment, but most remain in the preclinical stages. Those that reached clinical trials did not demonstrate optimal results, underscoring the ongoing challenges in CD therapy. Collaborative efforts among the academic community, pharmaceutical industries, funding agencies, and government agencies are urgently needed to accelerate the development of more effective medications against CD.\n\nInplasy registration INPLASY202430101 (25/03/2024)",
"keywords": [
"Chagas disease",
"treatment",
"efficacy",
"systematic review",
"meta-analysis",
"parasitemia",
"preclinical studies"
],
"content": "Introduction\n\nChagas Disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected tropical illness endemic to Latin America, predominantly impacting rural and impoverished communities.1 Worldwide, the disease affects an estimated 6 to 7 million people, with 10,000 deaths each year.2 Additionally, there are emerging reports indicating the spread of Chagas Disease to non-endemic countries, fueled by factors such as human migration, travel patterns, globalization, and climate change, thereby introducing new complexities to disease management and surveillance efforts.3 The disease presents two distinct clinic phases: acute and chronic. Acute CD is often characterized by nonspecific symptoms such as fever, malaise, and local edema at the site of parasite entry,4 while chronic infection potentially lead to serious cardiac and gastrointestinal problems such as megaesophagus, megacolon, arrhythmias, and cardiomyopathy. All of these complications further increase the risk of sickness and death.5 The pathogenesis of CD is a complex process, with numerous factors affecting its transmission and spread (e.g., low disease occurrence in dogs or stray animals). In order to effectively combat this disease after so many years, a number of factors, including poor sanitation, shared housing, and what are known as “epidemiological blind spots”, must be properly taken into consideration.6,7 Chronic infections can remain asymptomatic for years, only becoming aware whenever patients are infected even further. This makes infection control and patient care difficult problems indeed. Thus, there is an urgent need for new creative solutions to protect us from what constitutes an ongoing public health challenge.8\n\nThe current therapeutic options for CD mostly consist of two nitroheterocyclic compounds, such as benznidazole and nifurtimox, developed in the late 1960s and early 1970s, respectively.9,10 Despite their decades-long employment, the medications offer limited efficacy, especially in the chronic phase of the disease, and are associated with significant side effects that often necessitate extensive treatment courses.11 The management of CD is further plagued by difficulties stemming from low patient adherence, drug outdating, drug resistance, and therapeutic failure associated with existing therapies.8,11 The development of new drugs for CD has been hampered by various factors, including the lack of financial incentives for pharmaceutical companies to develop drugs for a disease that mainly affects impoverished populations in low-resource settings and the complex biology of the parasite and host immune responses.12,13 Not surprisingly, there is an unmet need for innovative research initiatives and for more effective collaborations that will address the numerous therapeutic challenges posed by CD and improve the number of patients with this disease.14,15\n\nRecently, fundamental research, particularly in the preclinical stage, has been the focal point of efforts aimed at developing new treatment strategies for CD. These endeavors predominantly utilize techniques derived from in vitro or animal investigations.10,16 Notably, animal model-based preclinical research has emerged as indispensable for evaluating novel CD treatment approaches.17 Such studies facilitate the exploration of fundamental mechanisms of action and pharmacokinetic characteristics, while also providing valuable insights into the safety and efficacy of innovative therapies.18 In light of these advancements, the current study aims to conduct a systematic review and meta-analysis of preclinical research utilizing animal models, with the objective of assessing the efficacy of treatment options for CD.\n\n\nMethods\n\nThis systematic review conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (Table S1).19 With registration number INPLASY202430101 and DOI: 10.37766/inplasy2024.3.0101, the protocol for this systematic review was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) website. The entire protocol is accessible at inplasy.com (https://inplasy.com/inplasy-2024-3-0101/).\n\nThe literature was searched for phrases about CD therapy using the MeSH (Medical Subject Headings) term “Chagas Disease”. Using the VOSviewer program (version 1.6.20), the findings were shown in a network diagram showing the co-occurrence of MeSH keywords.20 We looked at clusters in the network map to choose phrases associated with CD therapy. Furthermore, a second round of searches was carried out by linking each MeSH term identified in the cluster analysis with the MeSH terms “Chagas Disease” and “Treatment Outcome”, which relate to assessing the outcomes of interventions used to combat diseases and determining their efficacy,21 For the years 1990–2023, records were obtained from the bibliographic database PubMed (https://pubmed.ncbi.nlm.nih.gov/, last accessed 24 May 2023).\n\nThe procedure for selecting studies for this review comprised three separate phases. During the initial identification phase, only animal studies published between 1990 and 2023 were taken into account. Duplicate articles, non-English publications, reviews, and meta-analyses were excluded at this stage. The subsequent screening phase involved checking the titles and abstracts of the identified articles, and in the eligibility/qualification phase, full-text studies highly relevant to the research question were retrieved, specifically focusing on treatment options for CD. Data on the type of compound used for treatment, dosage, duration of treatment, total sample size, number and species of experimental animals infected with T. cruzi, phase of CD, T. cruzi strain, sample type, and description of the controls were extracted from each of the chosen studies. Studies with insufficient data were excluded. In contrast, those that assessed the effectiveness of therapy by disclosing parasitemia data were retained, considering a 70% decrease in parasitemia as a positive treatment for both the treated and control groups. Options for treatment that included a drug in addition to a conventional CD medication, like nifurtimox or benznidazole, weren’t included. Drugs used in monotherapy were emphasized to confirm which ones show higher effectiveness. WebPlotDigitizer was used for data analysis when the information was shown graphically.22,23 WebPlotDigitizer version 5 is a semi-automatic tool that lets you manually plot two-dimensional charts and extract numerical data. It is free online (https://automeris.io/WebPlotDigitizer/) or as desktop software that may be downloaded.22 This instrument has been employed in several systematic reviews and meta-analyses, encompassing therapy efficacy assessment.24–26 L.Y.M.-L. carried out the data extraction, and M.A.C.-P. Independently checked it. If there were any differences, M.A.C.-F. was consulted and discussed.\n\nResults were entered into a Microsoft Excel (version 2108, Microsoft Corporation, Redmond, WA, USA) spreadsheet and analyzed in the R programming environment (version 4.2.3) using the “metafor” package https://www.metafor-project.org/doku.php/metafor (accessed on 21 February 2024).27 Plotting the synthesis findings and estimating a random-effects model are just a few of the numerous tasks that may be performed by the user with the help of the “metafor” package.27,28 The number of treated participants who tested positive or negative for CD (tpos and tneg, respectively), and the corresponding number of untreated patients (control) who tested positive or negative for CD (cpos and cneg, respectively), were evaluated independently for each therapeutic option available with the “metafor” package”.\n\nA Random Effects Model (RE model) was utilized in the meta-analysis process. According to this model, every study has a unique true effect that varies depending on the differences in participants, interventions, or circumstances between studies.29 The Q value (Q), the I-squared (I2), the tau-squared (T2), and the risk ratio (RR) were also computed. One indicator of heterogeneity among the studies in the meta-analysis is the Q. The sum of the squares representing the discrepancies between the weighted overall effect and the observed effects are used to compute it. A high Q score30 indicates higher levels of study heterogeneity.\n\nThe overall percentage of variance in the estimated effects that results from heterogeneity between studies as opposed to random variation is measured by the I2 statistic. It is represented as a percentage and computed as (Q - df) /Q.31 Excessive I2 values (above 50%) suggest significant variability among the studies.32 In a random effects model, the variation between studies is represented by the T2. Beyond sample error, it evaluates the real dispersion of effects.33 More significant variability between trials that cannot be attributed to chance is indicated by a higher T2 score.34 As the RR of the event happening in the exposed or treated group compared to the unexposed or untreated group, the RR measures the connection between an exposure or treatment and an outcome of interest.35 Compared to the reference group, an exposure or treatment is linked to a higher outcome risk if the relative risk (RR) is more significant than 1. Conversely, a lower risk is suggested when the RR is less than 1. If the relative risk (RR) is 1, then there is no variation in risk among the groups. Confidence intervals are a useful tool for assessing the accuracy of the estimate, in addition to the RR value.36 For all computations, a 99% confidence level was used, with a 0.1 continuity adjustment applied as necessary.\n\n\nResults\n\nIn this work, we performed a systematic review and meta-analysis to evaluate the effectiveness of many treatment options for lowering parasitemia. We considered both established therapies and recently developed, potentially effective medicines for CD. Figure S1 shows a flowchart of the study approach. A search for the MeSH term “Chagas Disease” AND “Treatment Outcome” was performed in the PubMed database and a MeSH term co-occurrence network map was developed. Through the search, 323 scientific publications were published between 1990 and 2023. A network map with 1,020 keywords was produced, with the minimal number of keyword occurrences set at five (Figure 1). Three major clusters were found to have formed during the network map study. Terms including “nitroimidazoles”, “nifurtimox”, “benznidazole”, and “antiprotozoal agents” were found in the cluster about the therapy of CD (highlighted in green). There were other similar denominators, including phrases like “treatment outcome,” “humans,” “Chagas disease,” “female,” “male,” and “Trypanosoma cruzi” (Figure 1).\n\nThe terms found in the first analysis were used to perform a second search in the PubMed database. After the new phrases were associated with “Chagas Disease” and “Treatment Outcome”, the following new search strings were generated: (Chagas Disease [MeSH Terms]) AND (Treatment Outcome [MeSH Terms]) AND (nifurtimox [MeSH Terms]), (Chagas Disease [MeSH Terms]) AND (Treatment Outcome [MeSH Terms]) AND (nitroimidazoles [MeSH Terms]), and (Chagas Disease [MeSH Terms]) AND (Treatment Outcome [MeSH Terms]) AND (Therapeutics [MeSH Terms]) for commonly used treatments (nifurtimox and benznidazole) as well as recently developed treatments against CD.\n\nThere were 40, 107, and 112 studies chosen for the first, second, and third search strings, respectively. We excluded 91, 90, and 66 articles in the identification, screening, and eligibility phases, respectively, based on the three-step selection criteria that we employed. This resulted in the selection of 12 studies for the meta-analysis, one published in 2001, and the others between 2010 and 2014, several of which discussed various treatment choices; as a result, 30 publications in total were included in the investigation. In these investigations, the following novel chemical compounds were examined: Posaconazole, AmBisome®, Cyclopalladated complex 7a, Fexinidazole, Psilostachyin A, Cynaropicrin, Reversible cruzipain inhibitors Cz007 and Cz008, dehydroepiandrosterone-sulfate, VNI, (−)−hinokinin-loaded microparticles, allopurinol, clomipramine, GW788388, and Bis-triazole D0870 (Table 1). The most significant number of studies utilizing animal models to investigate potential novel treatments for CD have been conducted in Brazil. In addition, albeit to a lesser degree, studies on this subject have also been done in several other nations, including Argentina, Canada, France, and the United States (Figure 2).\n\nCD phase\n\nThe acute phase of the disease and its treatment options posaconazole, AmBisome®, Cyclopalladated complex 7a, Fexinidazole, Psilostachyin A, Cynaropicrin, Reversible cruzipain inhibitors Cz007 and Cz008, dehydroepiandrosterone-sulfate, VNI, (−)−hinokinin-loaded microparticles, allopurinol, clomipramine, GW788388, and Bis-triazole D0870 were also covered in twelve studies37–46 that included a total of 741 animals. As Figure 3 shows, the treatment alternatives, particularly Bis-triazole D0870, proved to be effective compared to the control groups. (RR = 8.22, 95% CI [4.80, 14.06]). The tests showed that there was minimal heterogeneity (Q (df = 24) = 14.31, p = 0.94; I2 = 0.0%; T2 = 0.0%)). Two studies37,43 with a total of 138 animals were examined that dealt with the chronic phase of the disease and its treatment choices (VNI, Benznidazole, Nifurtimox, Posaconazole AmBisome®). The treatment alternatives were effective compared to the control groups, especially VNI, as Figure 4 illustrates (RR = 11.29, 95% CI [3.32, 38.36]). There was minimal heterogeneity, according to the tests (Q (df = 4) = 0.33, p = 0.99; I2 = 0.0%; T2 = 0.0%).\n\nSymbol meaning: * Benznidazole, ** Nifurtimox, *** Posaconazole, **** AmBisome®, # Cyclopalladated complex 7ª, ## Fexinidazole, $ Psilostachyin A, $$ Cynaropicrin, & Reversible cruzain inhibitors Cz007, && Reversible cruzain inhibitors Cz008, ¡ Dehydroepiandrosterone sulfate, © VNI, + (−)−hinokinin-loaded microparticles, x Allopurinol, xx Clomipramine, % GW788388, and ^ Bis-triazole D0870. Error bars represent 95% CI. The square shapes represent the estimated RR. The vertical dashed line represents the no-effect line.\n\nSymbol meaning: * Benznidazole, ** Nifurtimox, *** Posaconazole, **** AmBisome®, # Cyclopalladated complex 7ª, ## Fexinidazole, $ Psilostachyin A, $$ Cynaropicrin, & Reversible cruzain inhibitors Cz007, && Reversible cruzain inhibitors Cz008, ¡ Dehydroepiandrosterone sulfate, © VNI, + (−)−hinokinin-loaded microparticles, x Allopurinol, xx Clomipramine, % GW788388, and ^ Bis-triazole D0870. Error bars represent 95% CI. The square shapes represent the estimated RR. The vertical dashed line represents the no-effect line.\n\nExperimental animal models - strains\n\nThe scientific articles were categorized into smaller groups based on the type of animal model that received a T. cruzi inoculation. Only one study42 employed Wistar strain rats. Other mice strains were employed in the other studies: Swiss,37,38,40,41,48 BALB/c,41,44,45 CD-1,46,47 and BALB/cJ.37,39,43 As can be observed in Figure 5, CD−1 was the strain that responded to the treatment the best out of all the investigated strains. Its RR = 11.41, 95% CI [2.05, 63.36], indicates this. The tests showed that there was very little heterogeneity (Q (df = 2) = 1.94, p = 0.38; I2 = 0.0%; T2 = 0.0%)). On the other hand, the strain with the highest number of trials was the Swiss strain, which as shown in Figure 5 with an RR = 8.02, 95% CI [3.49, 18.46]) also showed a substantial response to the various treatment methods (Q (df = 12) = 8.21, p = 0.77; I2 = 0.0%; T2 = 0.0%) showed low heterogenicity. With an RR = 6.58, 95% CI [2.32, 18.69], and negligible heterogenicity (Q (df = 7) = 2.74, p = 0.91; I2 = 0.0%; T2 = 0.0%), BALB/cJ was the strain that responded to the treatment alternatives the least (Figure 4).\n\nSymbol meaning: * Benznidazole, ** Nifurtimox, *** Posaconazole, **** AmBisome®, # Cyclopalladated complex 7ª, ## Fexinidazole, $ Psilostachyin A, $$ Cynaropicrin, & Reversible cruzain inhibitors Cz007, && Reversible cruzain inhibitors Cz008, ¡ Dehydroepiandrosterone sulfate, © VNI, + (−)−hinokinin-loaded microparticles, x Allopurinol, xx Clomipramine, % GW788388, and ^ Bis-triazole D0870. Error bars represent 95% CI. The square shapes represent the estimated RR. The vertical dashed line represents the no-effect line.\n\nExperimental animal models - sex\n\nThe sex of the animal model was used to categorize the scientific studies. RR = 9.36, 95% CI [4.83, 18.12] was the result of 7 studies including female experimental animals37–40,43,44,47; Q (df = 18) = 7.91, p = 0.98; I2 = 0.0%; T2 = 0.0%, indicated a low level of heterogenicity (Figure 5). The studies with the male sex of the experimental animals were 5,41,42,45,46,48 showed a RR = 6.38, 95% CI [2.54, 16.04], with heterogenicity data of Q (df = 10) = 6.62, p = 0.76; I2 = 0.0%; T2 = 0.0% (Figure 5). While analyzing the results, it is clear that female experimental animals are more susceptible than male counterparts to the various CD therapy approaches.\n\nOther research on CD treatments\n\nIn the final analysis of the scientific publications,49 one article about immunotherapy using DNA vaccines in mice was discovered. Immunotherapy boosts the body’s immune response, whereas conventional therapies utilize medications to treat a disease’s symptoms or underlying causes.50 This study was left out of the meta-analysis because of their disparate biological objectives, which make them hard to evaluate in terms of efficacy and safety.\n\n\nDiscussion\n\nMost of the research that made up the meta-analysis was developed between 2010 and 2014. A complex and multidimensional junction of circumstances has impeded development in CD research, leading to an extended time of investigations on new therapeutic drugs. From a scientific standpoint, because of the disease-causing T. cruzi’s inherent genetic variety and capacity to elude the host immune system, its biological complexity has made it extremely difficult to pinpoint effective treatment targets.51–53 Moreover, the formidable challenge facing researchers in conducting extensive clinical investigations and acquiring the necessary resources to drive therapeutic innovation has been exacerbated by inadequate funding for CD-specific research and therapy development.54–56 Compounding this issue is the pharmaceutical industry’s limited interest in the subject, exacerbated by the meager financial prospects of medicines targeting illnesses primarily affecting low-income regions.57,58 The emergence of drug-resistant strains underscores the urgent need for alternative therapeutics, while regulatory hurdles associated with approving novel treatments for neglected diseases further compound the delays in progress.53,59–61 Collectively, these factors converge to create a daunting and intricate landscape that significantly hampers the development of novel CD treatments.\n\nA persistent lack of funding dedicated to Chagas Disease (CD) research and treatment development is a significant obstacle to therapeutic progress.54–56 The lack of financial resources limits researchers’ capacity to conduct robust clinical trials and acquire essential resources. Compounding this issue, the pharmaceutical industry shows limited interest due to the low commercial potential of medications targeting diseases prevalent in low-income regions.57,58 Furthermore, the emergence of drug-resistant strains emphasizes the urgency of finding alternative treatments, yet regulatory hurdles associated with approving novel therapeutics for neglected diseases further contribute to delays.53,59–61 Collectively, these factors create a complex and discouraging landscape that severely hinders the development of new CD treatments.\n\nIn Brazil, researchers conducted three-quarters of the studies that comprise this meta-analysis. This country is a natural hub for study in this field since it is one of the nations most impacted by CD, has a robust research infrastructure, and an epidemiological database.62,63 Research in the nation has also been enhanced by the presence of academic institutions, centers of excellence in tropical health, and financial and research resources.64 On the other hand, even though other Latin American nations are also impacted by CD, scientific research and the health system face structural and financial obstacles that may hinder study.65 Regarding North American countries like the United States of America and Canada, involvement in CD research may depend on the financing available for global health research initiatives and the interests of certain academics or groups.66,67 The lack of urgency in researching and developing therapies may be attributed to the disease’s low incidence in this area.67,68 Only one study from France was considered in the meta-analysis. However, it should be considered that, although non-endemic countries do not directly suffer from CD in their populations, they should consider globalization and human mobility, since these factors increase the possibility of transfer. of diseases to non-endemic countries.69–71 Beyond the moral need to alleviate patients’ suffering, the worldwide scope of CD necessitates a cooperative, international effort to solve the problems this neglected tropical disease presents.\n\nThe results of this study, bis-triazole DO870 and VNI have demonstrated promise as treatments for CD in the acute and chronic stages, respectively. The assessment of these substances’ safety and effectiveness in actual clinical settings is unknown, as no published clinical trials have been performed too far. Similarly, only two of the treatment options included in this meta-analysis—posaconazole and fexinidazole—have undergone clinical trial evaluation. Posaconazole’s clinical research shows that, although exhibiting trypanostatic action during therapy, it was ineffective in treating asymptomatic T. cruzi carriers in the long term. By contrast, it was demonstrated that benznidazole monotherapy outperformed posaconazole, with high RT-PCR conversion rates lasting up to a year. However, in 32% of instances, posaconazole side effects resulted in medication termination.72 The various regimens had an acceptable safety profile in the clinical research evaluating fexinidazole; nonetheless, they were ineffective in treating T. cruzi infection. This has led to discontinuing fexinidazole monotherapy development as a treatment for T. cruzi infection.73 These results highlight the necessity of investigating alternative therapeutic approaches to treat CD as well as the significance of conducting thorough assessments of the safety and effectiveness of medicines in clinical trials.\n\nBoth benznidazole and nifurtimox have been demonstrated to be more successful in lowering parasitemia during the acute phase of CD. These drugs work by preventing the parasite from synthesizing its DNA, which prevents it from multiplying and spreading throughout the host.74 Furthermore, it has been noted that these medications have the ability to cause oxidative damage in the parasite, which helps to eradicate it.75,76 Nevertheless, in the chronic stage of CD, only a limited effectiveness of these treatments has been noted; this could be because of the parasite’s persistence in some body tissues, its difficulty entering those tissues, the host’s weakened immune system, and the disease-related tissue damage.77,78 Consequently, the primary focus of current research is on treating the chronic phase of CD, which is not treated by conventional medications. As was previously indicated, VNI has demonstrated encouraging outcomes for CD’s chronic phase. This compound inhibits the Trypanosomatidae enzyme CYP51,79 which prevents the parasites from synthesizing vital sterols and ultimately compromises the integrity of their cell membranes, killing them.80 It also lessens cardiac fibrosis and inflammation, which may indicate a possibility for stopping or healing heart damage brought on by CD.43 With a wide range of activity against different strains of Trypanosoma infections, including resistant ones, and the potential for improved pharmacokinetics and reduced side effects,81–83 this class of inhibitor may offer safer and more efficient alternatives for treating CD during its chronic stage.\n\nWithin this species, the strains of Trypanosoma cruzi exhibit unique genetic variations. Regarding their genome, virulence, medication resistance, and capacity to elude the host immune system, each of these strains is distinct.84,85 These variations may have an impact on how CD progresses and how affected individuals respond to treatment.86 The main strains of Trypanosoma cruzi studied in the meta-analysis were Tulahuen and Y, for the chronic and acute phases, respectively. The Y strain, recognized for its high virulence, is preferably employed in models attempting to reproduce the acute phase of the disease, allowing the evaluation of therapy efficacy in decreasing parasitemia and initial infection symptoms.87 On the other hand, research examining the long-term pathogenesis and progression of the disease, as well as the evaluation of therapeutic interventions targeted at lowering parasitic burden and preventing or reversing associated organic damage, utilize the Tulahuen strain, which is recognized for its adaptability and ability to induce a stable chronic infection.88,89\n\nConversely, concerning the animal models utilized to assess novel medications against CD, we may bring up the instance of dogs, who serve as significant parasite reservoirs.90 A canine model that accurately mimics human illness has been developed, which makes it easier to assess novel medicinal agents. Routine effectiveness trials are hampered by the high cost and extended lifespan of dogs.91,92 Non-human primates have also been considered possible models, although their usage is restricted due to expense, lack of validation, and ethical concerns.93,94 On the other hand, murine models remain the most popular because of their affordability, portability, and capacity to replicate several facets of human illness.16,95 As demonstrated by the fact that all of the preclinical investigations in this review were carried out in mouse models, they are therefore invaluable resources for researching T. cruzi infection and assessing novel antiparasitic medications.\n\nThe influence on the validity, generalization, and robustness of the results is the intrinsic limitation of the smaller number of scientific publications,96 as is the case in this meta-analysis. A limited data set could not include all available evidence on the topic in question, requiring a cautious interpretation of the results.97 Therefore, it is necessary to support additional research on new treatment options for CD to overcome this deficiency and increase the available scientific evidence. The current meta-analysis enables a thorough assessment of therapy alternatives in a standardized and controlled setting by concentrating on preclinical studies utilizing animal models, laying a strong platform for further research and therapeutic development. Additionally, complex statistical methods, such as those included in the “metafor” package, enable in-depth data analysis, making it easier to control study heterogeneity and accurately estimate treatment effects.98 This helps identify patterns and trends in the effectiveness of treatments, which in turn helps direct decision-making and design of future clinical trials.\n\nTo identify potential compounds and therapeutic targets, extensive research, including drug discovery approaches, is necessary.99 Similar to the studies included in this meta-analysis, potential therapeutic options should be evaluated in preclinical models, such as cell cultures and animal disease models, to determine their efficacy and safety.100 Subsequently, substances that have potential in preclinical research may proceed to clinical trials. There are several important reasons why many therapeutic approaches that show promise in preclinical research are never tested in clinical trials. Initially, moving from preclinical research to clinical trials is an expensive and complex procedure that requires meticulous preparation and substantial monetary means.101 Clinical studies to evaluate potential drugs can often be hampered by a lack of money or investment from the pharmaceutical industry or funding bodies.102,103 Before starting clinical trials, regulatory and safety issues also need to be resolved. Failure to do so could cause further delays or obstacles in transitioning a promising therapy from preclinical to clinical development.104 Additionally, the availability of resources and motivation to conduct clinical trials may be impacted by the lack of interest or priority of the scientific community or the pharmaceutical industry regarding a particular condition, such as CD.105,106\n\n\nConclusions\n\nThis meta-analysis has demonstrated that novel therapeutic options exist that are successful in treating CD; however, most of them are still in the preclinical development stage, and those that have advanced to the clinical trial stage have not demonstrated the best outcomes, meaning that CD treatment remains unresolved. With the primary goal of helping the CD population, the academic community and pharmaceutical companies must collaborate in creating new drugs, as well as continue and apply research that has produced promising results that could hasten the discovery and availability of more effective treatments.\n\nEthical approval and consent were not required.\n\n\nAuthor contributions\n\nConceptualization: M.A.C.-P. and M.A.C.-F.; data curation: M.A.C.-P., L.Y.M.-L., B.M.R.-P., and L.D.G.M.; formal analysis: M.A.C.-P. and M.A.C.-F.; funding acquisition: M.A.C.-P., E.A.F.C., and M.A.C.-F.; investigation: L.D.G.M., H.L.B.C., A.S.G., R.A.M.D., R.C.G., and E.A.F.C.; methodology: M.A.C.-P. and M.A.C.-F.; writing—review and editing: L.D.G.M., H.L.B.C., A.S.G., R.A.M.D., R.C.G., and E.A.F.C. All authors have read and agreed to the published version of the manuscript.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nFigshare: Supplementary figure of results from systematic reviews and meta-analyses (https://doi.org/10.6084/m9.figshare.26240111) 107 and Supplementary tables of results from systematic reviews and meta-analyses (https://doi.org/10.6084/m9.figshare.26312011). 108\n\nThis project contains the following underlying data:\n\n• Figure S1. A flowchart representing the study selection process’s meta-analysis and systematic review.\n\n• Table S1. PRISMA checklist\n\n• Table S2. Data results of systematic review of CD treatment possibilities applied to preclinical research with animal model.\n\n• Table S3. Data results of meta-analysis of CD treatment possibilities applied to preclinical research with animal model.\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 would thanks to CNPq, CAPES (code 001), UFSJ, UFMG, UESC. ASG, RAMA, RCG and EAFC thanks to CNPQ for their PQ/DT Fellowship. The authors also thank to the National Institute of Science and Technology in Industrial Biotechnology (INCT-BI), Brazil.\n\n\nReferences\n\nBonney KM: Chagas disease in the 21st Century: a public health success or an emerging threat? Parasite. 2014 Mar 10; 21(11): 10–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWord Health Organization: Chagas’ Disease (American Trypanosomiasis) Fact Sheet.2023 [cited 2024 Feb 23]. 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}
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[
{
"id": "355966",
"date": "08 Jan 2025",
"name": "Juan Carlos Gabaldon",
"expertise": [
"Reviewer Expertise Parasitology",
"tropical medicine",
"neglected tropical diseases"
],
"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 provide an interesting work comparing a number of different medications and compounds that have been tested in animal models of Chagas disease and carry out a meta-analysis to summarize the results observed. While I congratulate the author team for the effort put in this well-written work, and for highlighting an important issue, such as the limited availability of medications currently available for the treatment of Chagas disease, I feel that the objective and research question that they intend to answer are unclear, and there are some methodological limitations that prevent me from accepting the document in its current state.\nIntroduction: The introduction summarizes the epidemiological landscape of Chagas disease adequately. However, the idea that BNZ and NFX are ineffective in the chronic stage of disease could soon be reconsidered, and I recommend reading the recent meta-analysis by Rassi et al (Ref 3) showing improved clinical outcomes upon parasitic treatment. It is also increasingly accepted that treatment of infected patients should be the norm, unless specific counter-indications exist. The authors could, in turn, mention that existing therapies still fail to clear parasitaemia in a substantial number of patients, and that since sterilizing cure remains the main objective of therapy, interest in the development of new medications remains justified.\nMethods: Authors might want to register the systematic review in the PROSPERO database as well, which includes systematic reviews of human and animal studies. Authors should also include the search strategy used in the different datasets as a supplementary file. A significant body of Chagas disease literature comes from Latin America, as acknowledged in the review by the large number of works from Brazil, and is sometimes described in Spanish and Portuguese. Considering that the author team seems to have both native Spanish and Portuguese speakers, why were non-English articles excluded from the review and meta-analysis? Was blood parasitaemia the only outcome considered by the authors, how was it measured in the different studies, did all of them use PCR, microscopy, was this considered in the inclusion/exclusion criteria? An important advantage of animal studies is that they allow a more comprehensive study of the presence of parasites in tissues, such as the digestive tract, the heart or the CNS. This can be done through biopsies, or non-invasive methods using live luminescence, if parasites expressing a luciferase marker are used. An outcome based on the capacity of drugs to clear parasites from deep organs (rather than only clearing peripheral parasitaemia) should be included, given the intermittent nature of parasitaemia in the chronic stages of T. cruzi infection. Similarly, I disagree with excluding combination therapies. Extensive clinical data shows that the efficacy and safety profile of BNZ and NFX, while far from ideal, has not been beaten by any monotherapy evaluated, which makes it attractive to evaluate the potential role of combined schemes. This could also be included as a sub-analysis comparing combined vs individual treatment schemes. However, my major methodological concerns are related to the fact that the authors do not include any form of risk of bias assessment for any of the studies included in the review, or for the review as a whole. There are currently available tools to evaluate the risk of bias of preclinical studies, I recommend checking the SYRCLE’s risk of bias tool Hooijmans CR et.al., 2014 (Ref 1) , which is consistently used for this purpose. Additionally, there is no assessment of the certainty of the evidence provided by this review, which could be obtained by applying the widely used GRADE criteria, useful for both clinical and preclinical studies. I recommend the authors check reference Romantsik O et.al., 2024 (Ref 2), which provides clear guidelines on how to approach the different segments of a preclinical systematic review. No information on the way potential publication bias was addressed is provided.\nBeyond all of this, I don’t seem to completely understand the objective of the meta-analysis. By comparing animals treated with many different compounds, the research question that the authors seem to be wanting to answer is if anti-parasitic treatment (in general) leads to a higher probability of presenting a negative parasitaemia in animals, which seems to have an obvious answer. If this is not the case, I recommend the authors make the research question more explicit in the methods section.\nIn the statistical analysis section, authors repeatedly refer to “participants” or “patients”, even though the study focuses exclusively on preclinical studies carried out in animals. The term “subjects” or “animals” should be used here, and consistently throughout the text, to avoid confusion.\nI don’t entirely understand the decision to use a random-effects model for the meta-analysis even though the reported heterogeneity in the different comparisons is consistently very low (reported as 0%). The authors should provide further justification for this decision.\nResults: Data extraction sheets of the articles that underwent full-text screening should be provided, along with a table indicating the reason why some of these papers were excluded from the meta-analysis. This could be included as an extra column of the table presented in the supplementary files. The comparison for which the RR is calculated is not clearly described in the text. Based on my interpretation of the figures and text, authors are measuring the RR of presenting a negative parasitaemia (TC-) at the end of the study, which would explain the RRs > 1 being associated with more effective treatment (a higher \"risk\" of showing no parasites in blood). However, this is not disclosed in the text and favors confusion. Similarly, the nomenclature system used by the authors to represent the different compounds tested in each study is very confusing. I recommend including the name of the compound used in each line of the Forest plot to improve readability. Again, the benefit of seeing the aggregated effect of many different treatment schemes seems unclear to me, as it is just showing that some animals who received some anti-parasitic treatments cleared parasitaemia.\nJustification for the decision Systematic reviews of preclinical studies are complex due to the less stringent standardization of methods compared with clinical trials. These reviews often have the objective of prioritizing compounds to move forward for clinical evaluation, and are of value when a large numbers of compounds are being tested in different studies, which does not seem to be the case here. As the authors rightly point out, some compounds whose efficacy was discarded in clinical trials, such as posaconazaole are included in the meta-analysis, while others that show promise to progress to clinical stages, such as benzoxaboroles and cyanotriazoles are not, casting doubts on the applicability of the results.\nI applaud the authors interest in bringing attention to the limited availability of new therapeutic alternatives for Chagas disease, and invite them to keep working on the subject. However, If the authors just want to provide a high-level image of the compounds currently being evaluated in preclinical stages, perhaps a well-structured scoping literature review is a better format to do so, as would also allow them to describe the benefits and pitfalls of more drugs currently under study.\nIf the authors feel that a systematic review of preclinical studies is necessary, or the best way to present their work, then I encourage them to design a concise research question they want to answer, and guarantee that issues such as the risk of bias assessment and the certainty of evidence of the work are adequately addressed, as these are essential for the interpretation of the results.\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? 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.) No",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-885
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https://f1000research.com/articles/12-606/v1
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06 Jun 23
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{
"type": "Research Article",
"title": "Proteomics analysis of carcinogenesis in a rat model of mammary cancer induced by DMBA (7,12-dimethylbenz[a]anthracene)",
"authors": [
"Dyah Ayu Oktavianie Ardhiana Pratama",
"Anggun Nur Cahyati",
"Ulayatul Kustiati",
"Andreas Bandang Hardian",
"Fajar Shodiq Permata",
"Anggun Nur Cahyati",
"Ulayatul Kustiati",
"Andreas Bandang Hardian",
"Fajar Shodiq Permata"
],
"abstract": "Background: Mammary cancer, called breast cancer in humans, results from the abnormal growth of cells in the mammary glands that attack the surrounding tissue. The process of carcinogenesis at the molecular level can be monitored through the production of proteins as biomarkers for carcinogenesis. 7,12-Dimethylbenz[a]anthracene (DMBA) is a known carcinogenic compound. This study aimed to analyze the proteomic profile as critical data regarding DMBA-induced carcinogenesis in Sprague‒Dawley rats. Methods: Experimental animals were divided into two groups: a treatment group given DMBA at a dose of 10 mg/kg (intramammary) at intervals of 48 hours for a total of 10 doses, and a negative control group that was not given any treatment. Measurement of the total protein concentration was carried out using a spectrophotometer, and the data were analyzed using a t-test, while the characterization of protein profiles was carried out based on molecular weight data using SDS‒PAGE. Mammary gland histopathology was evaluated by hematoxylin and eosin (H&E) staining. Results: The results showed a significant (p<0.05) increase of 27% in the total protein concentration in the rat mammary cancer model. The results of proteomic characterization showed a protein profile containing proteins of 187, 169, 68, 64, 53, 41, 24, 18, and 14 kDa, which were suspected to be HER-2, Nischarin, COX-2, Albumine, Vimentin, ACTB, TNF, p16, and fatty acid binding protein 3 (FABP3), respectively. Histopathology of the mammary glands showed an irregular and indistinct arrangement of the alveoli and extensive epithelial cell proliferation from the surface to the lumen of the mammary ducts, and the mammary stroma showed the formation of new epithelial cells, which were cancer cells that spread to surrounding tissue. Conclusions: The proteomic profile was strongly associated with morphological alterations in mammary carcinogenesis in a rat model of DMBA-induced mammary cancer.",
"keywords": [
"Mammary cancer",
"DMBA",
"proteomic",
"protein profile",
"histopathology alteration"
],
"content": "Introduction\n\nMammary cancer, called breast cancer in humans, results from the uncontrolled growth of cells in the mammary glands, the glandular ducts extending from the lobule to the nipple, and the surrounding connective tissue. Mammary cancer can spread outside the mammary gland through blood vessels and lymph vessels.1 The incidence of mammary cancer is high in animals, with incidence rates of between 41 and 53% in female dogs and approximately 86% in female cats.2 The uncontrolled spread of cancer cells, or metastasis, can lead to death.3 According to global cancer data, breast cancer is the most commonly diagnosed cancer and the fifth leading cause of death in women.4 7,12-Dimethylbenz[a]anthracene (DMBA) is a carcinogenic substance with cytotoxic, mutagenic, immunosuppressive, and carcinogenic properties.5 DNA mutations were previously analyzed in vitro and in vivo in DMBA-induced mice. This analysis showed that 99% of DNA is depurinated by one-electron oxidation and that the 12-methyl of DMBA binds to the N-7 of adenine or guanine at an adenine:guanine ratio of 1:4. This binding forms a carcinogen-DNA adduct that affects DNA replication, thereby affecting the expression of the encoded protein.6\n\nDNA damage caused by carcinogens leads to uncontrolled gene mutations that result in protein changes and dysregulated cell proliferation, triggering the overgrowth of cancer cells.7 Proteins are functional components of cells that regulate all cellular activities. Therefore, changes in protein expression in human breast cancer tissue play an important role in carcinogenesis. Malignant transformation at the molecular level can be detected through the excessive production of proteins encoded by oncogenes, namely, genes that stimulate cell growth and differentiation. Breast cancer refers to a group of neoplastic diseases with high intratumoral and intertumoral heterogeneity. Proteomic characterization of breast cancer has been used to understand molecular abnormalities, especially based on the signature of cancer-associated proteins (CAPs), a distinct group of potential cancer-associated biomarkers. Downregulation or upregulation of protein expression may contribute to the dysregulation of cellular functions, leading to tumor development and effects on patient survival.8 For example, TNF-α, after binding to TNFR1 on the plasma membrane, activates NF-κB to promote the survival of tumor cells. Poor patient survival is associated with higher expression of TNF-α because TNF-α is a proinflammatory cytokine whose expression increases during tumor progression.9 Overexpression of HER-2 in breast cancer can regulate antiapoptotic signals.8\n\nBased on this background, this study aimed to characterize the proteomic profile associated with histopathological changes in mammary cancer and can be considered a preliminary study identifying the molecular weights of the proteins expressed in mammary cancer tissue. In addition, the difference between the protein concentration in mammary cancer tissue and that in normal tissue was determined.\n\n\nMethods\n\nThis study used rats as experimental animals obtained from and treated at Universitas Brawijaya. Rats were housed and maintained in a temperature-controlled room with a temperature of 21°C, a relative humidity of 45–65% and a 12 h/12 h light/dark cycle, with one week of acclimatization. Rats were provided food and water ad libitum during the treatment. Researchers and laboratory staff conducted observations twice a day. The experimental animals selected were 18 female Sprague–Dawley rats (Rattus norvegicus), 10 weeks old, weighing 150–170 gr. The sample size was calculated using Federer’s formula:\n\nT = number of groups\n\nN = number of samples.\n\nThis study was performed in accordance with the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines.34 All treatments were carried out using the Three Rs principle based on the ARRIVE guidelines. The research was conducted in the laboratory of experimental animals, Faculty of Veterinary Medicine and Biosciences Laboratory, Universitas Brawijaya. Experimental animals were grouped into the control and treatment groups in a completely randomized design (CRD). GraphPad Prism (RRID:SCR_002798) version 8.0 was used to generate the CRD so that all samples received the same treatment. In this study, the number of necessary experimental animals was calculated using Federer’s formula to reduce the number of animals used. In this study, we only used healthy animals, both physically and physiologically, so animals that did not meet this requirement were excluded from the experiment.\n\nWe followed the standard ethical guidelines for animal care and use in this study. Moreover, all of the experimental protocols were approved by the Research Ethics Committee of the Universitas Brawijaya, Indonesia (Ethical Clearance No. 079-KEP-UB, approved on July 8th, 2021). The natural habits of the animals were considered, and we placed the animals under appropriate conditions as described above so that any harm, including pain and distress, to those animals was minimized.\n\nIn this study, researchers and laboratory staff were blinded to the identification numbers of the rats before their assignment to the control or treatment group in this study and remained blinded to those numbers throughout the study. The distribution of animals into the control and treatment groups was carried out using a CRD by laboratory staff who did not otherwise participate in this study to ensure there was no trend in group assignment and to prevent false-positive results.\n\nDMBA was dissolved in corn oil and normal saline (NS) at a DMBA:corn oil/NS ratio of 3:1. Tumorigenesis was induced in each rat in the treatment group by intramammary injection of DMBA at a dose of 10 mg/kg body weight (BW) in a 1 ml volume per rat, with 0.5 ml injected into the right and 0.5 ml injected into the left flank. Ten rounds of induction were conducted at 48-hour intervals. The tumors in rats in the treatment group were palpated 1-2 times a week after DMBA injection. The size of visible tumors did not exceed 40 mm, and the formation of only one tumor was induced, based on the guidelines of the Institutional Animal Care and Use Committee (IACUC). The rats in the control group did not receive any injection into the mammary glands. All rats were sacrificed by cervical dislocation, and the nodule that had formed was then excised from each rat in the treatment group, while the mammary gland was excised from each rat in the negative control group. The samples obtained were subjected to hematoxylin and eosin staining to describe the mammary gland structure, and proteomic profiling was carried out using SDS–PAGE. This study directly compared protein profiles and mammary gland tissues between normal rats and rats induced with DMBA.\n\nFormalin-fixed samples were gradually dehydrated in increasing ethanol concentrations and then cleared in xylene. Then, samples were embedded in paraffin and cut into five-micrometer sections using a rotary microtome. A standard hematoxylin and eosin (H&E) procedure was used to stain the sections, and images of the slides were acquired under a light microscope.\n\nAll samples were ground to homogeneity using a mortar. Then, 1.5 ml of PBST-PMSF was added to the extract. The suspension was sonicated for 20 minutes and then centrifuged at 6,000 rpm and 25°C for 15 minutes. The supernatant was transferred into a new 500 μl microtube, homogenized by adding absolute ethanol at an ethanol:suspension ratio of 1:1, and stored overnight in the freezer. Next, the sample was centrifuged at 10,000 rpm and 4°C for 15 minutes. The absolute ethanol was discarded, and the extract was air-dried until the odor of ethanol was no longer detectable and was then homogenized by adding 100 μl of Tris-HCl (pH 6.8). The extracts were stored at -20°C.\n\nProtein extraction was followed by NanoDrop spectrophotometry to measure the concentration and purity of the proteins in the sample. The NanoDrop instrument determines the protein concentration by measuring the absorbance of the sample at 280 nm. Protein concentrations were quantified by comparing the protein concentrations in the control and treatment groups as percentages.\n\nSDS–PAGE was conducted according to the Mini-PROTEAN® Tetra Cell (Bio-Rad Laboratories Inc. #cat number 1658005, Berkeley, California) instruction manual. The concentrations of the extracted total protein samples were equalized to the lowest concentration in any sample, i.e., 21.14 mg/ml, and proteins were then denatured by the addition of Reducing Sample Buffer (SDS, Tris-HCl (pH 6.8), 100% glycerol, mercaptoethanol, and bromophenol blue) at a 1:1 ratio. The samples were then heated at 95°C for 5 minutes. A 12.5% resolving gel and a 3% stacking gel were used. The gel was mounted on the clamping frame and the frame was lowered into the mini tank; then, running buffer was added to the inner compartment of the clamping frame until the compartment was full. Samples that had been heated with RSB were then loaded into each well at a volume of 20 μl, and one well was filled with protein marker. Electrophoresis was performed at 100 V until the tracking dye reached a level of 0.5 cm above the bottom of the resolving gel. The staining process began with the removal of the gel from the plate, and the gel was then placed in a container containing Coomassie blue stain. The gel was incubated with shaking for 10 minutes so that the dye was evenly distributed, and color removal of the remaining dye was performed by overnight incubation with a mixture of methanol, glacial acetic acid, and H2O in a shaker.\n\nThe concentrations determined for the control and treatment groups were analyzed with IBM SPSS Statistics (RRID:SCR_016479) version 26 using the Shapiro–Wilk normality test and Levene’s test for homogeneity with a significance level of 0.05 (α = 0.05). Then, an independent samples t-test was conducted to analyze the difference in concentration between the groups. Two tests were performed with two replicates each. We visualized the bands on the SDS–PAGE gels and predicted the name of the protein corresponding to each band based on calculation of its molecular weight.\n\n\nResults\n\nThe results of analysis of the average total protein concentrations in the two groups using an independent samples t-test are presented in Table 1.33\n\nSignificance analysis using the independent samples t-test showed a Sig (2-tailed) value of 0.006. These results indicated that the two groups had significantly different mean protein concentrations (p < 0.05). The total protein concentration in the treatment group was increased by 27% compared to that in the negative control group.\n\nThe visualization of the protein profile in rat mammary gland tissue samples determined using 12.5% SDS–PAGE is presented in Figure 1. The observable protein bands on the SDS–PAGE gel can describe the state of the carcinogenic process in the rat mammary gland. In addition to the appearance of a protein band, the thickness of the protein band indicates the concentration of the protein. The classification of proteins expressed in rat mammary gland tissue, as determined by electrophoresis, is shown in Table 2.\n\nA. Control group. By gel electrophoresis, seven bands at 14, 18, 30, 41, 53, 64, and 269 kDa were observed in the control group. B. Nine bands at 14, 18, 24, 42, 53, 64, 68, 169, and 186 kDa were observed in the treatment group. Between the control and treatment groups, we observed three different bands. The proteins are described in Table 2. The molecular weights of the proteins in the molecular marker are shown in red, and the molecular weights of proteins in the samples are shown in black.\n\nDMBA, 7,12-dimethylbenz [a]anthracene; FABP3, fatty acid binding protein 3.\n\nThe development of DMBA-induced tumors in the mammary glands of rats in the mammary cancer model was observed through H&E staining. The histology of the mammary glands under normal conditions (control group) in this study showed that the alveoli exhibited a rounded structure with a surface lined with epithelial cells, myoepithelial cells, and basal membranes. The mammary ducts were empty and lined with cuboidal epithelial cells. The stroma comprises connective and fat tissue (Figure 2). Histopathological examination of the mammary glands of rats in the model of DMBA-induced mammary cancer (treatment group) showed an irregular and indistinct arrangement of the alveoli. The epithelial cells were not cuboidal and contained hyperchromatic nuclei. The mammary ducts were filled with proliferating epithelial cells from the surface of the ducts to the lumen of the ducts. The mammary stroma showed the formation of new epithelial cells that were cancer cells and spread to surrounding tissues (Figure 3).\n\nA. Control group. B. Treatment group. The mammary stroma showed the formation of new epithelial cells that were cancer cells and spread to surrounding tissues and hyperplasia with mitotic fibrocytes in the dermis. (a) alveoli; (d) ducts; (s) stroma. Scale bar, 100 μm. DMBA, 7,12-dimethylbenz [a]anthracene.\n\nA. Control group. The alveoli contain irregular and cuboid cells with no hyperchromatic nuclei. B. Treatment group. The alveoli in the treatment group showed an irregular and indistinct arrangement. The epithelial cells were not cuboidal and contained hyperchromatic nuclei. The mammary ducts were filled with proliferating epithelial cells from the surface of the ducts to the lumen of the ducts. (a) alveoli; (d) ducts; (s) stroma; (m) malignant cells (the cells appeared larger); (n) nuclei (hyperchromatic with a large size). Scale bar, 100 μm. DMBA, 7,12-dimethylbenz[a]anthracene.\n\n\nDiscussion\n\nIn the present study, mammary cancer development in DMBA-induced rats was confirmed by proteomic analysis and histopathological examination of the mammary glands of rats. The total protein concentration in the DMBA-treated rats was increased by 27% compared to that in the control group. This finding is also consistent with a previous study, in which the total Albumine and globulin concentration in a group of female patients with breast cancer had an average value of 7.63 ± 0.14 g/dl and was higher than those in the control group and in the group of healthy women, in which the mean value was 6.14 ± 1.84 g/dl.10 In this study, the difference between the protein concentration in the control group and the DMBA-treated group of rats was thought to be related to proto-oncogenes that play a role in promoting and increasing cell growth and division, which can become activated if there is an alteration or mutation. The increased appearance of oncoprotein bands is a characteristic related to excessive oncoprotein expression in cells. There is an increase in the production of mRNA transcripts of oncogenes and in the number of copies of oncogenes.11 The carcinogenesis process at the molecular level can be detected by the excessive production of oncoproteins. Activation of oncogenes stimulates faulty production of growth factor receptors, indicating continued growth in the absence of external stimuli. Uncontrolled cell division without cell maturation causes impaired cell differentiation.12 At a later stage, impaired cell differentiation causes malignant transformation of cells. In this study, exposure to DMBA as a carcinogenic agent caused changes in the nucleotide sequence of proto-oncogene DNA, resulting in changes in gene expression.13\n\nProteomic profiling was performed using SDS–PAGE to visualize changes in gene expression in DMBA-treated rats. The observable protein profile can describe the state of carcinogenesis in rat mammary gland tissue. In addition to the appearance of a protein band, the thickness of the protein band indicates the protein concentration. According to the results of this study, a protein with a molecular weight of 187 kDa was expressed in the DMBA-treated group but not in the control group. This protein is suspected to be the HER-2 protein, which has a molecular weight of 185 kDa (https://www.uniprot.org/uniprotkb/Q003I6/entry).14 HER-2 is a proto-oncogene that controls the growth and development of mammary epithelial cells. In mammary carcinomas in rats, there is amplification of this gene such that the cell division rate is doubled and cell growth increases.15 DNA damage due to DMBA exposure results in a single-amino acid mutation by substituting a valine residue in the transmembrane domain with glutamic acid.16 This substitution induces dimerization of the HER-2 oncoprotein in the cell membrane, with results similar to the induction of activation by growth factors so that activation continues even in the absence of external growth stimuli.17 Overexpression of the HER-2 gene occurs in approximately 15–30% of breast cancers and correlates with cell proliferation.18 This finding relates to the histopathological appearance shown in Figure 1B, which was characterized by cell proliferation in the alveoli and from the surface to the lumen of the mammary ducts.\n\nA protein band with a molecular weight of 169 kDa was visible in all tissues, in both the negative control and DMBA-treated groups, and there was no difference in the protein band thickness between the two groups. The corresponding protein was considered to be Nischarin, with a molecular weight of 166 kDa (https://www.uniprot.org/uniprotkb/A0A8I5ZTG9/entry). Nischarin is an integrin-binding protein known to be a novel tumor suppressor and to play a critical role in mammary cancer cell migration and invasion in rats.19 Research conducted by Chang et al.20 showed that increased Nischarin expression in tumor cells reduces the invasive and migratory abilities of cancer cells. Analysis of a total of 962 patients with breast cancer revealed that 0.3% of invasive carcinomas showed loss of Nischarin expression and that 0.7% of invasive carcinomas expressed mutated Nischarin.21\n\nA protein band with a molecular weight of 68 kDa was observed in all mammary gland samples of DMBA-treated rats and was not observed in samples from negative control rats. The corresponding protein was suspected to be the COX-2 protein, with a molecular weight of 69 kDa (https://www.uniprot.org/uniprotkb/Q8CIP1/entry). COX-2 plays a role in the conversion of arachidonic acid to prostaglandins. COX-2 induces angiogenesis through three products, thromboxane A2, prostacyclin, and prostaglandin E2, which stimulate vascular endothelial growth factor (VEGF) production in angiogenesis. COX-2 upregulation is observed in 40% of patients with invasive breast carcinoma and correlates with poor prognosis. COX-2 upregulation promotes tumor formation and progression to metastasis, in addition to increases in angiogenesis, cell migration, and invasion.22 This finding can be related to the histopathological image shown in Figure 3B, which shows the formation of new epithelial cells in the mammary stroma that were cancer cells spreading to the surrounding tissues.\n\nA protein band with a molecular weight of 64 kDa was observed in all mammary cancer tissues and all normal tissues, but there was a difference in the appearance of the bands formed. The band visualized in the negative control sample was thicker than the band visualized in the treatment group sample. This indicates a reduction in the concentration of the protein in the treatment group sample. The corresponding protein was thought to be Albumine, with a molecular weight of 65 kDa (https://www.uniprot.org/uniprotkb/A0A0G2JSH5/entry). Cancer and lack of nutrition are among the causes of a decreased Albumine level. Cancer cells proliferate over an indefinite period of time, and the number continues to increase. Under these conditions, cancer cells and normal cells compete for nutrients. Cancer cells require all available nutrients, resulting in the death of normal cells due to a lack of nutrients.\n\nA protein band with a molecular weight of 53 kDa was observed in all negative and DMBA-treated samples. There was a thickening of the band in all treatment group samples. The corresponding protein was suspected to be Vimentin, which has a molecular weight of 53 kDa (https://www.uniprot.org/uniprotkb/P31000/entry). Vimentin is a protein that forms intermediate filaments, which are components of the cytoskeleton, and is expressed in cells that are embryonically derived from the mesenchyme and in epithelial cells.23 Vimentin is used as a marker of mesenchymal cells or cells undergoing epithelial-to-mesenchymal transition (EMT) during normal and metastatic development.24\n\nIn both groups, a 41 kDa protein band was visible, but in the DMBA-treated group, the band was thickened. This protein was predicted to be actin (ACTB), which has a molecular weight of 41 kDa (https://www.uniprot.org/uniprotkb/Q9JLX9/entry). ACTB plays important roles in cell migration and division. Analysis of ACTB expression based on The Cancer Genome Atlas (TCGA) database showed abnormal expression of ACTB in breast cancer cases with mutation or amplification of ACTB. That study also showed that ACTB expression in invasive breast carcinoma tissue was higher than that in normal tissue and that there was a relationship between high ACTB expression and poor prognosis in breast cancer.25\n\nNegative control samples showed a protein band with a molecular weight of 30 kDa that was not observed in DBMA-treated samples. The corresponding protein was thought to be prohibitin, which weighs 29 kDa (https://www.uniprot.org/uniprotkb/Q5XIH7/entry). Prohibitin can inhibit cell proliferation by inducing blockade of the S/G2 transition and promoting apoptosis.26 A study conducted by Najm et al.27 in cancers showed a missense mutation located in the sequence of the prohibitin gene encoding the Rb-binding domain, causing the production of abnormal protein products and loss of activity.\n\nThe protein band with a molecular weight of 24 kDa was observed only in the DMBA-treated group. The corresponding protein was predicted to be TNF-α, with a molecular weight of 25 kDa (https://www.uniprot.org/uniprotkb/P16599/entry). In a mammary cancer model, rats with mammary cancer showed greater proinflammatory cytokine secretion than normal rats. This is thought to be due to an enhanced immune response associated with increased immune cell activity due to the presence of antigens. Cancer cells express antigens in the form of mutated genes or overexpressed normal proteins. These antigens are recognized by the immune system to elicit an immune response.28\n\nThe protein band showing a molecular weight of 18 kDa was observed in all treatment group samples except for K3 and K4. This protein was considered to be p16 in the INK4 family, with a molecular weight of 17 kDa (https://www.uniprot.org/uniprotkb/Q9R0Z3/entry). The INK family is a family of cyclin-dependent kinase inhibitors that can inhibit Cdk activity by forming a stable complex with Cdk proteins, thereby preventing Cdk proteins from binding to cyclin D during the cell cycle. Deregulation of the cell cycle is a crucial feature of carcinogenesis. P16 is one of the proteins involved in the cell cycle. The expression of p16 in cancer can constitutively inactivate the tumor suppressor retinoblastoma (Rb). The change in p16 expression leads to gene downregulation and promotes the formation of epithelial cancers.29 In this study, seven treatment group samples expressed the p16 protein, while the other two did not, a phenomenon thought to indicate the heterogeneity of this type of cancer. An association with p16 overexpression was found for breast cancer, and p16 expression was found to be a prognostic indicator in breast cancer.29 In both of these cases, the luminal A subtype showed lower p16 expression than the other subtypes. In contrast, the triple-negative subtype showed higher p16 expression than the other subtypes. Some cancers occur due to the complete loss or malfunction of tumor suppressor genes. According to Musyarifah et al.,30 positive p16 expression is more likely to be present in cancers with higher stages and higher histopathological degrees.\n\nRegarding the protein band showing a molecular weight of 14 kDa, observed in the negative and treatment groups, the corresponding protein was suspected to be fatty acid binding protein 3 (FABP3), with a molecular weight of 14 kDa (https://www.uniprot.org/uniprotkb/A0A8I6A2E9/entry). FABP3 plays roles in fatty acid transport, cell growth, and gene transcription. In cancer, this protein acts as a tumor suppressor.31 Reduced FABP3 expression in breast cancer cells was confirmed to occur by hypermethylation of the FABP3 promoter.32 Hypermethylation is an increase in methylation in DNA that should not be methylated. Inhibition of transcription due to DNA methylation in the promoter prevents the gene from being expressed. Research on the molecular characteristics of mammary cancer as markers of cancer incidence has provided new information regarding the molecular heterogeneity of tumors. Molecular characterization has revolutionized mammary cancer research and the choice of therapy. Because mammary cancer in animals or breast cancer in humans is a disease with a high mortality rate, consideration of molecular profiling is anticipated to be very important in the selection of treatment options and development of new drugs.\n\n\nConclusions\n\nThe total protein concentration in the mammary tissues of rats with DMBA-induced mammary cancer was significantly increased by 27%. The proteins determined by SDS–PAGE to be expressed in mammary tissues in the rat model of DMBA-induced mammary cancer were thought to be HER-2, Nischarin, COX-2, Albumine, Vimentin, Actin, TNF-α, p16, and FABP3. DMBA induction can activate the expression of mammary cancer marker proteins, such as HER-2 and COX-2, and reduce the expression of the prohibitin protein, which plays a role in mammary carcinogenesis. The protein profile of mammary tissue was associated with its histopathological appearance, which showed an irregular and indistinct arrangement of the alveoli, proliferation of mammary duct epithelial cells, and the formation of new epithelial cells in the mammary stroma. In this study, we found that proteins with altered expression in cancer can be markers of tumorigenesis, diagnostic and prognostic markers, and therapeutic targets. This study discusses protein expression in an animal model of DMBA-induced mammary cancer. We found several potential protein biomarkers related to breast cancer development pathways. We hope these findings will encourage further clinical validation studies and provide insights and directions for future research.\n\n\nData availability\n\nZenodo: The Role of Proteomics Analysis in Carcinogenesis in a Rat Mammary Cancer Model Induced by DMBA (7,12-dimethylbenz(α)anthracene). https://doi.org/10.5281/zenodo.7796773.33\n\nThis project contains the following underlying data:\n\n- Protein Molecular Weight.xlsx\n\n- Protein Nanodrop Spectrophotometer.xlsx\n\nZenodo: ARRIVE checklist for ‘The role of proteomics analysis in carcinogenesis in a rat mammary cancer model induced by DMBA (7,12-Dimethylbenz[a]anthracene)’. https://doi.org/10.5281/zenodo.7839767.34\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgments\n\nThe authors would like to thank the Faculty of Veterinary Medicine, Universitas Brawijaya, for awarding the research grant. The authors also thank the Laboratory of Veterinary Pathology and the Animal Disease Diagnostic (ADD) Laboratory, Faculty of Veterinary Medicine, Universitas Brawijaya, for facilitating this research project.\n\n\nReferences\n\nFernandez-Martinez A, Krop IE, Hillman DW, et al.: Survival, pathologic response, and genomics in CALGB 40601 (Alliance), a neoadjuvant Phase III trial of paclitaxel-trastuzumab with or without lapatinib in HER2-positive breast cancer. J. Clin. Oncol. 2020; 38(35): 4184–4193. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBadowska-Kozakiewicz AM, Ferguson NL, Bell J, et al.: Prevalence and Etiology of the Most Common Malignant Tumours in Dogs and Cats. Bulg. J. Vet. Med. 2006; 9(2): 85–98.\n\nDobson JM: Breed-Predispositions to Cancer in Pedigree Dogs. ISRN Vet. Sci. 2013; 2013: 1–23. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeng F, Liao M, Qin R, et al.: Regulated cell death (RCD) in cancer: key pathways and targeted therapies. Signal Transduct. Target. Ther. 2022; 7(1): 286. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAl-Muhtaseb SI: Serum and saliva protein levels in females with breast cancer. Oncol. Lett. 2014; 8(6): 2752–2756. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAhmadi SE, Rahimi S, Zarandi B, et al.: MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies. J. Hematol. Oncol. 2021; Vol. 14(1): 121. BioMed Central. PubMed Abstract | Publisher Full Text | ,Free Full Text\n\nHanahan D: Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022; 12(1): 31–46. PubMed Abstract | Publisher Full Text\n\nTomesz A, Szabo L, Molnar R, et al.: Effect of 7,12-Dimethylbenz (α) anthracene on the Expression of miR-330, miR-29a, miR-9-1, miR-9-3 and the mTORC1 Gene in CBA/Ca Mice. In Vivo. 2020; 34(5): 2337–2343. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMatić S, Quaglino E, Arata L, et al.: The rat ErbB2 tyrosine kinase receptor produced in plants is immunogenic in mice and confers protective immunity against ErbB2+ mammary cancer. Plant Biotechnol. J. 2016; 14(1): 153–159. PubMed Abstract | Publisher Full Text\n\nFeng Y, Spezia M, Huang S, et al.: Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis. 2018; 5(2): 77–106. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHamza AA, Khasawneh MA, Elwy HM, et al.: Salvadora persica attenuates DMBA-induced mammary cancer through downregulation oxidative stress, estrogen receptor expression and proliferation and augmenting apoptosis. Biomed. Pharmacother. 2022; 147: 112666. PubMed Abstract | Publisher Full Text\n\nZhang Y, Zhang Q, Cao Z, et al.: HOXD3 Plays a Critical Role in Breast Cancer Stemness and Drug Resistance. Cell. Physiol. Biochem. 2018; 46(4): 1737–1747. PubMed Abstract | Publisher Full Text\n\nIqbal N, Iqbal N: Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol. Biol. Int. 2014; 2014: 1–9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCai YJ, Ma B, Wang ML, et al.: Impact of Nischarin on EMT regulators in breast cancer cell lines. Oncol. Lett. 2020; 20(6): 1–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChang C, Wei W, Han D, et al.: Expression of Nischarin negatively correlates with estrogen receptor and alters apoptosis, migration and invasion in human breast cancer. Biochem. Biophys. Res. Commun. 2017; 484(3): 536–542. PubMed Abstract | Publisher Full Text\n\nMaziveyi M, Alahari SK: Breast cancer tumor suppressors: A special emphasis on novel protein nischarin. Cancer Res. 2015; 75(20): 4252–4259. PubMed Abstract | Publisher Full Text\n\nEsbona K, Inman D, Saha S, et al.: COX-2 modulates mammary tumor progression in response to collagen density. Breast Cancer Res. 2016; 18(1): 15–35. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPandita V, Ajila V, Babu GS, et al.: Vimentin and its role as a biomarker in health and disease. Gulhane Med. J. 2021; 63(4): 232–237. Publisher Full Text\n\nRamos I, Stamatakis K, Oeste CL, et al.: Vimentin as a multifaceted player and potential therapeutic target in viral infections. Int. J. Mol. Sci. 2020; 21(13): 1–27. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGu Y, Tang S, Wang Z, et al.: A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers. Bioengineered. 2021; 12(1): 6166–6185. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu P, Xu Y, Zhang W, et al.: Prohibitin promotes androgen receptor activation in ER-positive breast cancer. Cell Cycle. 2017; 16(8): 776–784. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNajm M, Sadaf A, Akhtar N, et al.: Prohibitin gene regulation in cancer and its possible therapeutic potential. J. Curr. Oncol. 2021; 4(1): 35. Publisher Full Text\n\nCriscitiello C: Tumor-associated antigens in breast cancer. Breast Care. 2012; 7(4): 262–266. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSalih MM, Higgo AA, Eed EM: Prognostic Significance of p16 Protein Expression in Breast Cancer. In Vivo. 2022; 36(1): 336–340. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMusyarifah Z, Agus S, Yenita Y, et al.: Hubungan Ekspresi Protein 16 (p16) dengan Derajat Histopatologik dan Invasi Perineural pada Karsinoma Sel Skuamosa Kepala dan Leher. Jurnal Kesehatan Andalas. 2020; 9(3): 282. Publisher Full Text\n\nTang Z, Shen Q, Xie H, et al.: Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC). Oncotarget. 2016; 7(29): 46253–46262. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLopes-Coelho F, André S, Félix A, et al.: Breast cancer metabolic cross-talk: Fibroblasts are hubs and breast cancer cells are gatherers of lipids. Mol. Cell. Endocrinol. 2018; 462: 93–106. PubMed Abstract | Publisher Full Text\n\nPratama DA, Cahyati AN, Permata FS, et al.: The Role of Proteomics Analysis in Carcinogenesis in a Rat Mammary Cancer Model Induced by DMBA (7,12-dimethylbenz(α)anthracene). [Dataset]. Zenodo. 2023. Publisher Full Text\n\nPratama DA, Cahyati AN, Permata FS, et al.: ARRIVE checklist for ‘The role of proteomics analysis in carcinogenesis in a rat mammary cancer model induced by DMBA (7,12-Dimethylbenz [a]anthracene)’. [Dataset]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "181612",
"date": "26 Jul 2024",
"name": "Muhammad Luqman Nordin",
"expertise": [
"Reviewer Expertise veterinary oncology",
"pharmacology",
"toxicology and pharmaceutics ( vaccine and drugs delivery technology)."
],
"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\nOverall, this article is good and contributes to the novelty and very valuable knowledge especially with regards to mammary carcinoma in animals. As the prevalence of cancer is increasing among animals, this study provides a high level of academic and scientific writing.\nMinor comment: it would be better if you can provide a picture of mammary cancer development on rats. The mammary cancer results from the uncontrolled growth of cells in the mammary glands, the glandular ducts extending from the lobule to the nipple, and the surrounding connective tissue. Normally, there will be masses present at the nipple/mammary area.\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": "12094",
"date": "05 Aug 2024",
"name": "Dyah Ayu Pratama",
"role": "Author Response",
"response": "Dear Reviewer, Thank you very much for your positive comments and suggestions. Related with your suggestion to provide a description of mammary cancer development on rats, I have supplemented with an explanation of the development of mammary cancer in rats as a result of DMBA induction."
}
]
},
{
"id": "181616",
"date": "26 Jul 2024",
"name": "Hevi Wihadmadyatami",
"expertise": [
"Reviewer Expertise Cell biology",
"cancer mechanism",
"neurodegeneration",
"histology"
],
"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: Please make a stronger background on the importance of the detection of the cancer biomarker or proteomics analysis on the rat model.\nMaterial and method: Please complete all the data of the reagent which is used on the experiment.\nResults: Please provide a more clean version on the part of molecular weight of figure 1, so the reader can read clearly the molecular weight of each protein which is expressed on the mammary tissue gland.\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": "12095",
"date": "05 Aug 2024",
"name": "Dyah Ayu Pratama",
"role": "Author Response",
"response": "Dear Reviewer, I appreciate and am thankful for your positive comments and suggestions. As your suggestion on introduction section, I have highlight the importance of this research especially related with proteomic analysis of cancer biomarkers on cancer detection and prediction, as well in the development of cancer therapy. I have also complete the data of reagent which is used in this research."
}
]
},
{
"id": "305378",
"date": "05 Aug 2024",
"name": "Jasni Bin Sabri",
"expertise": [
"Reviewer Expertise Pathology: Pathogenesis",
"Histopathology and Ultrastructural Pathology."
],
"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 a very good study and has present and future worldwide applications for cancer prognosis and diagnosis that can assist decision making for cancer patient management.\n\nI have a few comments that can be useful to improve the article;\n1. The title is good. However, an alternative title is applicable and can be more meaningful as suggested below: \" Proteomic Analysis of Mammary Cancer Cells Carcinogenesis Induced by DMBA (7,12-dimethylbenc[a] in Sprague-Dawley Rats\" Since there are many species of rats, specifically indicating the types of rats used in this study in the title is reasonable. Different rats may respond differently to research methodology and the related materials used.\n2. Abstract a) Background Line 2, the word \"attack\" is less scientific and do not much reflect a pathology term (layman). It is better to change it to \"infiltrate\"...to better define the usual cellular feature of neoplastic cancer growth.\nb) Methods: I believe there is no evaluation conducted on histopathological examination (no lesion scoring). The histopathology is only descriptive to support and validate that the proteomic analysis is associated with the tumor successfully induced in the rats. Therefore the word \"evaluated\" (last line) should be replaced with \" examined\".\nc) Results: Line 6: the words \"..........from the surface to the lumen of mammary duct,....\" is unclear. Is this referring to epithelial cells lining the duct that proliferated from the basement membrane (or from the epithelial lining to the basement membrane), to the surface, that is towards the lumen of the duct? The sentence need to be reconstructed for clarity.\n3. Introduction: Sentence No 2, Line 3, \"to spread outside the mammary gland\": It is better to change these words to \"can spread to other organs and tissues\". I believe these words are more clearer and meaningful.\n3. Histopathology Image (Figure 2) a) The two images need to be labelled; Which one is A and which one is B? Left or Right? This will help any reader of this article to easily and correctly refer and relate between the details of both images.\nb) There is also no cellular description for the image of the control group rat. Since the images of both groups of rats are shown, the description of both, is necessary.\nc) The word \"hyperplasia\" is not accurate for cellular description for tumor (neoplasia). The word hyperplasia is mitosis (cellular division) of normal cells that the body cell proliferation signaling system can control. In contrary, for neoplasia, it is an uncontrolled cellular proliferation associated with carcinogens that stimulates the cellular growth. However, I believed, the hyperplasia in the figure is referring to the fibrocytes. It is also important to describe the mitotic index (high or low) of the mammary cancer cells in this study.\nd) The cellular description for the rat in the treatment group can be improved. Importantly, to include the description that strongly suggests the cellular features of malignant neoplasia (cancer), such as pleomorphism (variation in cell sizes and shapes), the mitotic index (high or low) etc. If for instance, neoplastic cells are seen present in the lumen of blood vessels and/or lymphatic vessels (tumor emboli), it would be better because this validate the tumor is malignant, knowing that, only malignant tumors can spread to other body sites (ie: an indication of not a benign tumor). However, seeing these evidences, are of rare occasion and can be exhaustive. Other supportive cellular features of malignancy (pleomorphism, high mitotic index etc.), are acceptable.\nd) Figure 3: Which one is the control and Treated group? The left or right image? Labeling is required. The legend for Figure 3 needs a more clearer description. For B, the treated group rat, if the cells are not cuboidal? What are the changes in shape when neoplastic? Describe the changes.\n\nThis is my opinion for the description of the duct in B as follows; The duct in the treated group rat is thickened and appeared eosinophilic with less discernable nuclei. The thickened duct shows reduction in size of its lumen. The duct in the control rat is single layered with visible nuclei of the epithelial cells lining the duct.\ne) Conclusion Second sentence, line 3; The words \"......were thought to be....\" can be replaced with better words like, \" suggestive of \" or \"likely\". This conclusion is based on molecular weight data analyses between the protein profiles (proteomic) of the current work and referring to previous studies.\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": []
}
] | 1
|
https://f1000research.com/articles/12-606
|
https://f1000research.com/articles/12-766/v1
|
30 Jun 23
|
{
"type": "Research Article",
"title": "Evaluation by app in smartphones of awake bruxism at the return of presential classes in two university centers",
"authors": [
"Byron Velasquez Ron",
"Veronica Mosquera Cisneros",
"Pamela Pazmiño Troncoso",
"Maria Rodriguez Tates",
"Eddy Alvares Lalvay",
"Luis Chauca Bajaña",
"Andrea Ordoñez Balladares",
"Veronica Mosquera Cisneros",
"Pamela Pazmiño Troncoso",
"Maria Rodriguez Tates",
"Eddy Alvares Lalvay",
"Luis Chauca Bajaña",
"Andrea Ordoñez Balladares"
],
"abstract": "Background. The return to normality post-pandemic brought some inconveniences to the population, especially students. To evaluate the frequency of awake bruxism behaviors through the use of an app on smartphones in dental students returning to presential classes. Awake bruxism was evaluated with the creation of an app that according to the authors evaluates: relaxed jaw muscles, dental contact, jaw effort, clenching teeth and teeth grinding, 5 frequent oral conditions in the population. The frequency of awake/daytime bruxism (AB) in healthy individuals when comparing other populations with possible risk factors for additive bruxism (psychological factors, depression, suicide delusions, etc.), evaluating consequent clinical signs (fatigue, muscle pain, attritions and dental openings). Methods: The sample of three hundred (n=300) young adults legally enrolled in two Ecuadorian universities, the sample was selected among fifth, sixth, seventh, eighth and ninth semester students legally enrolled and who are attending Faculty of Dentistry classes in 2 different cities (Quito and Guayaquil). The app was configured to provide 20 alerts during the day x seven days a week, in real time. Results. The study obtained 95% reliability and 5% error in research, was used. The relaxation condition was present in all users, but 40% of the alerts were associated with jaw and tooth discomfort, 39% corresponded to the discomfort of mandibular clenching, and 24% corresponded to tooth contact. A direct significant association was found between the state of relaxation and nonrelaxation, with a high probability of reports related to nonrelaxation (p ≤ 0.05). Conclusions: Awake bruxism with the app was evaluated, identifying 5 behaviors such as: relaxed mandibular muscles, dental contact, mandibular effort, clenching and grinding teeth, frequent conditions in the population; reporting a state of mandibular relaxation, there is a high probability that a condition of nonrelaxation would be reported (p≤0.05).",
"keywords": [
"bruxism",
"ecological momentary assessment",
"smartphone",
"prevalence",
"COVID-19 pandemic."
],
"content": "Introduction\n\nThe multifaceted clinical relationships raised by the debate on bruxism in dentistry and other professions is diverse, also controversial, arousing interest in periodic research1 on its effects and consequences. Definitions on the different types of bruxism have been agreed by expert panels (dentists, psychologists, orofacial pain experts) focusing on assessment strategies,2 the evaluation of bruxism (SB) by polysomnography (PSG), electromyography (EMG) is considerably high in research, but daytime bruxism (AB) is limited instead. “Muscle activity during wakefulness that is characterized by repetitive or sustained dental contact, accompanied by pushes or mandibular reinforcements (movements) is the current concept of awake bruxism, clarifying the concept is not necessarily pathological, however the evidence indicates clinical consequences appear.3,4\n\nThe frequency of AB in healthy individuals when comparing other populations with possible risk factors for additive bruxism (psychological factors, depression, suicide delusions, etc.), evaluating consequent clinical signs (fatigue, muscle pain, attritions and dental openings) is the evidence found, it is also recommended to evaluate intercultural comparisons that identify the influence of different social environments and habits in the lifestyle of the population that may have a diagnosis of bruxism.5,6\n\nEMA assessment allows us to see the limitations of traditional methods, such as retrospective reports questionnaires,6,7 allowing and collecting data in real time over a certain period of time by recording multiple recording points coinciding with real experiences in their environment,8–10 of great utility in diagnosis of oral activity, however the data obtained in EMA on AB are fragmented, limited to investigations that address only selected behaviors.11–13 To control this limitation, the use of smart phones to implement EMA is introduced and adapted to collect data on the signs determined in AB such as dental contact, jaw clenching, tooth compression and teeth grinding.9,14 The initial report provided by this application provides data on the frequency of GA behavior for the period of one week, for example the findings indicated 28.3%, low coefficient of variation of muscle contraction of the relaxed jaw.15\n\nThe study is proposed to demonstrate the influence of returning to presential classes affects students, through the application visualize which of the 5 signs raised is the most representative. The objective was to evaluate the frequency of AB behaviors through the use of this app on smartphones in dental students returning to presential classes.\n\n\nMethods\n\nEthical approval was granted from the Bioethics Committee of the University of the Americas (CEBE-2022-0601). Three hundred (n = 300) young adults legally enrolled in two different Ecuadorian universities (*UDLA/UESG) in Quito and Guayaquil respectively, after signing the informed consent and agreeing to be part of the study, were randomly selected after providing written informed consent and agreeing to be part of the study. They underwent a one-week registration period with a smartphone app (BruxApp, BruxApp Research®, Pontedera, Italy)16 developed by Dr Alessandro Bracci et al with the aim of reporting and monitoring the frequency of AB behaviours in an individual’s natural environment.\n\nThe sample was selected among fifth, sixth, seventh, eighth and ninth semester students (age 18-28 years old) legally enrolled and who are attending face-to-face Faculty of Dentistry classes in two different Ecuadorian universities (Quito and Guayaquil). Inclusion factors: owning smartphones in recent generations, good general health (without systemic diseases) and absence of temporomandibular joint disorder (TMD)/orofacial pain and/or any documented degenerative, neurological or systemic disease (e.g. rheumatological, hormonal). An informative meeting was held where the students maintained contact with the principal investigators (BV, VM, PP. MRT, EAL, LCH, AO).\n\nDuring that session, the objective of the study was explained, and training was provided on how to use the app (Figure 1).\n\nThe Bruxism app collects the experience of the person in a self-informed way in their daily life with an EMA approach (ecological approach), sending random messages during the day that alert the person of the conditions of their oral cavity in teeth and jaw muscles, responding within 5 minutes by touching the cone of the screen of their cell phone, Marking the current condition of the jaw muscles: relaxed jaw muscles, contact with teeth, jaw clenching, teeth clenching and teeth grinding (Figure 1).\n\nStudents are instructed to download the BruxApp app, recommending that the first data collection session commences the next morning, it is set for 20 alerts per day at random intervals, it is indicated that they must comply with at least 60% per day of replies (answered within the first 5 minutes, otherwise the screen sends an error message), Discarding from the study automatically by the app students who did not reach <60%, the data were recorded during a period of 7 days calibrating the record from 8.00 to 12.30 and from 14.30 to 22.00, subjects were instructed to ignore alerts during meals and particular activities (smoking, singing), the application records the record all day. After monitoring the seven valid days of recordings, the software generated an anonymous.csv file, which the students send to the researchers by a pre-arranged email. Data were collected by the lead author BV in collaboration with two resident dentists of the Specialty of Oral Rehabilitation VM, PP, MRT, EAL of dentistry and two professors LCH and AO of the Faculty of Dentistry of the University of Guayaquil).\n\nTo maximize the recording window, lunchtime was excluded, with the app instructing subjects to ignore alerts during meals and particular activities (smoking, singing). If the minimum number of valid responses per day was not obtained, the software automatically generated another recording day to ensure completion of the 7-day protocol.\n\n\nResults\n\nThe study obtained 95% reliability and 5% error in research, sample size of n=300 young adults from the two universities involved in the study. Table 1 shows the characterization of participants by gender.\n\nThe proportion of females among the selected sample was 84.33%, compared with 15.67% of males. Thus, the proportion of females was significantly greater than that of males in this study. It was found that 79% of the participants were aged 21 to 22 years, which was expected since this sample set consisted of young adults studying at a university (Table 2).\n\nThe relaxation condition (muscles, teeth and psychological aspects in neuromuscular stability) was evident in all users, but 40% of the alerts were associated with jaw and tooth discomfort, 39% corresponded to the discomfort of mandibular clenching, and 24% corresponded to tooth contact (Table 3).\n\n§ Jaw clenching most relevant.\n\nThus, among the aforementioned symptoms, 63% of the alerts by the BruxApp were concentrated. The study was conducted in one week, in which it was observed that on the first day, 33% of the participants reported discomfort; on the second day, 61% reported maxillary discomfort; on the third day, 64% reported decreased discomfort; on the fourth day, 21% reported a decrease in discomfort; on the fifth day, the discomfort percentage was maintained; on the sixth day, 41% of the participants reported being relaxed; and on the seventh day, the percentage of participants who reported being relaxed increased by 51%, according to the alerts reported by the BruxApp (Table 4).\n\n‡ UDLA (Universidad de Las Americas) n=180.\n\n§ USG (Universidad de Guayaquil) n=120.\n\nFor this study on daytime bruxism, the chi-square statistical test (Table 5) is considered to determine the degree of association between the condition of relaxation and nonrelaxation in the alerts collected from the app. The relaxation condition refers to the state of perceived relaxation of the jaw muscles without tooth contact. Relaxation is considered the state of relaxation perceived by the jaw muscles without occlusal contact between the teeth.\n\n† 9 boxes (36.0%) have an expected count of less than 5. The minimum expected count is 0.56.\n\nThe condition of nonrelaxation refers to the states of tooth contact, clenching of the jaw, clenching of teeth, and grinding of teeth. There is a significant direct association between the state of relaxation and nonrelaxation; when reporting a state of mandibular relaxation, there is a high probability that a condition of nonrelaxation would be reported (p≤0.05).\n\n\nDiscussion\n\nThe behavior of the AB was demonstrated in this study, the approach with EMA provided information on the frequency of the symptoms raised in the app, finding a higher percentage in women 84%, population considered young (21/22 years) 79%. The population acceptance with the use of the app on their phones, is forming part of everyday life17 adequately accepting the ecological assessment, with an average alert rate higher than 70%.\n\nGiven the different frequencies and percentages of BruxApp alerts, depending on gender, age and age groups.18 Of the sample of 300 young adults from two universities aged between 18 and 25 years, it was found that 32.13% and 5.91% of females and males, respectively, had maxillary discomfort. The alerts through the BruxApp application were useful for the study of the behavior of maxillary discomfort. Of all the alert responses, 60% were reports of a relaxed state (i.e., without maxillary discomfort). By excluding the state of relaxation from the alerts, mandibular tightening corresponded to 39% of the alerts received by BruxApp. The frequency of five specific conditions (i.e., relaxed jaw muscles, tooth contact, jaw bracing, teeth clenching, and teeth grinding) was reported over a 7-day observation period. Such an approach allowed us to collect data from the > 6000 alerts (up to 20 alerts × 300 participants × 7 days). During the observation period for 7 days, 42000 data were collected (20 alerts × 300 participants × 7 days). Alerts, varied in the 5 specific conditions incorporated in the app: relaxed jaw muscles, dental contact, jaw reinforcement, teeth clenching and teeth grinding.\n\nWe compare the findings found in studies by Zani et al. (2021) collected self-reported data at unique time points.19,20 Observational studies have as a characteristic massive collection of EMA data with referential values of frequency of the behavior of AB21 complementing with stressors associated with the return to face-to-face classes in universities. Tightening the jaw (15.28%) has the highest value in monitoring during the 7 days, the least frequent tooth pain (0.17%). The relaxed maxillary muscles 68.9%, indicates that the combined frequency of the various behaviors related to AB was 23.6%. The absence of reference values for the EMA-based frequency of AB behaviors in the literature could be considered as a reference point for future research on the epidemiological characteristics of AB in healthy young adults.22,23\n\nThe potential importance of psychological factors as etiological factors of AB, in addition to the relationship that the female gender is more prone to stress than the male gender that controls their emotions more,24 these results are related to the Bracci et al. (2018) studies and Dias et al. (2021), found a slight gender difference in the frequency of AB, with EMA evaluations not being determinant.13,24,25 The methodology used explains gender-related differences.26\n\nNo significant differences were found between the population that participated in the research (UDLA; USG), finding that is considered important in self-reported strategies for AB, which may give a high bias in the data.27 The heterogeneity of the information was limited to the minimum by the ease in the calibration of the individual and group self-report, the training given to the two populations of the study, indicate the download of the same BruxApp version, even independent of the model of smart phones.28 Being dental students the population may have positively influenced the results, having knowledge of what determines the app limited the bias in the study, we would recommend developing the same study in the general population with limited knowledge of what is being investigated.29\n\nOn the first day of alerts, 33% of the participants reported discomfort; on the second day, 61% reported maxillary discomfort; on the third day, 64% reported decreased discomfort; on the fourth day, 21% reported a decrease in discomfort; on the fifth day, the discomfort percentage was maintained; on the sixth day, 41% of the participants reported being relaxed; and on the seventh day, the percentage of participants who reported being relaxed increased by 51%, according to the alerts reported by the BruxApp. The natural fluctuation, the difficulties in the consistent recognition of the symptomatology reported the specific behaviors of the BA demonstrated a lot of variability,30 these findings indicate that the relaxed muscles are recognized in a high percentage of the population investigated, taking as a starting point of baseline results when evaluating combined frequencies in all the symptomatology of the BA indicated in the app.31,32\n\nThe EMA strategy indicated the mean frequency value estimating reliability in AB, this reduces the influence of natural fluctuation directly related to the specific symptomatology of AB.33,34 It is indicated that registration by email limits daytime contact in patients with TMD.35,36 It would be recommended that future research evaluate the increase or decrease in the frequency of BA symptoms, relating them to eating habits, smoking, medication use and psychological problems.37,38 The data can contribute to updating the definition of bruxism (2018), refinement of evaluation strategies.39,40 Population comparisons are made more accessible by the possibility of translation of the application indicating the step-by-step procedure led by mother tongue experts in the field,41,42 ongoing multicenter project on the epidemiology of bruxism.\n\n\nConclusion\n\nBruxism awake with the app was evaluated, identifying 5 behaviors such as: relaxed mandibular muscles, dental contact, mandibular effort, clenching and grinding teeth, frequent conditions in the population; reporting a state of mandibular relaxation, there is a high probability that a condition of nonrelaxation would be reported (p≤0.05).\n\nThe study was developed properly, the information obtained allowed to raise real data that indicate the relationship of stress with parafunctions (AB), the drawback we found was that some participants being a self-assessment forgot to register some alerts considering a weakness of the app. We would recommend future research with the participation of teachers.",
"appendix": "Data availability\n\nZenodo. Evaluation by app in smartphones of awake bruxism at the return of presential classes in two university centers, https://doi.org/10.5281/zenodo.7979723. 43\n\nThis project contains the following underlying data:\n\n• Table 1. docx (Data of distribution of the sample by gender)\n\n• Table 2. docx (Data of distributions of sample by age)\n\n• Table 3. docx (Data of distribution of alerts according to user conditions)\n\n• Table 4. docx (Data of distribution of alerts according to condition among sex and age groups)\n\n• Table 5. docx (Data of significance test)\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 would like to express their special thanks to Universidad de Las Américas.\n\n\nReferences\n\nEmodi A, Manfredini D, Shalev T, et al.: Awake Bruxism-Single-Point Self-Report versus Ecological Momentary Assessment. J. Clin. Med. 2021 Apr 15; 10(8): 1699. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLobbezoo F, Ahlberg J, Raphael KG, et al.: International consensus on the assessment of bruxism: Report of a work in progress. J. Oral Rehabil. 2018 Nov; 45(11): 837–844. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDe Baat C, Verhoeff M, Ahlberg J, et al.: Medications and addictive substances potentially inducing or attenuating sleep bruxism and/or awake bruxism. J. Oral Rehabil. 2021 Mar; 48(3): 343–354. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLobbezoo F, Ahlberg J, Glaros AG, et al.: Bruxism defined and graded: An international consensus. J. Oral Rehabil. 2013 Jan; 40(1): 2–4. PubMed Abstract | Publisher Full Text\n\nMatthew N, Manchery N: Can chronic oral inflammation and masticatory dysfunction contribute to cognitive impairment? Curr. Opin. Psychiatry. 2020 Mar; 33(2): 156–162. Publisher Full Text\n\nEmodi A, Manfredini D, Shalev T, et al.: Psychosocial and Behavioral Factors in Awake Bruxism-Self-Report versus Ecological Momentary Assessment. J. Clin. Med. 2021 Sep 27; 10(19): 4447. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSouza M, Carvalho A, Fugueredo O, et al.: Awake bruxism frequency and psychosocial factors in college preparatory students. Cranio. 2020 Oct 14; 1–7.\n\nBracci A, Lange M, Djukic G, et al.: Ecological momentary assessment of awake bruxism behaviors: Possible developments and clinical usefulness of a smartphone application. Front. Neurol. 2019 Mar 5; 10: 170.\n\nMarpaung C, van Selms MKA , Lobbezoo F: Prevalence and risk indicators of pain-related temporomandibular disorders among Indonesian children and adolescents. Community Dent. Oral Epidemiol. 2018 Aug; 46(4): 400–406. PubMed Abstract | Publisher Full Text\n\nBastani P, Manchery N, Samadbeik M, et al.: Digital Health in Children’s Oral and Dental Health: An Overview and a Bibliometric Analysis. Children. 2022; 9: 1039. Publisher Full Text\n\nShopova D, Bozhkova T, Yordanova S, et al.: Case Report: Digital analysis of occlusion with T-Scan Novus in occlusal splint treatment for a patient with bruxism. F1000Res. 2022; 10: 10. Publisher Full Text\n\nKaplan S, Ohrbach R: Self-Report of Waking-State Oral Parafunctional Behaviors in the Natural Environment. J. Oral Facial Pain Headache. Spring 2016; 30(2): 107–119. PubMed Abstract | Publisher Full Text\n\nDias R, Rodrigues M, Serra J, et al.: Utility of Smartphone-based real-time report (Ecological Momentary Assessment) in the assessment and monitoring of awake bruxism: A multiple-week interval study in a Portuguese population of university students. J. Oral Rehabil. 2021 Dec; 48(12): 1307–1313. PubMed Abstract | Publisher Full Text\n\nBracci A, Djukic G, Favero L, et al.: Frequency of awake bruxism behaviours in the natural environment. A 7-day, multiple-point observation of real-time report in healthy young adults. J. Oral Rehabil. 2018 Jun; 45(6): 423–429. Publisher Full Text\n\nLavigne G, Rompré P, Montplaisir J: Sleep bruxism: Validity of clinical research diagnostic criteria in a controlled polysomnographic study. J. Dent Res. 1996; 75(1): 546–552. PubMed Abstract | Publisher Full Text\n\nFunato M, Ono Y, Baba K, et al.: Evaluation of the non-functional tooth contact in patients with temporomandibular disorders by using newly developed electronic system. J. Oral Rehabil. 2014; 41(3): 170–176. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHeboyan A, Karobai M, Hamed A, et al.: Bruxism as a Consequence of Stress and Movement Disorders: Brief Review. Eur. J. Gen. Dent. 2022; 11: 081–083. Publisher Full Text\n\nManfredini D, Bracci A, Djukic G: BruxApp: the ecological momentary assessment of awake bruxism. Minerva Stomatol. 2016 Aug; 10(4): 252–255. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZani A, Lobbezoo F, Bracci A, et al.: Smartphone based evaluation of awake bruxism behaviors in a sample of healthy young adults findings from two University centers. J. Oral Rehabil. 2021 Sep; 48(9): 989–995. PubMed Abstract | Publisher Full Text | Free Full Text\n\nColonna A, Lobardo L, Siciliani G, et al.: Smartphone-based application for EMA assessment of awake bruxism: compliance evaluation in a sample of healthy young adults. Clin. Oral Investig. 2020 Apr; 24(4): 1395–1400. Publisher Full Text\n\nGoldstein R, Auclair W: The clinical management of awake bruxism. J. Am. Dent. Assoc. 2017 Jun; 148(6): 387–391. Publisher Full Text\n\nBulanda S, Ilczuk D, Nitecka A, et al.: Sleep Bruxism in Children: Etiology, Diagnosis, and Treatment-A Literature Review. Int. J. Environ. Res. Public Health. 2021 Sep 10; 18(18): 9544. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCavallo P, Carpinelli L, Savarese G: Perceived stress and bruxism in university students. BMC. Res. Notes. 2016 Dec 21; 9(1): 514. PubMed Abstract | Publisher Full Text | Free Full Text\n\nManfredini D, Serra J, Carboncini F, et al.: Current Concepts of Bruxism. Int. J. Prosthodont. September/October 2017; 30(5): 437–438. PubMed Abstract | Publisher Full Text\n\nBracci A, Djukic G, Salmaso L, et al.: Frequency of awake bruxism behaviours in the natural environment. A 7-day, multiple-point observation of real-time report in healthy young adults. J. Oral Rehabil. 2018 Jun; 45(6): 423–429. PubMed Abstract | Publisher Full Text\n\nShopova D, Mladenov K: Case Report: A digital workflow in the treatment of bruxism in a young patient. F1000Res. 2022; 10: 10. Publisher Full Text\n\nThymi M, Rollman A, Visscher C, et al.: Experience with bruxism in the everyday oral implantology practice in the Netherlands: a qualitative study. BDJ Open. 2018 Nov 9; 4: 17040. PubMed Abstract | Publisher Full Text | Free Full Text\n\nManfredini D, Ahlberg G, Bracci A, et al.: Towards a Standardized Tool for the Assessment of Bruxism (STAB)-Overview and general remarks of a multidimensional bruxism evaluation system. J. Oral Rehabil. 2020 May; 47(5): 549–556. PubMed Abstract | Publisher Full Text\n\nShopova D, Yordanova M, Yordanova S, et al.: Software Details in Occlusal Splint Creation through 3Shape Design Studio. Open Access Maced. J. Med. Sci. 2021; 9(D): 330–335. Publisher Full Text\n\nMark A: What is bruxism? J. Am. Dent. Assoc. 2021 Sep; 152(9): 788. Publisher Full Text\n\nNagappan N, Madhanmohan R, Manchery N, et al.: Oral Health-Related Quality of Life and Dental Caries Status in Children With Orofacial Cleft: An Indian Outlook. J. Pharm. Bioallied Sci. 2019 May; 11(Suppl 2): 169–S174. Publisher Full Text\n\nHardy R, Bonsor S: The efficacy of occlusal splints in the treatment of bruxism: A systematic review. J. Dent. 2021 May; 108: 103621. PubMed Abstract | Publisher Full Text\n\nDadnam D, Dadnam C, Al-Saffar H: Pandemic bruxism. Br. Dent. J. 2021 Mar; 230(5): 271. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSabbagh H, Sabbagh A, Heppner A, et al.: Patients’ perceptions on temporomandibular disorder treatment with hydrostatic oral splints - a pilot study. BDJ Open. 2022 Feb 5; 8(1): 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDuanmu Z, Liu L, Ren Y, et al.: Development of a biomechanical model for dynamic occlusal stress analysis. Int. J. Oral Sci. 2021; 13: 29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGoldstein G, DeSantis L, Goodcacre C: Bruxism: Best Evidence Consensus Statement. J. Prosthodont. 2021 Apr; 30(S1): 91–101. Publisher Full Text\n\nManfredini D, Colonna A, Bracci A, et al.: Bruxism: a summary of current knowledge on aetiology, assessment and management. Oral Surg. 2020; 13(4): 358–370. Publisher Full Text\n\nYouny S, Salinas T, Wiens J: The effect of patient specific factors on oclussal forces generated: best evidence consensus statement. J. Prosthodont. 2021; 30(S1): 52–60. Publisher Full Text\n\nMalvin N, Lobbezzo F, Karen S, et al.: Stress-evoked muscle activity in women with and without chronic myofascial face pain. J. Oral Rehabil. 2021; 48: 1089–1098.\n\nPereira N, Oltramari, Conti P, et al.: Frequency of awake bruxism behaviour in orthodontic patients: Randomised clinical trial: Awake bruxism behaviour in orthodontic patients. J. Oral Rehabil. 2021 Apr; 48(4): 422–429. PubMed Abstract | Publisher Full Text\n\nSilva T, Ortiz F, Maracci L, et al.: Association among headache, temporomandibular disorder, and awake bruxism: A cross-sectional study. Headache. 2022 Jun; 62(6): 748–754. Publisher Full Text\n\nVelásquez Ron B, Mosquera Cisneros V, Pazmiño Troncoso P, et al.: Monitoring of awake bruxism by intelligent app. F1000Res. 2022; 11: 479. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVelasquez Ron B, Rodriguez Tates M: Evaluation by app in smartphones of awake bruxism at the return of presential classes in two university centers. Zenodo. F1000Res. 2023; 1(23): 215.Publisher Full Text"
}
|
[
{
"id": "224184",
"date": "14 May 2024",
"name": "Maria Beatriz Duarte Gaviao",
"expertise": [
"Reviewer Expertise Oral Physiology",
"Temporomandibular disorders",
"Brruxism",
"Quality of life."
],
"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 aimed to evaluate the awake bruxism in university students using a smartphone application. This is an important and interesting issue, the sample is adequate and the authors have looked for a good methodology. Nevertheless, the manuscript needs reworking to be more comprehensible. In general, the English language needs to be revised. Furthermore, cited references must be checked for the names of the authors and their respective numbers throughout the text, synchronized with the list of references. Abstract: The “Background” does not make sense. Please, rewrite and defined the aim precisely. Also define the app used, BruxApp app, so as not to confuse the reader. The phrase “Awake bruxism was evaluated with the creation of an app that according to the authors evaluates…” it seems that the authors of this manuscript created the app. It is not possible to understand what additive bruxism is. The conclusion repeats the results and is vague.\nText Please, revised the English language in the Introduction, as commented above. Almost paragraphs need to be rewritten, specially the last one, in which the first sentence does not make sense considering the study design, since the AB was not evaluated before or during the pandemic. Moreover, the aim needs to be better described and conclusion must be in agreement. Please, check if the BruxApp was developed by Dr Alessandro Bracci et al. The reference 16 does not match with this information, as well as the authors of reference 16 did not developed the app, I think. Statistical analysis must be inserted in the end of Methods. Please, explain why the condition of relaxation and nonrelaxation was associated. Why is this association important? Many paragraphs of the Discussion are results, not characterizing discussion. The Conclusion is not reliable, since stress with parafunctions were not evaluated. Finally, the manuscript needs intense reformulation regarding the design, aim, results and their interpretation, and a more precise discussion and conclusion. Despite this, the authors have performed a good job using an expressive sample.\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": [
{
"c_id": "11901",
"date": "05 Aug 2024",
"name": "Byron Velasquez Ron",
"role": "Author Response",
"response": "Dear Mr. Editor, after the corrections recommended by the reviewers and yours, we present an Original Research article entitle Monitoring the frequency of awake bruxism behaviors in dental students from two university centers by using a smartphone app, for consideration by F1000reserach . We confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. In this paper was to monitor the frequency of awake bruxism behaviors in dental students by using a smartphone app. We attach the comments of the reviewers and the new manuscript with all the changes made. We believe that this manuscript is appropriate for publication by F1000reserach. Reviewed 1 : Maria Beatriz Duarte Gaviao Please, revised the English language in the Introduction, as commented above. Almost paragraphs need to be rewritten, specially the last one, in which the first sentence does not make sense considering the study design, since the AB was not evaluated before or during the pandemic. Moreover, the aim needs to be better described and conclusion must be in agreement. Please, check if the BruxApp was developed by Dr Alessandro Bracci et al. The reference 16 does not match with this information, as well as the authors of reference 16 did not developed the app, I think. Statistical analysis must be inserted in the end of Methods. Please, explain why the condition of relaxation and non relaxation was associated. Why is this association important? Many paragraphs of the Discussion are results, not characterizing discussion. The Conclusion is not reliable, since stress with parafunctions were not evaluated. Finally, the manuscript needs intense reformulation regarding the design, aim, results and their interpretation, and a more precise discussion and conclusion. Despite this, the authors have performed a good job using an expressive sample. Response to comments from reviewers: English language reviewed Cites references reviewed Introduction totally changed Aim changed The Bracci Team created the app (Siena University) References 16 corrected. Statistical analysis changed the order Relaxation and non-relaxation were associated, the app allows in its monitoring to decipher if the patient is relaxed, in some cases the patient does not accept that he is not relaxed, the monitoring clarifies that on some occasions he may be asymptomatic and therefore does not know the condition. Discussion totally changed Conclusion totally changed Reviewer 2 : Swapna B V This manuscript aims to evaluate the use of smartphone applications in university students with awake bruxism. Abstract- The background is not clear and needs to be rewritten more meaningfully. Please re-write the aim of the study and the conclusion. In introduction, the abbreviation SB is for sleep bruxism, but it is wrongly mentioned. There are other abbreviations that have not been expanded, eg. EMA, GA. Please check whether the use of terminologies like pushes or mandibular reinforcement, additive bruxism is appropriate. The methodology of this study is interesting as the tool used for evaluation is gaining popularity, however the manuscript needs to be improvised and more comprehending to improve the readership. The English language requires lot of corrections and improvement as most of the sentences do not convey the intended meaning to the reader. The reference number 16 cited is not by Dr Alessandro Bracci, about development of the app, It is wrongly cited. Is the app available as free version for download? How did the researcher persuade the respondents to download it? What is the full form of BA, mentioned in discussion? The reference number 24, 25 does not match with information about gender differences. The conclusion should be rewritten as this sentence “Bruxism awake with the app was evaluated, identifying 5 behaviors such as’’ makes no sense. Response to comments from reviewers: Abstract totally changed Aim changed Conclusion totally changed SB corrected Abbreviation reviewed The manuscript is corrected English language reviewed References 16 corrected. For academic purposes the app is free, a letter from the institution must be sent that proves the study to be carried out. The participants were socialized about their ailments, as they did not know the subject and explained to them, the study aroused a lot of interest. BA changed for AB (awake bruxism) References 24,25 reviewed Conclusion totally changed"
}
]
},
{
"id": "224191",
"date": "14 May 2024",
"name": "Dobromira Antonova Shopova",
"expertise": [
"Reviewer Expertise I am a prosthodontics.I am interested in digital technologies in dentistry - additive manufacturing and milling CAD/CAM. I also started working in the field of implantology."
],
"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 work is clearly and accurately presented and it cites the current literature properly. The study design is appropriate and the work is with technically and scientifically sound. The sufficient details of methods and analysis provide to allow replication by other researchers. The statistical analysis and its interpretation are appropriate. All the source data underlying the results are available to ensure full reproducibility. The conclusions are adequately drawn and supported by the results. 1. The introduction is short, with only 17 cited authors. In general, the number of references is not large - 50, which tends to the minimum for a review article. I ask the authors to add more articles, especially those published in the last 5 years. Authors can add and more similar articles to enrich their article. 50 cited articles are too small number. 2. Long tables make the results quite difficult. Try to systematize the cited authors more tightly. 3. The discussion is voluminous enough and a sufficient number of authors are compared. 4. The conclusion consists of one short sentence. Authors can submit their opinion on the most suitable app according to them.\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": "274092",
"date": "22 May 2024",
"name": "Swapna B V",
"expertise": [
"Reviewer Expertise Prosthodontics"
],
"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 aims to evaluate the use of smartphone applications in university students with awake bruxism.\nAbstract- The background is not clear and needs to be rewritten more meaningfully. Please re-write the aim of the study and the conclusion.\nIn introduction, the abbreviation SB is for sleep bruxism, but it is wrongly mentioned. There are other abbreviations that have not been expanded, eg. EMA, GA. Please check whether the use of terminologies like pushes or mandibular reinforcement, additive bruxism is appropriate.\nThe methodology of this study is interesting as the tool used for evaluation is gaining popularity, however the manuscript needs to be improvised and more comprehending to improve the readership. The English language requires lot of corrections and improvement as most of the sentences do not convey the intended meaning to the reader.\nThe reference number 16 cited is not by Dr Alessandro Bracci, about development of the app, It is wrongly cited. Is the app available as free version for download? How did the researcher persuade the respondents to download it?\nWhat is the full form of BA, mentioned in discussion? The reference number 24, 25 does not match with information about gender differences.\nThe conclusion should be rewritten as this sentence “Bruxism awake with the app was evaluated, identifying 5 behaviors such as’’ makes no sense.\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? 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": [
{
"c_id": "11901",
"date": "05 Aug 2024",
"name": "Byron Velasquez Ron",
"role": "Author Response",
"response": "Dear Mr. Editor, after the corrections recommended by the reviewers and yours, we present an Original Research article entitle Monitoring the frequency of awake bruxism behaviors in dental students from two university centers by using a smartphone app, for consideration by F1000reserach . We confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. In this paper was to monitor the frequency of awake bruxism behaviors in dental students by using a smartphone app. We attach the comments of the reviewers and the new manuscript with all the changes made. We believe that this manuscript is appropriate for publication by F1000reserach. Reviewed 1 : Maria Beatriz Duarte Gaviao Please, revised the English language in the Introduction, as commented above. Almost paragraphs need to be rewritten, specially the last one, in which the first sentence does not make sense considering the study design, since the AB was not evaluated before or during the pandemic. Moreover, the aim needs to be better described and conclusion must be in agreement. Please, check if the BruxApp was developed by Dr Alessandro Bracci et al. The reference 16 does not match with this information, as well as the authors of reference 16 did not developed the app, I think. Statistical analysis must be inserted in the end of Methods. Please, explain why the condition of relaxation and non relaxation was associated. Why is this association important? Many paragraphs of the Discussion are results, not characterizing discussion. The Conclusion is not reliable, since stress with parafunctions were not evaluated. Finally, the manuscript needs intense reformulation regarding the design, aim, results and their interpretation, and a more precise discussion and conclusion. Despite this, the authors have performed a good job using an expressive sample. Response to comments from reviewers: English language reviewed Cites references reviewed Introduction totally changed Aim changed The Bracci Team created the app (Siena University) References 16 corrected. Statistical analysis changed the order Relaxation and non-relaxation were associated, the app allows in its monitoring to decipher if the patient is relaxed, in some cases the patient does not accept that he is not relaxed, the monitoring clarifies that on some occasions he may be asymptomatic and therefore does not know the condition. Discussion totally changed Conclusion totally changed Reviewer 2 : Swapna B V This manuscript aims to evaluate the use of smartphone applications in university students with awake bruxism. Abstract- The background is not clear and needs to be rewritten more meaningfully. Please re-write the aim of the study and the conclusion. In introduction, the abbreviation SB is for sleep bruxism, but it is wrongly mentioned. There are other abbreviations that have not been expanded, eg. EMA, GA. Please check whether the use of terminologies like pushes or mandibular reinforcement, additive bruxism is appropriate. The methodology of this study is interesting as the tool used for evaluation is gaining popularity, however the manuscript needs to be improvised and more comprehending to improve the readership. The English language requires lot of corrections and improvement as most of the sentences do not convey the intended meaning to the reader. The reference number 16 cited is not by Dr Alessandro Bracci, about development of the app, It is wrongly cited. Is the app available as free version for download? How did the researcher persuade the respondents to download it? What is the full form of BA, mentioned in discussion? The reference number 24, 25 does not match with information about gender differences. The conclusion should be rewritten as this sentence “Bruxism awake with the app was evaluated, identifying 5 behaviors such as’’ makes no sense. Response to comments from reviewers: Abstract totally changed Aim changed Conclusion totally changed SB corrected Abbreviation reviewed The manuscript is corrected English language reviewed References 16 corrected. For academic purposes the app is free, a letter from the institution must be sent that proves the study to be carried out. The participants were socialized about their ailments, as they did not know the subject and explained to them, the study aroused a lot of interest. BA changed for AB (awake bruxism) References 24,25 reviewed Conclusion totally changed"
},
{
"c_id": "11902",
"date": "26 Jun 2024",
"name": "Byron Velasquez Ron",
"role": "Author Response",
"response": "Dear Mr. Editor, after the corrections recommended by the reviewers and yours, we present an Original Research article entitle Monitoring the frequency of awake bruxism behaviors in dental students from two university centers by using a smartphone app, for consideration by F1000reserach . We confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. In this paper was to monitor the frequency of awake bruxism behaviors in dental students by using a smartphone app. We attach the comments of the reviewers and the new manuscript with all the changes made. We believe that this manuscript is appropriate for publication by F1000reserach. Response to comments from reviewers: Reviewer 2 . This manuscript aims to evaluate the use of smartphone applications in university students with awake bruxism. Abstract- The background is not clear and needs to be rewritten more meaningfully. Please re-write the aim of the study and the conclusion. In introduction, the abbreviation SB is for sleep bruxism, but it is wrongly mentioned. There are other abbreviations that have not been expanded, eg. EMA, GA. Please check whether the use of terminologies like pushes or mandibular reinforcement, additive bruxism is appropriate. The methodology of this study is interesting as the tool used for evaluation is gaining popularity, however the manuscript needs to be improvised and more comprehending to improve the readership. The English language requires lot of corrections and improvement as most of the sentences do not convey the intended meaning to the reader. The reference number 16 cited is not by Dr Alessandro Bracci, about development of the app, It is wrongly cited. Is the app available as free version for download? How did the researcher persuade the respondents to download it? What is the full form of BA, mentioned in discussion? The reference number 24, 25 does not match with information about gender differences. The conclusion should be rewritten as this sentence “Bruxism awake with the app was evaluated, identifying 5 behaviors such as’’ makes no sense. Response to comments from reviewers: Abstract totally changed Aim changed Conclusion totally changed SB corrected Abbreviation reviewed The manuscript is corrected English language reviewed References 16 corrected. For academic purposes the app is free, a letter from the institution must be sent that proves the study to be carried out. The participants were socialized about their ailments, as they did not know the subject and explained to them, the study aroused a lot of interest. BA changed for AB (awake bruxism) References 24,25 reviewed Conclusion totally changed"
}
]
}
] | 1
|
https://f1000research.com/articles/12-766
|
https://f1000research.com/articles/13-883/v1
|
05 Aug 24
|
{
"type": "Research Article",
"title": "Taxonomy of interventions at academic institutions to improve research quality",
"authors": [
"Alexandra R Davidson",
"Virginia Barbour",
"Shinichi Nakagawa",
"Alex O Holcombe",
"Fiona Fidler",
"Paul P Glasziou",
"Virginia Barbour",
"Shinichi Nakagawa",
"Alex O Holcombe",
"Fiona Fidler",
"Paul P Glasziou"
],
"abstract": "Background Research waste has become an increasing issue for research institutions and researchers due to poor research reproducibility and replicability. Interventions to improve research quality at research institutions are important to reduce research waste. This review aims to identify and classify possible interventions to improve research quality, reduce waste, and improve reproducibility and replicability within research-performing institutions.\n\nMethods Steps to develop the taxonomy were 1) Use an exemplar paper looking at journal-level interventions to improve research quality, 2) Adapt intervention titles to align with Michie’s behaviour change wheel, 3) Conduct a 2-stage search in PubMed using seed articles and reviews, and a forward and backward citation search to identify articles that evaluated or described the implementation of interventions to improve research quality, 4) Pilot draft taxonomy with researchers at an openscience conference workshop, and 5) Iterative drafting and revisions by the research team.\n\nResults Overall, 93 individual interventions were identified through the peer-review literature and researcher reporting. Eleven peer-reviewed articles were identified. Interventions identified covered research stages from before, during, and after study conduct, and whole of institution. Types of intervention included: Tools, Education & Training, Incentives, Modelling and Mentoring, Review & Feedback, Expert involvement, and Policies & Procedures. The taxonomy identified areas for research institutions to focus on to improve research quality, reproducibility, and replicability.\n\nConclusions Areas of focus and future research include improving incentives to implement quality research practices, evaluating current interventions, encouraging no- or low-cost and high-benefit interventions, examining institution culture and individual research ethos, and encouraging researcher mentor-mentee relationships.",
"keywords": [
"Academies and Institutes",
"research quality",
"reproducibility",
"reproducibility of results",
"replicability",
"taxonomy"
],
"content": "Introduction\n\nOver the past decade, the problems of research waste and the reproducibility crisis have been extensively documented.1–4 In 2014, a 5-part series in the Lancet found that approximately 85% of biomedical research goes to waste through the combination of poor study design, non-publication, and poor reporting,1 with a similar percentage recently reported for ecology research.5 Studies in disciplines as diverse as economics, cancer biology, psychology, machine learning, ecology, and social sciences have found disappointingly low reproducibility and replicability.1–4\n\nLow reproducibility means that original protocol, materials or data sets may not be available to conduct analysis to reproduce the results; low replicability relates to the inability to re-conduct or re-conduct well an entire study or experiment, regardless of whether the results replicate.6 The two issues, reproducibility and replicability, exist on a spectrum from ‘direct’ that stritly follow the original methods, to ‘conceptual’ where researchers may selectively alter aspects of the original methods to test for robustness and generalisability.7,8 Both are important to reducing research waste and improving overall research practice quality.\n\nPoor research reproducibility and replicability is partly attributable to flaws in study design and partly to incomplete or poor documentation of research processes. The flow-on effects impact research users such as industry. Many of these problems are avoidable and might be reduced with sustained interventions by research institutions. Some key stakeholders in improving the research system to improve quality are researchers, journals, and research funders, as well as research institutions. While this paper focuses on research institutions, the findings are relevant to the other stakeholders.\n\nWhat might research institutions do to improve the quality and reproducibility of their research? This work builds on a taxonomy of interventions for journals and publishers developed by Blanco et al in their scoping review of interventions to improve adherence to reporting guidelines in health research, which classifies interventions by the type of intervention and by the research stage.9 The current taxonomy expands the behaviour change categories used by Blanco, drawing on Michie’s behaviour change wheel which covers Training, Incentivisation, Modelling, Persuasion, Education, and Coercion. This taxonomy is useful, not just for identifying existing interventions, but also to identify where there are gaps. The taxonomy of interventions will serve several purposes: (i) to assist with search and classification in scoping reviews, (ii) to enable systematic reviews on specific topics – which may be a cell, row, or column of the taxonomy table, and (iii) to help prioritize the development and evaluation of additional interventions in institutions. This review aims to develop a taxonomy of possible interventions to improve research quality, reduce waste, and improve reproducibility and replicability within research-performing institutions. To assist this process, we first aimed to identify and classify published and unpublished examples, including studies that assessed the interventions.\n\n\nMethods\n\nA preprint of this paper is available on bioRxiv: https://www.biorxiv.org/content/10.1101/2022.12.08.519666v1.10 Research institutions were inclusive of academic institutions such as universities, government research institutes, and privately funded institutions. Within institutions, interventions could occur at a range of levels, from actions by individuals to actions by departments and whole institutions, including policy changes.\n\nThe interventions could be training or education, institutional incentives or regulations, or provision of infrastructure and tools; the only requirement was that the intervention must be aimed at some aspect of reducing research waste, improving quality, or improving reproducibility. For example, interventions aimed at better study design or better conduct of research, increased or timelier publication of research, better reporting of research, including better ‘open science’ such as the provision of protocols and other research process details, and research data would all be in scope.\n\nBecause the potential range of potential interventions and terms used was broad and unknown, we used a 2-stage process for the search. Stage 1 used a set of seed articles and reviews identified by the authors from a preliminary search which identified several articles including a review of journal interventions. We then used a forward and backward citations search of this set of articles to widen the pool of potential articles. Stage 2 then conducted a word frequency analysis on these eligible articles to identify key terms to build a search strategy for the full database searches.\n\nThis Stage 1 search identified a key review article on interventions to improve adherence to reporting guidelines for journals, which included a suggested taxonomy.9 We then drafted an initial taxonomy and used the other interventions identified from the searches to test and modify this proposed intervention taxonomy.\n\nIn this next stage, we sought input from others regarding the taxonomy and for further examples of interventions. To ensure the taxonomy was reflective of research practice in institutions, we invited possible end-users to assist in co-development using aspects of participatory design research.11 During the 2021 Association for Interdisciplinary Meta-Research and Open Science Conference (https://www.ivvy.com.au/event/aimos2021), we held a workshop with approximately 40 participants to further refine the draft taxonomy. Detail on the audience involvement in the development of the taxonomy was outlined in the conference schedule, and attendees were informed that their contributions would add to the development of the taxonomy. Workshop participants included ~30 researchers at different career levels, ranging from PhD students to professors.\n\nBriefly, the steps of the workshop process were:\n\n1. List any interventions you have conducted, attended, or heard of.\n\n2. Map these interventions onto the taxonomy, using a Google Doc accessible to all participants (Note: if they do not fit, then put them into a second list)\n\n3. Discussion of interventions that do not fit the proposed taxonomy (do these warrant a change to the taxonomy?)\n\n4. General discussion on next steps (reviewing and applying feedback and opportunity to contribute in future rounds of revision and authorship).\n\nFollowing the workshop, we used the participant input to develop the revised taxonomy, collect further potential examples, and revise the taxonomy again. In the following year, the taxonomy was presented at the 2022 Association for Interdisciplinary Meta-Research and Open Science Conference (https://aimos.community/aimos2022), where authors asked for any final feedback. No conference attendees responded to this. Ethics approval was not required as the process involved negligible risk, and the de-identified workshop participants were all sent a draft copy and invited to be authors on the manuscript. No workshop participants responded to the invitation.\n\n\nResults\n\nInterventions were first classified according to the research stage of their implementation: before study conduct, during study conduct, and after study conduct. Research stages were then further subclassified into education, grant writing, protocol writing, research conduct & analysis, manuscript writing, manuscript submission, or post-publication. Table 1 highlights which type of behaviour change interventions, as classified by Michie’s behaviour change wheel, are represented at each research stage.\n\n‘Whole of institution’ was included as an additional category, separate to the research stages, as some interventions relate to two or more stages of research or support overall research practices in that institution. Similarly, ‘Institutional Culture and Individual Ethos’ was added to the taxonomy to highlight the influence of the culture of the institution including their overall research aims and mission, and those that work in the institution and their individual ethos, values, and attitudes towards research practices.\n\nTable 1 gives examples of the interventions identified. The full set of interventions are displayed at the Open Science Framework website (“Taxonomy of interventions at academic institutions to improve research quality - Full Taxonomy Table and Example Interventions” Overall, we identified 93 different possible interventions).\n\nThe types of interventions varied widely, from whole of institution policies – such as modifying hiring and promotion criteria to emphasise rigorous research design, reproducibility, and transparency, to highly specific departmental-level interventions such as developing mentor-mentee relationships. Most interventions are applicable to researchers at all levels of experience. Several interventions are specific to particular areas of research e.g., registration of clinical trials in healthcare, but others, such as mentoring, or journal clubs are relevant to multiple disciplines. We did not subclassify by disciplines.\n\nIn reviewing the taxonomy, several themes emerged. Many of the interventions require a substantial and long-term investment in people– e.g., hiring of specific experts; training of research assistants and others on data collection methods and techniques; co-design with patients and public/end-users. Though ad hoc seminars have value, most of the interventions require individuals or teams or to be embedded in institutions, even if the intervention is to provide ‘just in time’ advice. For example, a publications officer to check adherence of papers to reporting guidelines might have to be well established for them to be able to provide on the spot advice at a time of need.\n\nEducation of researchers and research support staff can happen by a variety of formal and informal methods. There was some suggestion that some of the training had to be compulsory e.g., included in the curriculum for undergraduate and postgraduate research training. However, there was also specific recognition of the role of informal networks including peer-to-peer learning and mentor-mentee relationships. We note that mentor-mentee learnings can be in both directions, as more junior staff are sometimes the instigators of novel research practices learned during their research skill development. As training in undergraduate and postgraduate programs are constantly changing, more experienced researchers can be exposed to this by mentoring a student or Early Career Researcher.\n\nThere were surprisingly few technical interventions suggested. Most of these also included an element of human intervention e.g., use of pull-requests and code commentary by collaborators and/or external peers on shared codebases. Notably one of the technical interventions was to cease subsidising (through purchase of site licenses) the use of certain software programs (e.g., statistical and spreadsheet) that are not conducive to reproducibility, and to instead promote and encourage the use of open science source software and practices.\n\nSurprisingly, the ‘incentives’ row has more empty cells than the other rows. This indicates either a lack of awareness of participants involved in reviewing the taxonomy, and/or a lack of incentives being implemented and available at research institutions to encourage researchers to participate in quality research practices.\n\nFollowing the classification, we searched for papers that had described and/or assessed these interventions. During the search processes, eleven articles evaluating interventions were found. All the interventions that had been assessed were in the manuscript and grant writing or education phase of research (Table 2).\n\n\nDiscussion\n\nTo improve institutional interventions that might improve research quality, an understanding of the range and types of interventions is vital. Based on work from Blanco et al (2019) in their scoping review of interventions to improve adherence to reporting guidelines in health research we have developed a taxonomy of possible interventions to improve research quality and reproducibility within institutions. At the institutional level, interventions are possible at all stages of research and for each stage of research there are several possible interventions. In this section, we relate key lessons from the taxonomy development for the Australian research context, and then touch on the broader global research environment.\n\nThrough an iterative crowdsourced process, we identified interventions that the authors or the hackathon participants had experienced, that they had seen conducted in their or others’ institutions, or which they wanted to see. Very few of the interventions have been evaluated. In several areas where interventions are possible none were identified, or the interventions suggested are only aspirational at this point.\n\nA recent Australian Chief Scientist declared a need to ‘shift from quantity to quality’ and to challenge the status quo of ‘a passive apprenticeship system’ of researcher training.12,13 Research quality has become a much-discussed topic in Australia, and internationally, but there is no systematic approach to improving research quality, especially regarding what interventions are needed at institutions. In Australia, research quality is most prominently assessed through the Excellence in Research for Australia (ERA) process. However, ERA assesses research outputs, not any part of the research process. An increased national focus on research quality more widely through the work of the National Health and Medical Research Council’s (NHMRC) Research Quality Steering Committee (RQSC) established in 2018. In 2019, the RQSC oversaw a survey of Australian Research institutions and researchers.14 Key opportunities identified from that survey relevant to interventions at institutions were the need for effective training and mentorship (especially of junior researchers) about responsible research practice; addressing factors that adversely affect research quality, such as poor research practices; promoting positive initiatives and processes rather than competition where possible; and encouraging more rigorous reproducibility procedures.\n\nIn Australia’s recently released National Research Infrastructure RoadMap, the importance of research quality is recognised in specific, limited areas, primarily data e.g., ‘An important driver for maintaining quality research output is Australia’s ability to generate and analyse data as well as improving the digital skills of researchers’.14,15 On a global level, the United Nations Educational, Scientific and Cultural Organization (UNESCO), developed their Recommendation on Open Science in 2021.16 Their recommendations align with the taxonomy in this paper as they recommend interventions related to institutions, including open scientific publications, research data, educational resources, source software and source code, and hardware. Open scientific publications relate to the ‘Education and Training’ – ‘Manuscript Submission’ cell – training on how to identify open access journals, and access funds for publication fees if necessary. Open research data relates to many of the examples provided in the ‘Research Conduct & Analysis’ column of the taxonomy, including shared version control repositories, and data dictionaries. Open educational resources includes the examples in the ‘Education and Training’ row of the taxonomy, including the availability of training sessions to have hybrid delivery. Open source software and code is included in the ‘Tools’ row. Lastly, Open hardware relates to ‘training manuals/data collection protocol, including use of equipment’ in the ‘Research Conduct & Analysis’ – ‘Education and Training’ cell.\n\nThere have been other classifications of potential interventions, the Michie behaviour change wheel and the Nosek pyramid.3,17 Both of those classifications align with ours in that they range from interventions that are simply a change in the environment – our ‘tools’, Nosek’s ‘make it easy’, Michie’s ‘enablement’ through to required actions - our ‘policies and procedures’, Nosek’s ‘make it required’, Michie’s ‘coercion’. What the classifications all demonstrate is the need for a range of approaches. By mapping interventions to specific research stage and interventions type, we have demonstrated the range of possible interventions, where there are gaps and especially the relative lack of assessment of these interventions.\n\nThe interventions in the taxonomy we present are not a comprehensive list of all possible interventions. We did not assess adherence to any of the interventions or examine their effectiveness, except where there were previously published papers. However, a recent review protocol has been published by a group of authors who aim to identify such interventions that investigate research reproducibility and replicability.18 As the participants and authors were largely or exclusively from the sciences, the list of interventions may not include interventions within Humanities and Social Sciences.\n\nA strength of this research is the use of both published peer-reviewed literature and end-user engagement to develop the taxonomy.\n\nGiven most interventions outlined in the taxonomy have not been evaluated for their impact on research quality and reproducibility, there is a clear need for more institutional interventions be evaluated. Priority areas for evaluation should be those currently in common use at institutions, to assess their value. Implementation of new or different interventions could be those that are no- or low-cost, such as open access tools and software to enhance research practices, e.g., Overleaf, and JASP, and adaptation of policies and the research environment to promote open science practices.\n\nInstitution culture and individual researcher ethos have a strong influence over the reproducibility, quality, and transferability of research practices. The UK Reproducibility Network encourages institutions to examine their research culture and how it may or may not be supportive of producing robust and credible research.19 The implementation and evaluation of interventions outlined in our taxonomy should be considered along with the institution’s current culture and potential shifts that could be made to encourage and promote open science practices.\n\nFinally, it is vital to explore the paucity of ‘incentive’ interventions that were identified. Incentivisation is important in workload models of research institutions, much like universities have incentives for their education and teaching of degrees and coursework, they need incentives for research quality. The kind of incentives depend heavily on the institutional structures and availability of resources to create or fund incentives. It is recommended that future research could be guided by this taxonomy further to identify how incentivisation of quality research practices could be better implemented.\n\n\nEthics and consent\n\nEthics approval was not applicable for this research. Implied consent was obtained when participants attended the workshop, where the conference workshop description detailed the use of knowledge created for research purposes, and this was verbally confirmed by authors in the workshop.",
"appendix": "Data availability\n\nOSF: Taxonomy of interventions at academic institutions to improve research quality - Full Taxonomy Table and Example Interventions. https://doi.org/10.17605/OSF.IO/GFW72\n\nThis project contains the following extended data:\n\n• Table 1 Outline of classification of interventions and their relationship to research stage_condensed version of taxonomy.pdf\n\n• Taxonomy of interventions at academic institutions to improve research quality_Full Taxonomy and Example Interventions.pdf\n\n• Taxonomy of interventions at academic institutions to improve research quality_Full Taxonomy and Example Interventions_V1.1.pdf\n\n• Video abstract_Taxonomy of interventions at academic institutions to improve research quality.mp4\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nAs this paper did not use traditional review methods, a reporting guideline was not used.\n\n\nAcknowledgements\n\nThe authors would like to thank the AIMOS 2021 Conference Hackathon Workshop attendees who participated in providing feedback for the draft taxonomy. The authors would also like to thank Dr Jennifer L Beaudry from Flinders University for her pre-submission peer-review of the manuscript.\n\n\nReferences\n\nGlasziou P, Altman DG, Bossuyt P, et al.: Reducing waste from incomplete or unusable reports of biomedical research. Lancet. 2014; 383(9913): 267–276. Publisher Full Text\n\nErrington TM, Iorns E, Gunn W, et al.: An open investigation of the reproducibility of cancer biology research. elife. 2014; 3: e04333. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAarts A, Anderson J, Anderson C, et al.: PSYCHOLOGY. Estimating the reproducibility of psychological science. Science (American Association for the Advancement of Science). 2015; 349(6251): aac4716. Publisher Full Text\n\nPurgar M, Klanjscek T, Culina A: Identify, quantify, act: tackling the unused potential of ecological research.2021.\n\nPurgar M, Klanjscek T, Culina A: Quantifying research waste in ecology. Nat. Ecol. Evol. 2022; 6(9): 1390–1397. Publisher Full Text\n\nBarba LA: Terminologies for reproducible research. arXiv preprint arXiv:180203311. 2018.\n\nNational Academies of Sciences E, and Medicine; Policy and Global Affairs; Committee on Science, Engineering, Medicine, and Public Policy; Board on Research Data and Information; Division on Engineering and Physical Sciences; Committee on Applied and Theoretical Statistics; Board on Mathematical Sciences and Analytics; Division on Earth and Life Studies; Nuclear and Radiation Studies Board; Division of Behavioral and Social Sciences and Education; Committee on National Statistics; Board on Behavioral, Cognitive, and Sensory Sciences; Committee on Reproducibility and Replicability in Science. Understanding Reproducibility and Replicability: Reproducibility and Replicability in Science. Washington (DC): National Academies Press (US); 2019.\n\nFidler FW, John: Reproducibility of Scientific Results. Stanf. Encycl. 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Publisher Full Text\n\nUK Reproducibility Network Steering Committee: From grassroots to global: A blueprint for building a reproducibility network. PLoS Biol. 2021; 19(11): e3001461. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBarnes C, Boutron I, Giraudeau B, et al.: Impact of an online writing aid tool for writing a randomized trial report: the COBWEB (Consort-based WEB tool) randomized controlled trial. BMC Med. 2015; 13: 221. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBöschen I: Evaluation of JATSdecoder as an automated text extraction tool for statistical results in scientific reports. Sci. Rep. 2021; 11(1): 19525. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBurns KEA, Caon E, Dodek P: Evaluation of an Internal Review Process for Grants And Manuscripts in the Canadian Critical Care Trials Group. Can. Respir. J. 2014; 21: 283–286. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChauvin A, Ravaud P, Moher D, et al.: Accuracy in detecting inadequate research reporting by early career peer reviewers using an online CONSORT-based peer-review tool (COBPeer) versus the usual peer-review process: a cross-sectional diagnostic study. BMC Med. 2019; 17: 205. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGattrell W, Hopewell S, Young K, et al.: Professional medical writing support and the quality of randomised controlled trial reporting: a cross-sectional study. BMJ Open. 2016; 6: e010329. undefined. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHawwash D, Sharp MK, Argaw A, et al.: Usefulness of applying research reporting guidelines as Writing Aid software: a crossover randomised controlled trial. BMJ Open. 2019; 9: e030943. undefined. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHirschey R, Rodgers C, Hockenberry MJ: A Program to Enhance Writing Skills for Advanced Practice Nurses. J. Contin. Educ. Nurs. 2019; 50: 109–114. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNuijten MB, Polanin JR: \"statcheck\": Automatically detect statistical reporting inconsistencies to increase reproducibility of meta-analyses. Res. Synth. Methods. 2020; 11(5): 574–579. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShanahan D, de Sousa IL , Marshall DM: Simple decision-tree tool to facilitate author identification of reporting guidelines during submission: a before–after study. Res. Integr. Peer Rev. 2017; 2: 20. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStruthers C, Harwood J, de Beyer JA , et al.: GoodReports: developing a website to help health researchers find and use reporting guidelines. BMC Med. Res. Methodol. 2021; 21(1): 217. PubMed Abstract | Publisher Full Text | Free Full Text\n\nToelch U, Ostwald D: Digital open science—Teaching digital tools for reproducible and transparent research. PLoS Biol. 2018; 16(7): e2006022-e. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "311811",
"date": "22 Aug 2024",
"name": "Charlotte R. Pennington",
"expertise": [
"Reviewer Expertise Open science",
"meta-research",
"replication."
],
"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\nOverview and main concerns:\nThis paper aims to provide a taxonomy of possible interventions to improve research quality, reduce waste, and improve reproducibility and replicability within research-performing institutions. The authors state that, through an iterative process of 5 stages, they identified 93 individual interventions and 11 supporting peer-reviewed articles. They state in the Abstract that the types of interventions included Tools, Education & Training, Incentives, Modelling and Mentoring, Review & Feedback, Expert involvement, and Policies & Procedures.\nWhilst I was impressed by the Abstract of this article, and the overarching goal, I was unfortunately left disappointed by the full manuscript itself due to a lack of detail, clarity, and interpretation. Most importantly, the article does not outline the 93 interventions identified or refer the reader to a list of these – I was unable to locate a list of the 93 interventions on the author’s OSF page, which shows an example table of only 12 interventions. Furthermore, the Results section does not report these in detail and the Discussion section focuses more on general international/government-level priorities and interventions for open science, whilst the article’s focus was outlined to focus on institutional interventions. It is imperative that you share the full inputs and outputs of this research to aid reader interpretation and reuse of the taxonomy, and to aid transparency and reproducibility of this work, and further detail about these would make this paper a lot more useful and impactful. For example, you could outline the interventions in the Results section using the categories you outline in the Abstract (i.e. Tools, Education & Training etc.).\nFurthermore, I found the description of Methods confusing/inconsistent between the Abstract and the Methods sections; clarification here is key so that the reader fully understands how this taxonomy was developed.\nNevertheless, I do think that this paper has merit so I am hoping that the authors are able to revise it accordingly. I hope my comments are useful to the authors in improving the manuscript.\nMajor comments regarding clarity and accuracy:\nYou state throughout, e.g. third sentence of the Abstract, that this paper is a ‘review’. However, this is not a review in the formal sense (e.g., systematic, narrative etc.). Given that the aim of this paper is to create a taxonomy of interventions, it would be better to consistently phrase it as such.\n\nIntroduction: You state that “Low reproducibility means that original protocol, materials or data sets may not be available to conduct analysis to reproduce the results” but this is not completely true – even when protocols, materials, and datasets are available, there is evidence of low reproducibility due to non-transparent reporting and/or errors. See Obels et al. (2020) where this problem is also demonstrated in registered reports that aim to incorporate these practices [ref 1]. I also disagree with your definition of replicability, “low replicability relates to the inability to re-conduct or re-conduct well an entire study or experiment, regardless of whether the results replicate” – many studies focus on low replicability rates of replication attempts (e.g., the OSC 2015 who estimated a 36% successful replications), so the definition of low replicability does indeed include consideration of ‘whether the results replicate’. I would simply rephrase your definitions of reproducibility and replication to more accurately describe them. I tend to use the definitions provided by the National Academies of Sciences, Engineering, and Medicine, 2019: [ ref 2 ] which is also used nicely in this paper: [ ref 3 ]\n\nIntroduction, “The flow-on effects impact research users such as industry” – in what way does it impact? Can you expand on this seemingly important point?\n\n“Some key stakeholders in improving the research system to improve quality are researchers, journals, and research funders, as well as research institutions” a paper that may help support your point here is: [ ref 4 ]. To clarify, I am a co-author of this paper, but it supports the identical point that you currently make without a reference to support it. The paper is titled “Reforms to improve reproducibility and quality must be coordinated across the research ecosystem” and states “In this commentary, we—the Local Network Leads of the UK Reproducibility Network—outline our response to the UK House of Commons Science and Technology Committee’s inquiry on research integrity and reproducibility. We argue that coordinated change is needed to create (1) a positive research culture, (2) a unified stance on improving research quality, (3) common foundations for open and transparent research practice, and (4) the routinisation of this practice. For each of these areas, we outline the roles that individuals, institutions, funders, publishers, and Government can play in shaping the research ecosystem. Working together, these constituent members must also partner with sectoral and coordinating organisations to produce effective and long-lasting reforms that are fit-for-purpose and future-proof. These efforts will strengthen research quality and create research capable of generating far-reaching applications with a sustained impact on society”. It would be helpful to include a figure of Michie’s behaviour change wheel in the Introduction to guide the reader (if you search “Michie behaviour change wheel” in Google images, you can see lots of different ways that researchers have done this, and I see that you do use a figure in your video abstract, which is great!). Other research teams have applied Michie’s behaviour change wheel to meta-scientific research and these should be cited so as to better situate this paper and not oversell its novelty, e.g. [ ref 5 ] and [ ref 6 ]. To transparently outline, I am a co-author on the 1st recommended article; my recommendation is not based on my co-authorship here, but because we specifically use the COM-B model within the context of open science practices. The paper at current outlines no other work that has used Michie’s behaviour change wheel in meta-scientfic research, but the two references here highlight that work does indeed apply such model and is proving to be very useful in this regard. Inclusion of these references therefore bolsters the point made my the authors. I recommend moving the aim of this ‘review/taxonomy’ upwards so that it comes directly after “What might research institutions do to improve the quality and reproducibility of their research?”… “This review aims to develop a taxonomy of possible interventions to improve research quality…”. I was searching for a specific aim in this paragraph and only got to it at the end. Situating it first will aid reader interpretation.\n\nThe end of the Introduction states “To assist this process, we first aimed to identify and classify published and unpublished examples, including studies that assessed the interventions” but the Abstract states that the first step was to “1) Use an exemplar paper looking at journal-level interventions to improve research quality”. Can you clarify the steps in each of these sections to ensure consistency/accuracy. Furthermore, the Introduction ends after you state “we first aimed to…”, meaning that the reader does not know what happened in the other stages. You could either delete this sentence from the Introduction and use the Method section to accurately outline the steps, or add all steps after this sentence in the Introduction.\n\nI am confused by the Methods section because of the Abstract – the Abstract states that the first step was to “use an exemplar paper looking at journal-level interventions…” but the Methods then suggests that multiple articles were used (“a set of seed articles”). Please clarify the Methods throughout the paper. These seed articles should also be specified and cited here.\n\nResults: Please include the direct URL to the OSF site where the supplementary materials (i.e., the full taxonomy) are held. I was able to find this by searching OSF to guide my review (https://osf.io/gfw72/).\n\nIn Table 1, for the Chauvin (2019) paper, under “Population” it states “ECRs (although at the journal-level, is translatable?” – what do you mean by this? Is the sentence in brackets meant to be there?\n\nDiscussion: You suggest that your taxonomy aligns with both Michie’s behaviour change wheel and the Nosek pyramid. First, it would be helpful to expand what you mean by the ‘Nosek pyramid’ because this not a well-known term. The citation is also to the OSC (2015) paper – is this correct? Second, you may be interested in also mapping your taxonomy to a recent paper that categorises open research initiatives into procedural, community, and structural change [ ref 7 ]. For full transparency, I am a co-author on this paper and we are currently in the process of writing up a systematic literature review of such initiatives. It occurs to me that your taxonomy fits these three thematic categories.\n\nMinor stylistic recommendations:\n[Abstract]: The first two sentences of the Abstract use the word ‘research’ six times – can you rephrase or remove this term so that is doesn’t appear so much? E.g. it can be removed from before ‘reproducibility and replicability’.\n\n[Introduction]: At the term ‘rates’ to the end of this sentence: ”Studies in disciplines as diverse as economics, cancer biology, psychology, machine learning, ecology, and social sciences have found disappointingly low reproducibility and replicability”.\n\n[Methods]: Remove the duplication of the word ‘potential’ in the following sentence: “Because the potential range of potential interventions..”.\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? 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": "311817",
"date": "26 Aug 2024",
"name": "Helen Niemeyer",
"expertise": [
"Reviewer Expertise Open Science",
"Meta-Research",
"Psychology"
],
"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\nThank you for inviting me to review this manuscript on a very important topic. However, I have a number of concerns and would be glad if the authors could address them: There is no reference for Michie’s behaviour change wheel provided until the last page of the manuscript. There could be (in general) more references throughout the introduction and methods section. The paragraph “What might research institutions …” on page 3 is a bit confusing. The order of the sentences seems not follow a clear argumentation. The objectives of the paper are neither described in the introduction nor in the methods section. The taxonomy is presented as given, instead it could be described that the objectives were to develop and evaluate such a taxonomy. On page 3, a sentence in the middle of a paragraph starts with “This review aims (…)” which let´s the reader guess that a review was conducted. It is not introduced that the/ a taxonomy will be developed from findings of the literature review. There are no clear in- and exclusion criteria provided. How was the set of seed articles and reviews identified? In which databases was the forward and backward citations search conducted? Where do I find the information to reproduce stage 1 and 2? Page 3: ” This Stage 1 search identified a key review article on interventions to improve adherence to reporting guidelines for journals, which included a suggested taxonomy. We then drafted an initial taxonomy and used the other interventions identified from the searches to test and modify this proposed intervention taxonomy.” – it is not described based on which criteria the key article was identified/classified as key, and it is not described based on which method or criteria how the initial taxonomy was drafted and how (and which) other interventions were used to test and modify it. Page 4: I have concerns that the taxonomy and review from 2021 and 2022 are still timely, because meta-research and reproducibility are a very active and timely field. The authors may have missed important developments from the last 3 years? Usually (systematic) reviews should be published within 6 months after the end of the literature search in order to be timely. Page 5: If the results of the review, and the taxonomy, are supposed to be applied, how can they be used? Table 1 only provides short notes/headlines, without references? For example: “Create research teams with effective mix of research expertise” – if I want to do that, how does this statement (and the manuscript) help me to concretely do it? What is an effective mix? Without a reference to a text that provides more information for each of the aspects it is impossible to use the information provided in the taxonomy. Can the authors add that? I couldn´t find an overview of the 93 different possible interventions and no list of excluded papers/interventions. Can the authors provide it? In terms of replicability and reproducibility this should be the foundation of their own review. How many raters/authors conducted the literature search, and the “data extraction”? Was this conducted by two raters and was the interrater reliability computed? This is usually a fundamental quality criterion for reviews. Page 8: Why was Michies wheel and not Noseks pyramid chosen? Thank you!\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?\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": []
}
] | 1
|
https://f1000research.com/articles/13-883
|
https://f1000research.com/articles/12-998/v1
|
17 Aug 23
|
{
"type": "Systematic Review",
"title": "An Assessment of Contemporary Methods and Data-Enabled Approaches for Early Cataract Detection",
"authors": [
"Chris Muchibwa",
"Muawya H. Sarnoub Eldaw",
"Mu Mu",
"Michael Opoku Agyeman",
"Muawya H. Sarnoub Eldaw",
"Michael Opoku Agyeman"
],
"abstract": "Background: Cataracts are common causes of visual impairment. Preventing blindness requires an early and accurate diagnosis. This review examines current cataract diagnosis strategies, explores data-driven machine learning algorithms for early detection, investigates the use of artificial intelligence (AI) approaches, assesses improvements in cataract detection accuracy, identifies research gaps, and provides recommendations for future studies. Methods: We gathered labelled cataract and non-cataract fundus data from the Kaggle. Scholarly publications were sourced from reliable databases such as ProQuest, IEEE, ELSEVIER, Google Scholar, and PubMed. A detailed literature search with specific terms expanded the scope of this review. We included studies that used cataract and non-cataract fundus eye images from cross-sectional, retrospective, and prospective studies. The quality assessment used the AMSTAR tool, considering factors such as literature search comprehensiveness, study selection criteria, data extraction methodologies, and study validity (Table 1). Results: This study encompassed 130 research publications, focusing on machine learning models and clinical-based diagnostic approaches for early-stage cataract identification. The performance of machine-learning models is influenced by factors such as dataset noise and limited reliable data. Barriers to the successful implementation of AI for cataract diagnosis were identified. Conclusions: This review emphasises the obstacles hindering the broad application of AI in cataract diagnosis. Addressing these findings is vital for developing strategies to overcome these challenges and enhance cataract detection systems. To achieve improved accuracy and efficiency in cataract diagnosis, future research should prioritise efforts to enhance dataset availability and quality, reduce data noise, and refine machine-learning algorithms. Unlocking the full potential of AI and/or machine learning can lead to significant breakthroughs in cataract diagnosis, ultimately resulting in better patient outcomes and reduced visual impairments.",
"keywords": [
"Cataract",
"Artificial intelligence",
"machine learning",
"deep learning",
"data optimization",
"image pre-processing",
"fundus images",
"slit-lamp images",
"hyperparameter tuning."
],
"content": "Introduction\n\nThis review comprehensively evaluates existing cataract detection strategies by focusing on recent advances in data-driven machine learning (ML) and/or artificial intelligence (AI) methodologies. The purpose of this study was to address the constraints and challenges associated with traditional clinical assessment methods and investigate the feasibility of employing ML and/or AI to automate cataract diagnosis. Furthermore, this review identifies gaps in the current literature and suggests prospective directions for future research on cataract detection.\n\nThe aims and research questions of this review are as follows:\n\n- To evaluate the shortcomings of current cataract detection approaches, particularly those related to early detection and standardisation.\n\n- To investigate the use and advancement of ML and/or AI approaches in cataract diagnosis.\n\n- To identify the difficulties and limitations of merging traditional methodologies with AI in cataract diagnosis, such as the availability of annotated datasets and grading system consensus.\n\n- Propose tactics and future initiatives for enhancing cataract diagnosis, such as extensive dataset collection, uniform grading criteria, and hybrid ML model exploration.\n\nThis review focuses on people with cataracts and underlines the use of machine learning and/or artificial intelligence (AI) approaches in cataract detection and diagnosis. It examines the global prevalence of cataracts, the limitations of traditional diagnostic methods, and the potential benefits of data-driven machine learning and/or artificial intelligence technologies.\n\nA scoping study was conducted to provide a detailed overview of the existing literature on cataract detection. It identifies gaps and limitations in the literature and proposes potential future study topics. This review guarantees that the assessment is based on trustworthy evidence, thus contributing to the improvement of knowledge in cataract diagnosis. This study investigates the possible application of artificial intelligence (AI) techniques for early detection and addresses the limits and constraints of current cataract diagnosis methods. By assessing hurdles and adopting AI in cataract diagnosis, this study aimed to increase the efficiency, accuracy, and accessibility of cataract diagnostic services.\n\n\nMethods\n\nCataracts play a substantial role in the global prevalence of visual impairment.1–3 The identification of ocular diseases at an early stage is critical for preventing vision loss and improving patient outcomes.3,4 Despite the potential of artificial intelligence (AI) in cataract screening, its widespread usage is limited in many healthcare settings, particularly in areas with limited access to eyecare services and economic constraints.2,3,5–7 The use of AI technologies has the potential to increase the chance of an early diagnosis of cataracts,5,6,8,9 reduce undetected instances or features linked to cataracts (e.g., change in retinal veins and artery size and structure, shape of cataract formation on the lens, colour change of the lens disc, uneven corneal surface, leukocoria, or red reflex appearance in the pupil), and allow time for treatment before the cataract is at an irreversible severe stage, thereby improving community health.9–17 Numerous AI approaches have been developed to address the challenges associated with cataracts, such as limited-service availability, mistakes, and misdiagnoses. Both clinical and AI-based techniques have been proposed for computerised cataract diagnosis and treatment. Currently, the most common method for identifying cataracts is through manual eye examinations performed by ophthalmologists, which frequently include slit-lamp examinations, ophthalmoscopes, etc.18–21 However, this strategy has drawbacks owing to variances in physician experience, which result in variable diagnostic outcomes.21–23 The application of human vision as a standard detection technique used by eye specialists has a limited ability to detect tiny changes in lens opacity using different types of image modalities, which may result in missed early-stage cataracts or misdiagnosis of ocular illnesses, particularly those genetically linked to cataracts.5,6,8,22,24–27 However, these limitations prevent effective use of eye screening tools in cataract detection. The availability of correctly labelled, high-quality data is important for the efficient training of AI systems.19,28 To ensure patient trust, ethical factors such as patient privacy, data security, and informed consent must be addressed.29 Building trust in eye care services, whether through clinical examinations or AI-powered solutions, encourages more people to undergo regular eye examinations. Collaboration and coordination among technology specialists, healthcare professionals, and politicians are required for the successful integration of AI into existing eyecare infrastructure.30 A validation method is required to ensure the dependability and authenticity of the AI systems.31 The WEKA tool can be used to determine the effectiveness of AI models in the accurate and early detection of cataracts by assessing different algorithmic models.32–34 The simulation results can aid in the selection of an optimal algorithmic model that accomplishes the intended objectives and provides cutting-edge solutions. Improving the algorithm’s performance entails meticulous adjustments through hyperparameter tuning and careful exploration of the hyperparameter space using approaches such as grid search, random search, and Bayesian optimisation.35,36 Data collection and preparation, designing an appropriate model architecture, separating data for training and validation, optimising hyperparameters, and conducting model training and validation are all critical aspects for developing improved cataract detection models.35,37 These elements are critical for improving the effectiveness of machine-learning models.\n\nPreferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines38,39 were followed in this work. However, it is unfortunate that the study is not currently available online, and there is a lack of registration information, including registration numbers.\n\nAmong the eligible sources of evidence, this review includes numerous crucial characteristics. First, the studies were limited to those published in the previouspast 15 years, allowing us to capture the most recent developments in cataract detection methodologies, such as advances in AI and/or machine learning, while also taking into accountconsidering traditional diagnostic methods. We aimed to investigate the issues associated with early-stage cataract diagnosis and highlight the importance of the data provided by focusing on current publications. Second, in order to be considered, the publications must be written in English. Because English is widely utilised in scientific research, this decision was made to ensure that writers fully comprehend and evaluate the findings, as well as consistency in data extraction and interpretation.\n\nThe inclusion criteria were fully published journal articles to highlight the quality and trustworthiness of the evidence.40 This technique ensured that the review contained only papers that had completed a rigorous evaluation procedure, including peer review. This study examined studies that used fundus and slit-lamp datasets, which are both extensively used in. This technique ensured that the review contained only papers that had completed a rigorous evaluation procedure, including peer review. This study focuses on two types of image modalities, namely slit-lamp and fundus images and slit-lamp, for specific reasons. Slit-lamp images provides high-resolution images of the eye’s anterior segment, enabling detailed examination of the lens and other structures.41–46 It allows the precise localisation and characterisation of different types of cataracts based on their position within the lens. Additionally, the dynamic adjustment of light and slit orientation permits various perspectives and lighting conditions for viewing cataracts in real-time.40,47 In contrast, fundus images indirectly evaluate lens clarity by assessing the appearance of the red reflex.48–50 They enable the examination of not only the lens but also other structures at the back of the eye, aiding in the identification of associated pathologies. Fundus imaging is non-invasive and well tolerated by patients, facilitating easy monitoring. Digital documentation of fundus photos (images) allows for convenient tracking of cataract progression and selecting the appropriate time for surgical intervention.12,13,16,43,51,52 Slit-lamp and fundus imaging are critical for the early detection and evaluation of cataracts. Slit-lamp images are useful in a variety of investigations owing to their ease of use and accessibility.53–59 However, fundus imaging can reveal important information regarding posterior segment involvement and its impact on retinal health.51,60–62 It is critical to recognise that these imaging modalities should be used in conjunction with other diagnostic tools and that a full eye examination performed by a skilled ophthalmologist is still the gold standard in cataract diagnosis.63–67 Furthermore, the incorporation of AI and machine learning algorithms shows promise in terms of increasing cataract detection; however, further study and validation are needed to ensure clinical application and efficacy.34,68–70\n\nIn terms of patient characteristics, there were no age or sex restrictions on the inclusion criteria. It is crucial to note, however, that most studies have concentrated on people aged 50 years and older, potentially overlooking other age groups. This is in contrast to the research direction of this study, in which people of various ages and sexes were deemed eligible for inclusion, ensuring a comprehensive assessment of various cataract diagnostic methodologies across diverse patient populations and advancing our understanding of the subject.\n\nOverall, the inclusion criteria for evidence sources were carefully selected to include recent breakthroughs, be understandable and reliable, and include a wide range of diagnostic procedures and patient characteristics.\n\nThis review used several databases and direct interactions with the authors to acquire a diverse range of credible materials. The databases chosen, including ProQuest, IEEE, Elsevier, and PubMed, are well known for their vast coverage of scientific literature across a wide range of subjects, including cataract research.71 These databases provide access to peer-reviewed journals, conference papers, and scholarly publications, allowing a comprehensive search of relevant materials. Furthermore, email interactions among authors were used to evaluate individual journal articles and identify other sources, thereby boosting the thoroughness of the literature review. To ensure that the review included the most recent studies, the most recent search was undertaken in June and July 2023. The period from 2008 to 2023 was chosen with care to include the most recent research findings on cataracts and related diagnostic tools. This review provides an up-to-date understanding of cataract diagnosis and incorporates the most recent advancements in this field by including recent publications published during this designated period. A thorough and extensive collection of information resources for this literature review was compiled using a combination of database searches and direct communications with the authors. This method ensures that various published works are included and has the ability to unearth pertinent supplemental studies, resulting in a full and reliable review of the issue.\n\nAs part of the search strategy, a complete literature review was conducted using various academic databases. This link will lead you to an example of a PubMed database search strategy: https://pubmed.ncbi.nlm.nih.gov/. Relevant terms were linked in the search box using Boolean operators (AND and OR) to perform a thorough search. The primary purpose of this study was to identify and assess cataract journal articles, specifically techniques of diagnosis or detection, and to investigate the potential applications of artificial intelligence and machine learning. To boost search efficacy, constraints and filters such as specifying a publication date range and language limits were applied. The chosen database(s) was used to conduct the search and collect articles that met the present criteria. The titles and abstracts were evaluated for relevance, and publications that satisfied the qualifying criteria were selected for further research.\n\nThe ability to read the entire text of the selected papers was essential for gaining thorough knowledge of the methodology, findings, and consequences. To maintain the most recent scientific results, the search method must be regularly adjusted. Other databases, such as Scopus, Web of Science, and Embase, were considered in addition to PubMed to locate additional papers. Manual searches of relevant journals, conference proceedings, and reference lists have also been suggested as viable techniques to identify additional sources. In addition, grey literature sources, such as reports, theses, and dissertations, were recognised for their capacity to provide helpful insights and diverse perspectives.\n\nAdapting the search technique to the specific needs of each database and changing the search terms and combinations are key components in providing effective and comprehensive results.\n\nIn this scoping investigation, a two-stage screening and eligibility technique was employed to select the appropriate sources of evidence. First, the papers were assessed by examining their titles and abstracts to determine their relevance to the research topic. This screening technique aided in the identification and removal of articles that were extraneous to or outside the scope of the study. Following the filtering procedure, the remaining articles were thoroughly assessed to determine whether they met the criteria. The admission criteria emphasised research on the application of AI and/or machine learning (ML) techniques in the diagnosis of cataracts. In the investigations, both cataract and non-cataract fundus eye images were preferred. Furthermore, these papers had to be completely available or fully published in English. A total of 130 studies met the inclusion criteria and satisfactorily addressed the review objectives. These studies provide important information on the application of AI and/or ML in cataract diagnosis. Articles that did not meet the inclusion criteria were excluded. Articles that were excluded had not been published in English or were unrelated to machine learning and traditional cataract diagnosis. A total of 270 items were deleted from the final analysis.\n\nThe following suggestions were made to improve the selection process:\n\nConduct a pilot screening phase: A small number of articles should be pilot screened prior to the entire screening operation.72 This simplifies the eligibility conditions while guaranteeing reviewer uniformity. To boost dependability and minimise prejudice, several reviewers should be included in the screening and eligibility process. Each reviewer independently reviewed the papers, and there were group discussions through Microsoft Teams to settle any concerns and reach an agreement.\n\nConsider employing screening software or platforms: Using tools or software platforms such as Scholarcy, Zotero and AMSTAR tool can help organise and manage the screening process more effectively. These technologies help reviewers collaborate and maintain track of the screening process. Clarifying the eligibility and qualifying criteria at the start of the review process is critical for ensuring consistency and openness. This reduces ambiguity and simplifies the selection process. A thorough record of articles rejected during the screening process was kept, as were the explicit reasons for their rejection. This form facilitates reporting and promotes transparency during the review process. The scoping review’s evidence selection method is thorough, transparent, and replicable based on these guidelines.\n\nOne of the objectives of this literature review was to comprehensively investigate the utilisation of artificial intelligence (AI) and machine learning (ML) technologies for the purpose of identifying cataracts. In order to accomplish this objective, an extensive examination of scholarly literature from esteemed sources such as ProQuest, IEEE, Elsevier, and PubMed was undertaken, encompassing a diverse array of scientific topics. The most recent search was conducted on July 3, 2023. The primary objective of our study was to examine the difficulties associated with the implementation of artificial intelligence (AI) in the context of cataract detection, as well as its potential influence on patient outcomes. Furthermore, we provided recommendations for further investigation in this field. The main aim of this study was to conduct a thorough analysis of the potential advantages of artificial intelligence (AI) in the diagnosis of cataracts. The data was systematically organised and presented in a structured format to enhance coherence and clarity during the evaluation phase, thereby facilitating comprehension.\n\nIn order to ascertain the dependability and calibre of nonrandomized research studies incorporated in systematic reviews and meta-analyses pertaining to the early detection or diagnosis of cataracts, we employed the AMSTAR tool along with its methodical evaluation procedure. By utilising the AMSTAR tool comments and published reviews, it is possible to ascertain potential biases and evaluate the quality of the study. The utilisation of an analytical and comparative approach greatly enhances the validity and utility of the findings obtained from our research on cataracts.\n\nIn the assessment of both established clinical and emerging AI diagnostic methodologies, a comprehensive analysis was conducted on a range of imaging modalities, including fundus imaging, slit-lamp imaging, and computed tomography (CT). Among these options, slit lamps are particularly notable for their user-friendly nature and their significant research value, as they possess the capability to capture images utilising conventional cameras. The analysis was conducted using the Murad tool, comprising of eight queries that pertain to selection, verification, causality, and reporting. According to the information provided in Table 1, a rating of five or above was deemed suitable for the evaluation. The aim of the study was to assess and present quantitative data regarding potential strategies for addressing the difficulties associated with the detection of ocular diseases, particularly cataracts. The investigation conducted by researchers involved the examination of different approaches for the identification of cataracts. This was achieved through the utilisation of a classification framework that incorporated two distinct sets of images: one comprising images with cataracts and the other consisting of images without cataracts. The primary objective was to evaluate the precision of cataract detection.\n\nThis review provides an overview of the data-gathering factors considered. One thousand fundus images were obtained from the Joint Shantou International Eye Centre (JSIEC) in Shantou City, Guangdong Province, China as part of an open dataset (see Underlying data for details76). These images were part of a larger collection of 209,494 fundus images that were used for training, validation, and testing. The data source is provided, as well as a link to the Kaggle repository.\n\nThe fundus images in the collection were divided into 39 distinct classes, each of which correlated with a different fundus disease or condition. Each image is classified into one of the classes based on its distinguishing characteristics. Simplifications and assumptions: We assume that the 1000 fundus images chosen for this dataset are representative of a larger collection and include the full range of fundus diseases and disorders prevalent in the general population. The URL of the dataset is provided at the following link: Kaggle repository. Furthermore, we assumed that fundus images were appropriately classified into 39 sickness categories by field specialists. The dataset assumes that the labels assigned to each image are correct. Data validation is essential for ensuring the integrity and reliability of the datasets. We propose an extensive validation and quality assessment of fundus images, as well as class classification. Expert evaluation, inter-rater reliability testing, and a comparison of the dataset to recognised gold-standard diagnoses are all possible. Data augmentation techniques were used to boost the unpredictability and diversity of the dataset. The purpose of this method is to improve the applicability and robustness of deep-learning models trained on this dataset. This section also provides precise definitions and detailed explanations of the 39 classes of fundus diseases and disorders in the dataset. This will aid in comprehension and allow the findings to be applied and interpreted correctly. Ethical considerations are crucial when collecting and utilising fundus images. Patient privacy must be safeguarded by following appropriate ethical standards, obtaining informed consent, and anonymizing individual identifying information. By following these directions and meticulously scrutinising the assumptions and oversimplifications, researchers can effectively use fundus imaging databases and obtain reliable results from their analysis.\n\nThe results synthesis entailed a detailed categorization and review of journal articles gathered from diverse sources, with the goal of discovering noteworthy patterns and subjects pertinent to the research aims. These articles were arranged around fundamental concepts such as cataract diagnosis procedures, algorithm performance requirements, and dataset features.\n\nA data charting technique was used to systematically summarise the information retrieved from the articles. We used tables or charts to present the main findings of each study article accurately, including details such as the accuracy rates achieved by different machine learning algorithms, sample sizes used for training and testing, and significant limitations or challenges encountered during the research process.\n\nFollowing this, the data-charting findings were rigorously scrutinised to uncover the common themes, patterns, and trends seen across several studies. The major goal was to gain a thorough understanding of the effectiveness and limitations of AI and/or ML for cataract diagnosis.\n\nThroughout the synthesis process, great care was taken to ensure the validity and reliability of the findings. Inconsistencies or contradictions were thoroughly evaluated, and efforts were made to reconcile conflicts or provide clarification.\n\nA comprehensive approach was used for article extraction and quality assessment. The AMSTAR tool was used to evaluate the methodological rigour of the systematic reviews, including characteristics such as the depth of the literature search, study selection criteria, data extraction methodologies, and study validity. Author names, publication year, country of origin, research design, sample size, cataract severity, diagnostic procedures used, and difficulties faced in accessing publications were included. The methodological quality of the areas of selection, comparability, and results were thoroughly assessed, resulting in an improvement in the overall quality of the journal selection process.\n\nA logical and rigorous technique was used to manage and condense the journal articles, allowing for the systematic analysis of articles from various sources. This comprehensive methodology allows for a full examination of the available information, resulting in the identification of major insights and recommendations for future research and practise.\n\n\nResults\n\nIdentifying evidence sources is critical in academic research. We performed a thorough search across different databases, resulting in the identification of 400 relevant studies. We refined our selection to 130 studies that matched our inclusion criteria after deleting duplicate data and carefully reviewing titles and abstracts. We have provided a flowchart (Figure 1) that details the criteria used to establish the eligibility of the published journals for inclusion in our research. This was done to guarantee transparency in the selection process. This flowchart provides a quick overview of the essential features of the featured studies. In addition, for reference purposes, we included a compilation of publications that were not included in the full-text analysis in the Extended Data section.\n\nFurthermore, based on our review of the studies, we would like to make recommendations for further research in this area. First, it would be useful to investigate the efficacy of various machine-learning algorithms in cataract detection and compare their performance with established diagnostic approaches. Furthermore, researching the impact of implementing AI and ML technologies on patient outcomes and healthcare efficiency will provide useful insights. Furthermore, large-scale clinical trials to validate small-scale study findings and test the generalisability of AI-based cataract diagnosis would be beneficial. Finally, ethical issues of AI deployment in cataract diagnosis, such as patient privacy and data security, should be investigated. These research directions would help advance the field.\n\nFigure 1 depicts the features of the evidence sources used in the analysis. The majority of the included studies (130) used a cross-sectional design. Notably, we found a high number of recent articles (100), with an emphasis on artificial intelligence (AI) approaches for cataract diagnosis. Furthermore, 30 of these publications focused on the clinical aspects of cataract diagnoses.\n\nWe gathered a dataset of 1000 ocular fundus images with various features to aid in the evaluation of cataract occurrence. These images were taken from the Kaggle dataset and heavily processed to determine the presence or absence of cataracts based on their different features. Each image was annotated for future reference. However, it should be noted that the clarity of the ocular images was insufficient to distinguish the gender of the individuals involved. Furthermore, the participants in the study ranged in age from 40 to 65 years.\n\nBased on these findings, we would like to make suggestions for further research in this area. Investigating the possibility of combining sophisticated imaging techniques, such as high-resolution retinal imaging, could improve the clarity and precision of ocular images for cataract diagnosis, could improve the clarity and precision of ocular images in cataract diagnosis.77–81 Improving ocular image quality and precision for cataract diagnosis is critical for proper therapy. Several technical approaches can be utilised to accomplish this:\n\nThe paragraph examines different technical methodologies aimed at enhancing the clarity and precision of ocular images in the context of cataract diagnosis. High-resolution imaging techniques such as Optical Coherence Tomography (OCT) and Scheimpflug imaging provide accurate cross-sectional images of the eye, facilitating the visualisation of areas affected by cataracts81–86 Adaptive Optics is a technique utilised to mitigate the effects of optical distortions, thereby enhancing the clarity and sharpness of images.87 Contrast enhancement algorithms are utilised to increase the disparities in pixel brightness, thereby facilitating improved discrimination between healthy and cataractous regions.88 The utilisation of Image Registration techniques enables the alignment of multiple eye photographs taken at different time points, thereby facilitating precise tracking of cataract growth. Deep Learning-based Image Analysis employs machine learning algorithms to train models that are capable of detecting and segmenting cataracts in medical images.76,89–93 This approach enables the extraction of quantitative measurements related to the presence and severity of cataracts. Polarimetric imaging is a technique that allows for the identification of unique characteristics of cataractous tissue, thereby improving the ability to distinguish it from healthy tissue.94 The technique of Multimodal Imaging Fusion involves the integration of data obtained from various imaging modalities, resulting in a comprehensive depiction of the anatomical structures of the eye and enhanced diagnostic precision.95 Real-time image processing involves the optimisation of algorithms to provide immediate feedback during the acquisition of images.96 The implementation of standardised imaging protocols facilitates the attainment of consistent and dependable outcomes across various clinics and equipment.81,97 Using these methods will result in more accurate cataract assessments and better patient outcomes. Furthermore, the implementation of longitudinal studies that encompass a broader age spectrum has the potential to generate significant findings regarding the progression and enduring effects of cataracts.98–102 Furthermore, expanding the dataset to include a wider range of individuals from different ethnic backgrounds and geographical locations could potentially improve the applicability of the results to a broader population.103–105 Finally, investigating the association between the occurrence of cataracts and systemic conditions like diabetes or hypertension could provide valuable insights into potential risk factors and coexisting medical conditions.106–108 Engaging in the exploration of these research avenues would contribute to the advancement of our understanding of cataracts and bolster evidence-based practises in diagnosis and treatment.109,110\n\nThe purpose of this evaluation was to evaluate the quality and trustworthiness of individual evidence sources for inclusion in research studies or literature reviews. It should be noted, however, that the scoping review did not include a comprehensive evaluation of each individual source.\n\nSeveral studies have examined the use of machine-learning techniques for cataract diagnosis. When evaluated on a dataset of 2,073 images, Li et al.54 used a convolutional neural network (CNN) on digital slit-lamp images and attained an accuracy rate of 94.1%. With a dataset of 1,410 images, Wang et al.4 used deep learning approaches on optical coherence tomography (OCT) images and attained a precision rate of 91.84%. On a dataset of 500 images, Akram et al.96 used a convolutional neural network on slit-lamp images and achieved a precision rate of 92.5%. Guo et al.91 employed various deep learning models on slit-lamp pictures, with the ResNet50 model attaining 98.4% accuracy on a 1,000-image dataset. Kavitha et al.85 used deep learning techniques on OCT images and achieved 96.7% accuracy with a collection of 500 images. For anterior segment OCT images, Zheng et al.84 proposed utilising a mix of CNN and SVM classifiers. They obtained a 95.7% accuracy rate with a dataset of 1,000 scans. Wang et al.4 created a deep learning method for slit-lamp images, reaching 95.7% precision using a dataset of 1,000 images. Khan et al.40 created a diagnostic system combining CNN and transfer learning, attaining a precision rate of 96.08% on a 1,000-image dataset. Raza et al.57 developed a deep learning system based on transfer learning, attaining a precision rate of 98.6% on a 1,000-image dataset. With a dataset of 200 images, Zarei-Ghanavati et al.58 created an AI system to detect cataracts on slit-lamp images, achieving an accuracy score of 94.1%. With a dataset of 3,456 images, Yoo et al.59 used transfer learning techniques and attained a precision rate of 95.2%. With a dataset of 5,000 images, Liu et al.89 employed CNNs on slit-lamp images and achieved an accuracy rate of 98.9%. With a dataset of 1,000 images, Li et al.54 used a deep learning methodology on slit-lamp images and attained an accuracy rate of 94.1%. On a dataset of 3,200 images, Cheng et al.97 discovered that deep learning methods outperformed traditional machine learning techniques with a precision of 96.8%.\n\nThese studies collectively highlight the potential of machine learning and deep learning techniques in cataract diagnosis, demonstrating promising accuracy rates and performance across various imaging modalities.\n\nTo further advance the field, we suggest conducting comparative studies that directly compare different machine-learning algorithms to identify the most effective approach for cataract diagnosis. Additionally, expanding the dataset to include a more diverse population in terms of age, ethnicity, and geographical distribution would enhance the generalizability of detection systems. Furthermore, it would be valuable to investigate the real-world implementation and clinical feasibility of AI-based cataract diagnosis, considering factors such as workflow integration, user friendliness, and cost-effectiveness. Finally, exploring the ethical considerations associated with the implementation of machine learning algorithms in clinical settings, including patient privacy protection and data security, is of utmost importance. These research directions will contribute to the continued advancement and practical utilisation of AI for cataract diagnosis.\n\nIn the critical appraisal of various researchers or authors of the journal articles included in this review, certain limitations should be acknowledged. These studies have the following limitations:\n\nLimited Sample Size: Several studies, such as Li et al.54 with 8,287 images, Akram et al.96 with 500 images, and Zarei-Ghanavati et al.58 with 200 slit-lamp images, utilised limited datasets. The small sample size restricts the generalizability of the data and its ability to encompass the full range of patients with cataracts. Additionally, the diversity of datasets used in different studies is limited. For instance, some studies have focused exclusively on specific imaging modalities, such as OCT imaging or anterior segment OCT imaging. Notably, these small datasets may not adequately represent the variations and complexities observed in real-world patients with cataracts. Absence of External Validation: Some studies relied solely on the same dataset for training and testing without utilising external datasets for model validation.36 This lack of external validation can lead to an overestimation of the model’s performance and restrict the applicability of the findings. Inadequate Comparative Analysis: While Cheng et al.97 conducted a comparison between deep learning and traditional machine learning algorithms, many publications did not evaluate their proposed approaches against established procedures or alternative algorithms. This limitation hampers the ability to assess the superiority or additional value of the suggested models.111 Furthermore, these studies primarily focused on analysing algorithm performance measures, such as accuracy, precision, and sensitivity, using specific image datasets without providing information on real-world clinical validation or the impact on patient outcomes. Publication bias may have influenced the selection of research for this compilation, potentially limiting the coverage of the entire body of literature on the use of AI and ML approaches for cataract diagnosis.112,113 The exclusion of studies with contradictory or unfavourable findings may have contributed to this bias. It is crucial to consider these limitations when interpreting the findings of individual studies. Further research is warranted to delve deeper into these aspects, which will enhance our understanding and the practical application of AI and/or ML in cataract diagnosis.\n\nTo address these limitations and further advance the field, we recommend conducting studies with larger and more diverse datasets that encompass a broader range of patients with cataracts. Additionally, researchers should emphasise the importance of external validation to assess the generalizability and robustness of the proposed models. Comparative analyses of established procedures and alternative algorithms would provide a clearer understanding of the performance and value of the proposed approaches. Moreover, future studies should incorporate real-world clinical validation and investigate the impact of AI and/or ML on patient outcomes. Finally, efforts should be made to overcome publication bias by including a comprehensive range of studies, regardless of their findings, in order to provide a more balanced view of the field. By addressing these suggestions, we can advance the knowledge and practical implementation of AI and ML in cataract diagnosis.\n\n\nDiscussion\n\nThis review provides a concise summary of the evidence regarding cataract detection and evaluation. Cataracts affect various ocular tissues, including the cornea, iris, pupil, lens, and retina. Recent research has highlighted the impact of cataracts on the lens, leading to changes in visual acuity and the need for eyewear adjustments.27,30,114,115 Eye doctors use corneal topography to detect abnormalities on the corneal surface, which can be indicative of cataracts.116 Other potential diagnostic markers for cataracts include changes in pupil diameter, light sensitivity, colour perception, and lens opacity in the iris.17,117–120 Cataract formation often results in visual symptoms such as reduced contrast sensitivity and increased sensitivity to glare, both of which are influenced by pupil size and responsiveness. Systematic pupillometry has shown promise in monitoring cataract progression and determining the optimal timing of treatments.118,120,121 Ophthalmologists play a crucial role in accurately diagnosing cataracts through a thorough examination of the lens. Techniques such as Scheimpflug and anterior segment optical coherence tomography (OCT) enable precise visualisation of the lens, thereby facilitating the detection of lens opacities.46,82 Optical Coherence Tomography (OCT) is a powerful imaging method that is frequently employed in medical and research settings. However, it has limitations in that researchers should be aware of its use in their research. Depth constraints, poor performance in highly scattering tissues, low lateral resolution, and a narrow field of vision are among these limitations. Artefacts can potentially alter OCT images, making their interpretation difficult.25,122,123 Furthermore, OCT may have poor contrast in particular tissues and might be expensive and difficult to obtain in some research contexts.86 Despite these limitations, OCT is useful for a variety of scientific applications, particularly ophthalmology, dermatology, and cardiology. These limitations can be addressed by researchers through good experimental design, picture processing, and validation using alternative imaging techniques. Understanding the merits and disadvantages of optical coherence tomography (OCT) is critical for making informed judgements in research efforts. Cataract symptoms are commonly observed in the retina, particularly in the macula. Ocular examination and imaging methods help to identify changes in lens clarity, opacity of the lens disc, and associated retinal disorders. Cataracts significantly affect visual function, including acuity, contrast sensitivity, and retinal well-being.121 Components such as the visual field and contrast sensitivity can be utilised to detect cataract-related issues. It is crucial for healthcare providers to have knowledge of various ocular components and their involvement in cataract development, as this aids in early identification, treatment options, and patient education.124 Comprehensive examination of ocular tissues such as the cornea, iris, pupil, lens, and retina is essential for early detection of cataracts and provides valuable insights into their onset, progression, and treatment.48,78,79,118\n\nHowever, diagnostic research on cataracts has certain limitations that must be addressed. Selection bias can occur when datasets do not adequately represent the entire patient population, leading to over- or underrepresentation of specific groups.83 Heterogeneity in the diagnostic criteria, measurement methodologies, and outcome assessments hampers data comparability.83,121 Dataset limitations weaken statistical power and may result in inaccurate or inconclusive results. Larger datasets with greater statistical power are required to assess the efficacy of the diagnostic measures.98,99,125,126 The absence of longitudinal data limits our understanding of cataract development, treatment success, and the predictive value of diagnostic tests.69,127–129 Also, the research results can’t be used with different groups of people because the images used to diagnose cataracts aren’t varied enough. This includes issues with resolution, age, race, and other diseases.117,121 It is crucial to validate the diagnostic algorithms using diverse datasets or real-world clinical settings.34,112 These limitations undermine the reliability, usefulness, and generalizability of research on cataract diagnosis. Overcoming these constraints is vital for improving cataract diagnosis. It is essential to acknowledge and overcome these obstacles when proposing alternative techniques. To address potential selection bias, researchers should ensure that sample datasets represent a larger study population and avoid the disproportionate inclusion of specific subgroups.130 Standardised methods and methodologies enhance the comparability of the data and the reliability of the conclusions drawn from them. Increasing the sample size through multicentre studies and collaborations enhances statistical power, reduces errors, and improves diagnostic precision.90,106\n\nLongitudinal studies that track patients over time are crucial to understanding cataract development, treatment outcomes, and long-term implications. A broad range of research perspectives and external validation are necessary for a comprehensive analysis. Researchers and academic journals should avoid publication bias by disseminating positive and negative results. Implementing pre-registration and transparent reporting practises can reduce publication bias while improving the accuracy and effectiveness of diagnostic procedures. Comparisons with existing diagnostic methods are essential to assessing the efficacy of novel procedures. Evaluating the feasibility, cost efficiency, and patient outcomes is crucial for determining the effectiveness of diagnostic techniques. Longitudinal assessments of diagnostic procedures are required to understand their impact on visual function, therapeutic efficacy, and overall quality of life. By addressing these limitations, researchers can enhance the accuracy and reliability of cataract diagnosis, leading to improved patient outcomes and advancements in this field.\n\nThis study has identified several limitations and challenges associated with cataract detection techniques. While these strategies are promising, they face significant obstacles that hinder their successful implementation. To maximise the benefits of these approaches, it is crucial to recognise and address their limitations. In this section, we explore the key obstacles and constraints affecting the suggested strategies.\n\nOne major obstacle is the scarcity of financial and infrastructure resources, which impedes the widespread use of modern imaging technologies and artificial intelligence (AI) algorithms for cataract detection. In many locations, limited resources and healthcare services create inequality, hindering the adoption of diagnostic technologies. Adequate training and skills among healthcare practitioners are essential for the successful deployment of advanced imaging technologies and AI techniques. However, acquiring proficiency in these technologies requires time and poses challenges in terms of skill acquisition and continued education. Addressing these issues requires significant investment in training and professional development. Despite the potential effectiveness of public awareness campaigns and educational programmes, achieving widespread patient information and participation remains a significant challenge. Linguistic barriers, cultural perceptions, and socioeconomic disparities can hinder patients’ involvement in and adherence to screening initiatives. Overcoming these obstacles is crucial for the success of such endeavours.\n\nEnsuring uniformity in diagnostic criteria and techniques across diverse healthcare settings and geographic locations is challenging. Differences in the application and analysis of diagnostic techniques can compromise the reliability of the results and impede the development of universally accepted standards. To bridge these gaps and advance standardisation, collaboration between healthcare professionals and stakeholders is necessary. The collection and management of sensitive medical data are essential for the adoption of AI technology; however, this raises concerns about confidentiality and data protection. Protecting patient confidentiality and preventing unauthorised access and breaches are critical considerations. Establishing robust data privacy and security measures is a complex process that presents new challenges. Striking the balance between technological adoption and patient privacy requires comprehensive plans and strict adherence to privacy legislation. The implementation of new technology and collaborative care models must align with regulatory frameworks and legal norms, involving obtaining necessary authorization, addressing liability concerns, and adhering to local laws. Complex administrative processes and impediments can result in delays and increased administrative burdens, necessitating coordinated efforts to manage these regulatory difficulties successfully.\n\nIntegrating innovative approaches and technologies into the current healthcare system requires thorough strategic planning and teamwork. This may entail interprofessional collaboration, organisational restructuring, and process changes in healthcare settings. However, it is essential to acknowledge that these proposed changes may face opposition or encounter practical problems, underscoring the significance of effective leadership and active participation from the relevant parties for successful implementation. Extensive scientific validation and compelling data are necessary to determine the efficacy and impact of these activities. Further research is required to assess the effectiveness, cost-effectiveness, and clinical outcomes of these novel approaches. Such investigations require a significant amount of time, resources, focus, and dedication to ensure a comprehensive examination. Despite these limitations, it is crucial to invest in research, collaboration, and resource allocation to overcome these challenges. Infrastructure and educational investments can expedite the detection of early cataracts. By recognising and addressing these limitations, healthcare institutions can strive for higher detection rates, faster therapeutic interventions, and improved visual outcomes in patients with cataracts. The benefits of these efforts outweigh their limitations, highlighting the importance of the continued development of reliable cataract detection devices.\n\nFuture research directions for cataract diagnosis and therapy hold promise for significant progress. Numerous strategies are currently being investigated to enhance the accuracy, reliability, and availability of diagnostic tools and treatments for cataracts. In this discussion, we focus on the following areas:\n\nUnderstanding patient engagement: further research is needed to understand how individuals with varying degrees of cataract actively seek medical assistance. This knowledge is crucial in identifying patients who may delay or underutilize cataract therapy, leading to vision loss or blindness. Exploring the underlying causes of patient reluctance to seek help is vital for increasing awareness, improving diagnostic accuracy, and enhancing treatment accessibility. The implementation of targeted techniques can effectively address this issue and improve cataract diagnosis, treatment, and patient outcome.\n\nIntegration of datasets and modalities: researchers are investigating the integration of diverse datasets and modalities, including wearable technologies such as spectacles and contact lenses, to enhance cataract identification and monitoring. Telemedicine systems and data-driven cataract detection technologies show potential for screening and monitoring patients in remote locations. Further research in these areas can lead to improved efficiency and accessibility for cataract diagnosis and monitoring.\n\nLifestyle factors and novel interventions: more research is necessary to understand the impact of lifestyle factors such as dietary patterns, physical activity levels, smoking behaviours, and UV radiation exposure on the onset and progression of cataracts. Evaluation of the effectiveness of cataract screening and treatment interventions, especially in disadvantaged rural and low-income areas, is crucial. Furthermore, the exploration of alternative approaches, including gene and stem cell therapies, holds promise in the field of cataract treatment.\n\nAdvancements in diagnostic technologies: several noninvasive diagnostic technologies, such as optical coherence tomography (OCT), machine learning algorithms, tear fluid analysis, spectroscopy, Raman spectroscopy, and hyperspectral imaging, have been looked at to see if they could help diagnose and measure the severity of cataracts. These innovative methods have the potential to revolutionise cataract detection and evaluation.\n\nIn conclusion, overcoming the obstacles and limitations in cataract diagnosis and treatment requires significant scholarly research, public outreach, and technological innovation. By exploring these research areas, healthcare practitioners can improve the accuracy, availability, and outcomes of cataract treatment, ultimately enhancing ocular well-being and the overall quality of life for cataract patients. Continued efforts in this direction are crucial for advancing the field of cataract diagnosis and therapy.\n\n\nConclusions\n\nIn conclusion, enhancing cataract diagnosis and improving patient outcomes require overcoming the limitations and challenges discussed earlier. To achieve this goal, the following proposals are proposed:\n\nAdequate financial resources: governments, healthcare organisations, and stakeholders should allocate sufficient financial resources to ensure the availability of modern imaging equipment, AI systems, and the necessary infrastructure for cataract diagnosis. This approach addresses resource constraints and facilitates broader implementation of these solutions. Comprehensive training programs should be developed to equip healthcare practitioners with the skills necessary to effectively use and understand new imaging technology and AI approaches. Ongoing professional development courses are also recommended to keep healthcare staff up to date with the latest advancements in cataract diagnosis. Initiatives for public awareness: educational initiatives and campaigns should be conducted to raise public awareness about the importance of timely cataract detection and regular eye screening. Efforts should be made to overcome linguistic and cultural barriers to ensure that essential information reaches marginalized communities. Collaboration among Stakeholders: Collaboration among researchers, physicians, industry experts, and regulatory agencies is crucial for advancing cataract diagnosis and therapy. Such collaborations can lead to the development of new diagnostic tools, improved risk assessment techniques, and advanced imaging technologies. Environmental factors: The impact of environmental factors, such as UV radiation and climate change, on cataract formation and progression should be investigated. Further research is needed to understand the consequences of climate change on ocular conditions, particularly in areas with hotter climates. Randomized datasets from various environmental settings can provide valuable insights into the severity and prevalence of cataracts in different geographical regions, enabling the development of personalized strategies for identification and management. Immune-related illnesses: more research is required to understand the relationship between immune-related illnesses such as rheumatoid arthritis, lupus, diabetes, and cataract formation. The influence of these factors on cataract progression and the effectiveness of corrective treatments should be investigated. User-friendly offline screening tools: It is crucial to develop user-friendly offline screening tools that can quickly capture ocular images and deliver diagnostic results. Patients, especially those in isolated rural areas with limited access to professional healthcare services, would benefit from these devices. Early detection of cataracts can lead to prompt medical intervention, improved outcomes, and a reduction in the global impact of this condition. Establish universal diagnostic criteria and protocols: consensus-building activities are needed to establish universal diagnostic criteria, protocols, and recommendations for cataract diagnosis. Implementing standardization efforts will minimize discrepancies in operating protocols and enhance the integration of diagnostic methodologies. Protecting patient data privacy and security: robust safeguards should be implemented to protect patient data privacy and security. This includes enacting data privacy legislation and establishing secure systems for data collection, storage, and distribution. Thorough research and validation are necessary to evaluate the effectiveness, cost-effectiveness, and clinical outcomes of novel cataract diagnosis approaches. Reliable data should guide the implementation of these therapies and inform healthcare policy decisions.\n\nBy adhering to these guidelines, healthcare organizations can effectively address the strategic limitations associated with cataract diagnosis. The aim is to increase the rate of early detection, facilitate timely care, and improve visual outcomes for individuals with cataracts.",
"appendix": "Data availability\n\nThe fundus dataset used, which consists of 1000 photos of the fundus, is an open dataset. 76 This dataset can be accessed using the following link: https://www.kaggle.com/datasets/linchundan/fundusimage1000.\n\nAll these 1000 fundus images which belong to 39 classes are come from the Joint Shantou International Eye Centre (JSIEC), Shantou city, Guangdong province, China.\n\nThe dataset is shared under a Database Contents License (DbCL) v1.0.\n\nMendeley: The PRISMA checklist and Evaluation of searched papers of ‘An Assessment of Contemporary Methods and Data-Enabled Approaches for Early Cataract Detection’. https://doi.org/10.17632/y5hs9c24v3.1\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\nAdio A, Nwachukwu H: Comprehensive management of pediatric cataract in Africa. Niger. J. Ophthalmol. 2016; 24(1): 1. 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Publisher Full Text\n\nAumann S, Donner S, Fischer J, et al.: Optical Coherence Tomography (OCT): Principle and Technical Realization. High Resolution Imaging in Microscopy and Ophthalmology. 2019; pp. 59–85. PubMed Abstract | Publisher Full Text\n\nLiu L, Wu Z, Qi M, et al.: Application of Adaptive Optics in Ophthalmology. Photonics. 2022, April 23; 9(5): 288. Publisher Full Text\n\nZhang X, Ren Y, Zhen G, et al.: A color image contrast enhancement method based on improved PSO. PLoS One. 2023, February 9; 18(2): e0274054. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu J, Liu D, Gu J, et al.: A Deep Learning Model for Cataract Grading on Slit-Lamp Images. Front. Med (Lausanne). 2021 Oct 12; 8: 742962. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIdowu P: Model for Prediction of Cataracts Using Supervised Machine Learning Algorithms. Computing, Information Systems, Development Informatics & Allied Research Journal. 2017; 8: 47–62. 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Publisher Full Text\n\nWu H, Chen G, Zhang G, et al.: Application of Multimodal Fusion Technology in Image Analysis of Pretreatment Examination of Patients with Spinal Injury. J. Healthc. Eng. 2022, April 12; 2022: 1–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAkram MU, Khalid S, Tariq A, et al.: Automated detection of cataract from slit-lamp images using a deep learning-based approach. J. Med. Syst. 2019 Nov 6; 43(12): 337. PubMed Abstract | Publisher Full Text\n\nCheng X, Li H, Li L, et al.: Artificial Intelligence for Cataract Diagnosis: A Comparison of Deep Learning and Traditional Machine Learning Methods. J. Healthc. Eng. 2020 Nov 4; 2020: 8888264. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJunayed MS, Islam MB, Sadeghzadeh A, et al.: CataractNet: An Automated Cataract Detection System Using Deep Learning for Fundus Images. IEEE Access. 2021; 9: 128799–128808. Publisher Full Text\n\nWu X, Xu D, Ma T, et al.: Artificial Intelligence Model for Antiinterference Cataract Automatic Diagnosis: A Diagnostic Accuracy Study. Front. Cell Dev. Biol. 2022, July 22; 10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPathak S, Kumar B: A Robust Automated Cataract Detection Algorithm Using Diagnostic Opinion Based Parameter Thresholding for Telemedicine Application. Electronics. 2016, September 15; 5(4): 57. Publisher Full Text\n\nHambisa MT, Dolja-Gore X, Byles JE: A longitudinal analysis of factors associated with age-related cataract among older Australian women: a cohort study of 7851 older Australian women 79–90 years. Ir. J. Med. Sci. 2022, August 17; 192(3): 1525–1536. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlein BEK, Klein R, Lee KE: Incidence of Age-Related Cataract. Arch. Ophthalmol. 1998, February 1; 116(2). Publisher Full Text\n\nGianattasio KZ, Bennett EE, Wei J, et al.: Generalizability of findings from a clinical sample to a community-based sample: A comparison of ADNI and ARIC. Alzheimers Dement. 2021, February; 17(8): 1265–1276. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBafeta A, Dechartres A, Trinquart L, et al.: Impact of single centre status on estimates of intervention effects in trials with continuous outcomes: meta-epidemiological study. BMJ. 2012, February 14; 344(feb14 1): e813–e813. Publisher Full Text\n\nKanakamedala A, Go JA, Wendt S, et al.: Systemic and Ocular Comorbidities of Black, Hispanic, and White Women with Cataracts. J. Women’s Health. 2022, January 1; 31(1): 117–124. PubMed Abstract | Publisher Full Text\n\nHuang CY, Lee JI, Chang CW, et al.: Chronic kidney disease and its association with cataracts–A cross-sectional and longitudinal study. Front. Public Health. 2022, December 7; 10. 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Publisher Full Text\n\nChang VS, Gibbons A, Osigian C: Phacoemulsification in the Setting of Corneal Endotheliopathies: A Review. Int. Ophthalmol. Clin. 2020; 60(3): 71–89. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAo M, Li X, Qiu W, et al.: The impact of age-related cataracts on colour perception, postoperative recovery and related spectra derived from test of hue perception. BMC Ophthalmol. 2019, February 20; 19(1): 56. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKoch DD: Glare and contrast sensitivity testing in cataract patients. J. Cataract. Refract. Surg. 1989, March; 15(2): 158–164. Publisher Full Text\n\nVan den Bruel A, Cleemput I, Aertgeerts B, et al.: The evaluation of diagnostic tests: evidence on technical and diagnostic accuracy, impact on patient outcome and cost-effectiveness is needed. J. Clin. Epidemiol. 2007, November; 60(11): 1116–1122. 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Publisher Full Text\n\nMahesh Kumar SV, Gunasundari R: Computer-Aided Diagnosis of Anterior Segment Eye Abnormalities using Visible Wavelength Image Analysis Based Machine Learning. J. Med. Syst. 2018, June 2; 42(7): 128. PubMed Abstract | Publisher Full Text\n\nFan W, Shen R, Zhang Q, et al.: Principal component analysis based cataract grading and classification. 2015 17th International Conference on E-Health Networking, Application & Services (HealthCom). 2015, October. Publisher Full Text\n\nRan J, Niu K, He Z, et al.: Cataract Detection and Grading Based on Combination of Deep Convolutional Neural Network and Random Forests. 2018 International Conference on Network Infrastructure and Digital Content (IC-NIDC). 2018, August. Publisher Full Text\n\nWeng Z: From Conventional Machine Learning to AutoML. J. Phys. Conf. Ser. 2019, April; 1207: 012015. Publisher Full Text\n\nLu W, Tong Y, Yu Y, et al.: Applications of Artificial Intelligence in Ophthalmology: General Overview. J. Ophthalmol. 2018, November 19; 2018: 1–15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGutierrez L, Lim JS, Foo LL, et al.: Application of artificial intelligence in cataract management: current and future directions. Eye Vis. 2022, January 7; 9(1): 3. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVasileiou K, Barnett J, Thorpe S, et al.: Characterising and justifying sample size sufficiency in interview-based studies: systematic analysis of qualitative health research over a 15-year period. BMC Med. Res. Methodol. 2018, November 21; 18(1): 148. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "275570",
"date": "21 May 2024",
"name": "Abdullah Alamoodi",
"expertise": [
"Reviewer Expertise Computer Sceince",
"AI",
"and ML"
],
"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 systematic review provides a comprehensive overview of the current state of cataract detection methods, with a particular focus on data-driven approaches using machine learning and artificial intelligence (AI). The manuscript is well-structured and clearly written, covering relevant topics and offering valuable insights into the potential and challenges of AI in this field. Strengths: The review covers a wide range of topics, including traditional diagnostic methods, AI-based approaches, dataset considerations, ethical implications, and future research directions. The authors describe their search strategy, inclusion/exclusion criteria, and data analysis methods in sufficient detail, allowing for reproducibility. The review critically examines the limitations of existing research, including concerns about sample size, external validation, and potential publication bias. The authors offer specific and actionable suggestions for future research and implementation of AI in cataract diagnosis, addressing both scientific and practical aspects.\nWeaknesses: While the manuscript states adherence to PRISMA guidelines, there is no mention of protocol registration, which is recommended for systematic reviews. The use of the AMSTAR tool for assessing methodological quality of the included studies is briefly mentioned but lacks detailed information about the assessment criteria and scores for individual studies. The review primarily focuses on accuracy as a performance metric, but it would be beneficial to discuss sensitivity and specificity, which are crucial for evaluating the clinical usefulness of diagnostic models. The manuscript focuses heavily on fundus images as the primary data source, even though the review includes studies using slit-lamp images. A balanced discussion of the strengths and limitations of both modalities is recommended. the paper can include some interesting research in the domain, including, (Esam Noori W, et al., 2023 [Ref 1]) and (Hazim Hammed S, et al., 2023 [Ref 2]).\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\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
|
https://f1000research.com/articles/12-998
|
https://f1000research.com/articles/12-769/v1
|
03 Jul 23
|
{
"type": "Case Report",
"title": "Case Report: Activated B-cell-diffuse large B-cell lymphoma",
"authors": [
"Padmashri Kalmegh",
"Alka Hande",
"Madhuri Gawande",
"Swati Patil",
"Archana Sonone",
"Aayushi Pakhale",
"Alka Hande",
"Madhuri Gawande",
"Swati Patil",
"Archana Sonone",
"Aayushi Pakhale"
],
"abstract": "Lymphomas of the oral and oropharyngeal regions are rather uncommon, and diagnosis can be challenging and confusing due to the multiple histological subgroups. Lymphomas are the third most common type of tumor in the head and neck region and are brought on by the lymphoreticular system. The two forms of lymphoma are Hodgkin's lymphoma and non-Hodgkin’s lymphoma (NHL). Herein, we present a case report of oropharyngeal lymphoma. The female patient reported with a complaint of swelling over the palatal region for two to three months. An ulceroproliferative lesion was evident over the posterior palatal region. We diagnosed reactive lymphadenitis based on an incisional biopsy. To confirm the diagnosis and rule out other conditions, a punch biopsy followed by immunohistochemical studies were done. Features suggestive of activated B-cell-diffuse large B-cell lymphoma were confirmed. Among malignant lymphomas, diffuse large B-cell lymphoma is the most prevalent variety. Much progress has been made in recent years in understanding the molecular pathophysiology of this disease. In this case report, we aim to correlate the clinical presentation, histology features and immunohistochemical significance in order to promote early discovery, diagnosis, and treatment for a better prognosis of the patient.",
"keywords": [
"diffuse large B cell lymphoma",
"immunohistochemistry",
"lymphocytes",
"non-Hodgkin’s lymphoma",
"oral cavity"
],
"content": "Introduction\n\nSamuel Wilks coined the term “Hodgkin’s disease,” which is now known as “Hodgkin lymphoma,” in recognition of the earlier report by Thomas Hodgkin from Guy’s hospital in London.1 Lymphomas are a diverse group of lymphoid malignancies with a range of clinical behaviour patterns and therapeutic responses. The histologic type, clinical variables, and more recently, molecular traits all affect the prognosis.2 In terms of prevalence, lymphomas rank ninth among males and tenth among women worldwide. Lymphomas are the second most prevalent type of cancer in the head and neck region, and they rank third after squamous cell carcinoma and salivary gland cancers in the oral cavity. Even though lymphomas account for 3% to 5% of all reported cases in the head and neck region, they are the most prevalent non-epithelial malignant tumors in the same region.3 Typically, no underlying cause of lymphoma is found in any specific occurrence. Nonetheless, other environmental, viral, and genetic risk factors for lymphoma have been discovered. Certain lymphomas have been linked to a number of infectious agents, including Helicobacter pylori, Borrelia burgdorferi, Chlamydia psittaci, and Campylobacter jejuni.4 We adhere to the CARE reporting guidelines to report this Case report.5\n\n\nCase report\n\nA 63-year-old female, presented to the outdoor patient department of our institution in January 2023, with a complaint of a non-healing ulcer over the posterior palatal region for two to three months. She described no symptoms before two to three months but later observed swelling over the posterolateral region of the soft palate. Initially, it was 2 × 1 cm in size and increased to the current size of 4 × 3 cm approximately. She described difficulty in mastication and swallowing. A change in consistency and quantity of saliva was reported by the patient. No history of trauma was present. Intraorally, a single ulceroproliferative lesion present over the anterior faucial pillar was observed (Figure 1, marked with a red circle). The lesion was oval, reddish pink in color, with ill-defined borders, soft to hard in consistency, nonmobile, and had an irregular surface. Uvula deviated to the left side. Lymph nodes in the left submandibular region were palpable, of size 1 × 2 cm, non-tender, and firm in texture. In December 2022, an incisional biopsy was taken with a histopathological diagnosis of reactive lymphadenitis. This was followed by a punch biopsy (Figure 2) in January 2023, with histopathological features suggestive of a lymphoproliferative lesion. No extraoral extension of the growth was evident.\n\nHaematoxylin and Eosin-stained sections showed predominantly a diffuse infiltrate of large-sized atypical B cell population comprising of scant cytoplasm. The nucleus was double the size of the nucleus of a normal lymphocyte, vesicular chromatin, and prominent nucleoli (Figure 3A, marked with red arrows). Complete effacement of normal lymphoid tissue architecture was present.\n\nImmunohistochemical features with cytokeratin staining were negative, CD45 was strongly positive with an intensity score of 3, proportionate scores of 4 (Figure 3B), and CD20 positive. On the basis of histopathological and immunohistochemical features, the lesion was suggestive of an activated B-cell (ABC) subset of diffuse large B-cell lymphoma (DLBCL).\n\nA contrast-enhanced computerized tomography (CECT) presented evidence of a soft tissue density lesion with few non-enhancing necrotic areas noted in the left tonsillar fossa measuring 2.2 × 2 × 2.7 cm (Figure 4A, marked with a red circle) with the following extensions: a. Anteromedially extending into the oropharynx causing partial obstruction with non-visualization of uvula suggestive of involvement abutting the base of the tongue and vallecula (Figure 4B, marked with a red circle). b. Posteroinferiorly involves the posterior pharyngeal wall. c. Laterally involving the peritonsillar space including the pharygobasillar fascia, styloglossus and stylopharyngeus, and the posterior belly of the digastric.\n\nDLBCL becomes less fatal and may even be cured with combination chemotherapy, which only successfully treats less than 50% of patients. The type of therapy will either be curative, where survival is the goal, or palliative, where the goal is to improve the patient’s quality of life, depending on the patient’s status.4 Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for DLBCL patients. Approximately 60–70% of DLBCL patients who continue this regimen are free of illness.6\n\nIn the present case, chemotherapy (cyclophosphamide, hydroxy doxorubicin, oncovin, and prednisone) was used to treat the patient. The patient continued receiving CHOP chemotherapy, and her overall health is improving. A four-month follow-up showed regression of the swelling. The patient is still on treatment.\n\n\nDiscussion\n\nMalignant lymphomas are a category of neoplasms with variable degrees of malignancy that are derived from the lymphoid tissue’s fundamental cells, the lymphocyte, and histiocytes at any stage of development.7 The classification of lymphomas originating from these normal lymphoid populations is challenging since the physiologic immunological roles of lymphocytes vary depending on lineage and degree of development. NHL and Hodgkin lymphoma (HL) are the two main categories into which lymphomas are frequently categorized. NHLs are a variety of lymphoproliferative malignancies that have a far higher propensity to disseminate to extranodal locations than Hodgkin’s lymphoma.2 NHL, a class of neoplasms, occurs due to the uncontrolled proliferation of B-, T-, or Natural Killer (NK) cells. T-cell or NK cell-derived illnesses account for 10 to 15 percent of all NHL cases.8 DLBCL, which accounts for 30–40% of cases in various parts of the world, is the most common NHL. It is most commonly seen in the sixth to seventh decade of life.9 DLBCL is a diverse entity in terms of clinical presentation, genetic advances, therapeutic options, and prognosis. There was a significant advancement when gene expression profiling (GEP) was applied to further detect this variety and provide a rationale for categorizing patients in the study of DLBCL. DLBCL patients are divided into subtypes named germinal center B-cell-like (GCB), ABC, and 10–15% remain unclassified. The ABC subtype is derived from B cells that are undergoing plasma cell development. Patients with the ABC subtype often have the worst prognosis than those with the GCB subtype.10 However, there is morphological and clinical heterogeneity in DLBCL. However, patients with GCB DLBCL still do considerably better than those with ABC DLBCL.11 Expression of CD20 (cluster of differentiation antigens) in lymphoma cells is essential for both making an accurate diagnosis and creating a strategy for biological therapeutic therapy. CD20 antigen is expressed on the surface of neoplastic cells in the majority of B-cell lymphomas, albeit the degree of CD20 expression varies depending on the type of lymphoma and the degree of lymphoma B-cell differentiation. Hence, it is assumed that CD20 expression is high in DLBCL and hairy cell leukemia cells, and low in B-cell chronic lymphocytic leukemia (CLL).12 Particularly, ABC DLBCLs express X-box binding protein-1 (XBP-1), a significant modulator of the secretory phenotype of plasma cells.13 About 25% of ABC DLBCL samples taken from patients have BLIMP1-inactivating mutations in the PRDM1 gene.14 By inhibiting the expression of the majority of mature B-cell differentiation genes, BLIMP1 promotes plasmacytic differentiation.15 Consistent activation of the nuclear factor-kappa B (NF-κB) signaling pathway, which stimulates cell survival and proliferation while inhibiting apoptosis, is another pathogenic characteristic of ABC DLBCLs.16 In order to ensure the most effective use of investigational treatments or currently accessible, frequently expensive therapeutic agents, pathologists must also evaluate the markers required to support their usage. Additionally, pathologists must prioritize sufficient and viable tumor tissue for high-throughput molecular analysis.17–21\n\nAccording to the location and histologic type, clinical presentation differs substantially. Biopsy in conjunction with immunological investigations of biopsy tissue is the only accurate way to identify and classify these lesions.22 No single antibody has been useful for subdividing DLBCL or determining prognosis, according to research by Meyer et al. Because of this, many antibody combinations or methods have been created.23 For the differential diagnosis of 40 cases of oral NHL, Van der Waal et al. used the following antibodies: L26 (CD20, a pan B-cell marker), CD 79a (the immunoglobulin anchoring molecule, so a B-cell marker), CD3, and UCHL 1 (CD45RO), both pan T-cell markers, BerH2 (CD30), and Mib1 (staining primarily B cells).24 Forty cases of oral cavity NHL were studied by Kemp et al. for sex, age, location, clinical presentation, and WHO histological subtype. They found that 98% of the lymphomas in their investigation had a B cell lineage, and the majority of these were histologically subtyped as diffuse large B cell lymphomas (58%). Our study is in accordance with Kemp et al., who used an immunohistochemical panel that included CD3, CD5, CD20, CD45RO, CD79a, leukocyte common antigen, Bcl-2, CD10 and CD23 to validate the lineage and help characterize the subtype. According to them, molecular testing is typically useful in determining genetic infiltration and seems to be a useful supplement to diagnosis.25 In nonimmunocompromised patients, diffuse large B-cell lymphoma in the head and neck region was the most prevalent form observed, according to Hicks and Flaitz, 2001.26 Hashimoto and Kurihara (1982), reviewed pathological characteristics of oral NHL and according to his nine cases and review of the literature, he concluded that B-cell lymphoma is the most common histotype in oral NHL.27 Therefore, in order to diagnose a rare condition, this case report emphasizes the value of early biopsies of oral lesions and the use of a definitive marker among other available immunohistochemical markers.\n\nThe study has limitations due to the patient’s ongoing treatment and the relatively short follow-up time.\n\n\nConclusions\n\nOral NHL is a very uncommon disorder that may cause localized swelling, inflammation, or discomfort in the vestibule, gingiva, or posterior hard palate. DLBCL is a genetically heterogeneous disease with equally different clinical manifestations. Hence, one can determine the malignant nature and prognosis of various kinds of lymphomas by correlating the histological characteristics of these entities. Pathologists should evaluate immunophenotypic and genetic markers that are useful for determining prognosis. In order for the patient to receive therapy at an early stage and have a favorable prognosis, a thorough evaluation of the patient and appropriate investigations are needed for a precise diagnosis.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and clinical images was obtained from the patient.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nZenodo: CARE checklist for ‘Case Report: Activated B-cell-diffuse large B-cell lymphoma’, https://www.doi.org.10.5281/zenodo.7918599. 5\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 acknowledge the support of laboratory technicians from The Department of Oral & Maxillofacial Pathology and Microbiology, Sharad Pawar Dental College & Hospital, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha.\n\n\nReferences\n\nWang HW, Balakrishna JP, Pittaluga S, et al.: Diagnosis of Hodgkin lymphoma in the modern era. Br. J. Haematol. 2019 Jan; 184(1): 45–59. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJiang M, Bennani NN, Feldman AL: Lymphoma classification update: T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms. Expert. Rev. Hematol. 2017 Mar 4; 10(3): 239–249. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Arruda JAA , Schuch LF, Conte Neto N, et al.: Oral and oropharyngeal lymphomas: A multi-institutional collaborative study. J. Oral Pathol. Med. 2021 Jul 1; 50(6): 603–612. PubMed Abstract | Publisher Full Text\n\nMugnaini EN, Ghosh N: Lymphoma. Prim. Care. 2016 Dec 1; 43(4): 661–675. Publisher Full Text\n\nPadmashri K, Hande A, Gawande M, et al.: Activated B-cell-Diffuse Large B-Cell Lymphoma: A Case Report. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nCao X, Ye Q, Orlowski RZ, et al.: Waldenström macroglobulinemia with extramedullary involvement at initial diagnosis portends a poorer prognosis. J. Hematol. Oncol. 2015 Dec; 8: 1–1. Publisher Full Text\n\nSingh R, Shaik S, Negi BS, et al.: Non-Hodgkin’s lymphoma: a review. J. Fam. Med. Prim. Care. 2020 Apr; 9(4): 1834–1840. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHans CP, Weisenburger DD, Greiner TC, et al.: Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004 Jan 1; 103(1): 275–282. PubMed Abstract | Publisher Full Text\n\nPizzi M, Gazzola A, Mannu C, et al.: The role of molecular biology in the diagnosis of lymphoid neoplasms. Front. Biosci. Landmark. 2014 Jun 1; 19(7): 1088–1104. Publisher Full Text\n\nLi S, Young KH, Medeiros LJ: Diffuse large B-cell lymphoma. Pathology. 2018 Jan 1; 50(1): 74–87. Publisher Full Text\n\nFrick M, Dörken B, Lenz G: The molecular biology of diffuse large B-cell lymphoma. Ther. Adv. Hematol. 2011 Dec; 2(6): 369–379. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPrevodnik VK, Lavrenčak J, Horvat M, et al.: The predictive significance of CD20 expression in B-cell lymphomas. Diagn. Pathol. 2011 Dec; 6: 1–6. Publisher Full Text\n\nShaffer AL, Shapiro-Shelef M, Iwakoshi NN, et al.: XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity. 2004 Jul 1; 21(1): 81–93. PubMed Abstract | Publisher Full Text\n\nPasqualucci L, Compagno M, Houldsworth J, et al.: Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J. Exp. Med. 2006 Feb 20; 203(2): 311–317. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShaffer AL, Lin KI, Kuo TC, et al.: Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity. 2002 Jul 1; 17(1): 51–62. PubMed Abstract | Publisher Full Text\n\nDavis RE, Brown KD, Siebenlist U, et al.: Constitutive nuclear factor κB activity is required for survival of activated B cell–like diffuse large B cell lymphoma cells. J. Exp. Med. 2001 Dec 17; 194(12): 1861–1874. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAgarwal P, Chaudhary M, Patil S, et al.: Diagnostic accuracy of various methods to detect lymph node metastasis in oral squamous cell carcinoma. J. Evolution Med. Dent. Sci. 2014 Jun 2; 3(22): 6003–6010. Publisher Full Text\n\nSonone A, Patil S, Hande A, et al.: Correlation of p53 Immunoexpression with Depth of Tumor in Microinvasive Oral Squamous Cell Carcinoma. J. Pharm. Res. Int. 2021; 98–103. Publisher Full Text\n\nKadashetti V, Chaudhary M, Patil S, et al.: Analysis of various risk factors affecting potentially malignant disorders and oral cancer patients of Central India. J. Cancer Res. Ther. 2015 Apr 1; 11(2): 280–286. PubMed Abstract | Publisher Full Text\n\nGupta R, Chaudhary M, Patil S, et al.: Expression of p63 in tooth germ, dentigerous cyst and ameloblastoma. J. Oral Maxillofac. Pathol. 2019 Jan; 23(1): 43–48. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPatil SK: Correlation of Histopathological Metastatic Invasive Prognosticators with Five Years Survival of Oral Squamous Cell Carcinoma. J. Pharm. Res. Int. 2021 Sep 13; 326–333. Publisher Full Text\n\nPicard A, Cardinne C, Denoux Y, et al.: Extranodal lymphoma of the head and neck: a 67-case series. Eur. Ann. Otorhinolaryngol. Head Neck Dis. 2015 Apr 1; 132(2): 71–75. PubMed Abstract | Publisher Full Text\n\nMeyer PN, Fu K, Greiner TC, et al.: Immunohistochemical methods for predicting cell of origin and survival in patints with diffuse large B-cell lymphoma treated with rituximab. J. Clin. Oncol. 2011 Jan 1; 29(2): 200–207. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVan der Waal RI, Huijgens PC, Van der Valk P, et al.: Characteristics of 40 primary extranodal non-Hodgkin lymphomas of the oral cavity in perspective of the new WHO classification and the International Prognostic Index. Int. J. Oral Maxillofac. Surg. 2005 Jun 1; 34(4): 391–395. PubMed Abstract | Publisher Full Text\n\nKemp S, Gallagher G, Kabani S, et al.: Oral non-Hodgkin’s lymphoma: review of the literature and World Health Organization classification with reference to 40 cases. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2008 Feb 1; 105(2): 194–201. Publisher Full Text\n\nHicks MJ, Flaitz CM: External root resorption of a primary molar:“incidental” histopathologic finding of clinical significance. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2001 Jul 1; 92(1): 4–8. Publisher Full Text\n\nHashimoto N, Kurihara K: Pathological characteristics of oral lymphomas. J. Oral Pathol. Med. 1982 May; 11(3): 214–227. Publisher Full Text"
}
|
[
{
"id": "183654",
"date": "17 Jul 2023",
"name": "Junn-Liang Chang",
"expertise": [
"Reviewer Expertise Cancer",
"Pathology",
"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\nReviewer’s comments to Author:\nIs there any laboratory test data that can be presented in this case report? Such as EBV or Serology detection?\n\nDoes the patient have enlarged lymph nodes on other imaging?\n\nPhysical examination for lymph node lesions in other parts?\n\nWhat should be included in the imaging differential diagnosis and clinical differential diagnosis? Can it be determined that he has primary lymphoma?\n\nIs there detection of EBV-related staining or molecular detection in pathological diagnosis?\n\nWhat are the learning objectives of this case report?\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? No\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": "10613",
"date": "29 Nov 2023",
"name": "Padmashri Kalmegh",
"role": "Author Response",
"response": "Respond to the reviewer's comment - 1. No other laboratory test data is presented in the case report. 2. Yes, a few sub-centimetric to centimetric enlarged lymph nodes in bilateral submandibular, jugulo-digastric regions are seen. 3. Physical examination for lymph nodes at other sites including submental, submandibular, supraclavicular, and upper jugulodigastric regions was done. 4. Clinical differential diagnosis may include- Squamous cell carcinoma, Round cell tumor, Reactive lymphadenitis, Pleomorphic adenoma etc. Radiographic differential diagnosis may include - Oropharyngeal squamous cell carcinoma 5. No EBV-related staining was done. For molecular detection of EBV - immunohistochemistry CD45 and CD20 was done as mentioned before. 6. Learning objectives includes - There are many histological subtypes of lymphoma; therefore to differentiate and specify this presented rare subtype, case report would be useful."
},
{
"c_id": "11940",
"date": "03 Jul 2024",
"name": "Padmashri Kalmegh",
"role": "Author Response",
"response": "Comment 1 – Other laboratory investigations that were performed include a complete hemogram, hormonal profile, and immunohistochemistry. Comment 2 - Lymph nodes in the left submandibular region were palpable, of size 1 × 2 cm, non-tender, and firm in texture. Comment 3 & 4– Radiological differential diagnosis may include benign hyperplasia, salivary gland tumor, lymphadenopathy, and nasopharyngeal carcinoma. Comment 5 - there were no EBV-related alterations seen on pathological examinations Comment 6 – The presented case is rare and in this case report we have mentioned its clinical features, aetiology, histopathological features, and various IHC markers in detail that may be the addition to the knowledge of the reader."
}
]
},
{
"id": "288731",
"date": "28 Jun 2024",
"name": "Soundarya Ravi",
"expertise": [
"Reviewer Expertise Hematopathology",
"Leukemia",
"Lymphoma",
"Myeloproliferative neoplasms",
"Flow cytometry"
],
"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 case report discusses about rare presentation of an extranodal DLBCL in the oral cavity in an elderly female presenting with a palatal mass. There are many issues that needs to be addressed in this manuscript.\n1. Abstract: The age of the patient is not mentioned in the abstract.\n\n2. In both the abstract and case report, the authors have failed to mention the site of biopsy. Was it the palatal mass or the left submandibular lymph nodes? If I assume that the biopsy was taken from the palatal mass, then why was it reported as reactive lymphadenitis? Whether any IHC was performed in the initial biopsy? Could you add images of the initial biopsy? Was the initial biopsy not representative of the lymphoma? Kindly clarify in detail.\n3. Introduction: The first line mentioning the history of Hodgkin lymphoma seems redundant in this context. Similarly, the last line also mentions adherence to CARE reporting guidelines, which I feel is unnecessary.\n4. Case report: It would be better if the radiological findings were explained before describing the histopathology. Being written from a pathologist's perspective, I feel the histopathological description, morphological differential diagnosis were not described elaborately when compared to the radiology. In the morphology. how can a pathologist say \"atypical B cell population\". It should be mentioned only after IHC findings.\n5. IHC: What IHC panel was performed for this patient? There was only mention of CD45 and CD20. On what basis, you were able to diagnose it as Activated B-cell subtype? Please clarify. Add corresponding IHC images also.\n\n6. Treatment: The first paragraph is from the literature and should be included in the description and not in the case report.\n7. Discussion: The discussion elaborates on the types of lymphoma, CD20 expression in other lymphomas and molecular subtypes of DLBCL, which could be cut down. It would be better if the authors could discuss about the morphological differential diagnosis of DLBCL in this site and how to exclude them. They can also include a paragraph of the role of IHC in making accurate diagnosis and IHC approach for oral cavity undifferentiated tumors.\n\n8. Nowhere in the article, I could find the incidence of lymphoma in oral cavity and what are the various lymphomas that could present with oral cavity lesion.\n9. Histopathology images: High-power images are required with better clarity to appreciate the morphology. If there was a focus which shows lymphoma and overlying skin ulceration, it would be better representative.\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? No\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": [
{
"c_id": "11939",
"date": "03 Jul 2024",
"name": "Padmashri Kalmegh",
"role": "Author Response",
"response": "The corrections are as follows, In the abstract age of the patient is added. In the abstract and case report site of the biopsy has been mentioned. The first line from the introduction is removed. Radiological findings are updated before histopathological findings. Removed the word ‘atypical’ from the histopathological findings. Morphological differential diagnosis is updated in the discussion section. 1st paragraph from the treatment is added to the discussion. Incidence of lymphoma in the oral cavity is added. Histopathological and CD45 IHC images are replaced. The role of the IHC marker in the diagnosis of NHL is added. Clarifications Comment 2 – Although the site of the biopsy was from the palatal region, on microscopy it showed numerous atypical cells with pleomorphic features. Hence the diagnosis of reactive lymphadenitis was made. IHC was not performed for the initial biopsy. The initial biopsy was taken from OPD so we could not take photographs for the same. Comment 3 – The last line of the introduction is added as per the guidelines of the journal."
}
]
}
] | 1
|
https://f1000research.com/articles/12-769
|
https://f1000research.com/articles/13-874/v1
|
02 Aug 24
|
{
"type": "Case Report",
"title": "Case Report: Cystic artery peptic erosion: Uncommon cause of massive upper gastrointestinal bleeding.",
"authors": [
"Med Dheker Touati",
"Wassim Dziri",
"Rahma Yousfi",
"Nadhem Khlifi",
"Sana Landolsi",
"Faouzi Chebbi",
"Wassim Dziri",
"Rahma Yousfi",
"Nadhem Khlifi",
"Sana Landolsi",
"Faouzi Chebbi"
],
"abstract": "Introduction and importance The cholecystoenteric fistula, a rare complication of cholelithiasis, usually occurs as an internal biliary fistula. Our case features a cholecystoduodenal fistula presenting with severe upper gastrointestinal bleeding originating from the cystic artery. Symptoms vary, and preoperative diagnosis is uncommon.\n\nCase presentation A 63-year-old diabetic patient, who had undergone surgical treatment for a left forearm fracture, presented with persistent bleeding, hematemesis, and melena. Diagnostic esophagogastroduodenoscopy revealed an actively bleeding ulcer on the duodenal bulb, with an attempted hemostasis. Initial stabilization was achieved, but a recurrence occurred after 17 hours with hemodynamic instability. Emergency laparotomy revealed cholecystitis with a cholecystoduodenal fistula, necessitating cholecystectomy and ulcer resection. The source of bleeding was the cystic artery. The patient had a positive postoperative outcome with no recurrence of hemorrhage.\n\nClinical discussion Cholecystoenteric fistulas, forming from obstructed cystic duct inflammation, are rare complications of biliary lithiasis. Most cases are spontaneous, linked to gallstones. Severe upper gastrointestinal bleeding from cholecystoduodenal fistulas is uncommon, often requiring surgical intervention due to cystic artery erosion. Despite advancements in laparoscopic methods, open operations are preferred for anatomical distortion and inflammation. A clear diagnosis involves hepatic angiography and may necessitate embolization. The rarity of this condition emphasizes the need for vigilant diagnosis, especially in patients with gallstone history.\n\nConclusion Massive bleeding from cystic artery erosion by duodenal ulcer through cholecystoduodenal fistula underscores the need for clinicians’ vigilance. Recognition of gallstone disease history is crucial for timely diagnosis in this rare cause of gastrointestinal bleeding.",
"keywords": [
"Cholecystoduodenal fistula",
"Gastrointestinal bleeding",
"Cystic artery",
"Gallstone disease",
"Peptic ulcer"
],
"content": "Introduction\n\nThe cholecystoenteric fistula, an abnormal communication between the gallbladder and the gastrointestinal tract, represents a rare complication of cholelithiasis. The symptoms of cholecystoenteric fistula vary, and an accurate diagnosis before surgery is rarely established. It also rarely presents as upper gastrointestinal bleeding.\n\nIn this context, we present a rare case of cholecystoduodenal fistula that manifested as hypovolemic shock due to massive upper gastrointestinal bleeding, and the origin was identified as the cystic artery. Furthermore, this case reflects the necessary multidisciplinary approach to address the complexity of this condition. This work has been reported in line with the SCARE 2023 criteria.1\n\n\nCase presentation\n\nThis is a case report of a 63-year-old diabetic patient on metformin (850 mg daily) with a history of a left forearm fracture that required surgical intervention, including postoperative intramedullary nailing. The patient received postoperative pain management with non-steroidal anti-inflammatory drugs (550 mg once daily) and a proton pump inhibitor (20mg once daily). He presented to our emergency department with hematemesis persisting for two days prior to admission, along with melena, and no fever. On examination, the patient was hemodynamically unstable with a blood pressure of 70/50 mmHg, a heart rate of 95 bpm, and was afebrile. Rectal examination revealed melena. Laboratory findings showed blood type A+, hemoglobin of 6.5 g/dL, and a prothrombin time of 80%. Renal function was within normal limits.\n\nThe patient was admitted to the intensive care unit with two peripheral intravenous lines, a urinary catheter, normal saline infusion, and a bolus of omeprazole (80 mg), followed by continuous infusion at a rate of 2 mg/hour. Additionally, he received a transfusion of 2 units of packed red blood cells. After stabilization of the hemodynamic status without the need for catecholamines, a diagnostic esophagogastroduodenoscopy was performed, revealing a large ulcer at the anterior wall of the first part of duodenum with active bleeding, classified as Forrest Ib (Figure 1). Adrenaline (1/1000 dilution) was injected for chemical hemostasis, and two clips were applied to achieve hemostasis.\n\nThe patient remained stable for 17 hours but subsequently experienced a recurrence of hematemesis and developed tachycardia and hypotension (blood pressure 80/50 mmHg) with a hemoglobin level of 6.1 g/dL.Catecholamines were initiated, and the patient was taken to the operating room for an exploratory laparotomy. A midline incision revealed features of cholecystitis, with the gallbladder neck adherent to the anterior aspect of the duodenal bulb (Figure 2).\n\nThe release of the gallbladder from the duodenal bulb revealed the presence of an approximately 1cm ulcer with a visible vessel (Figures 3, 4). Cholecystectomy was performed along with en bloc resection of the ulcer and gallbladder. The source of bleeding was identified as the cystic artery (Figure 5). The procedure concluded with pyloroplasty and truncal vagotomy.\n\nCatheterization of the cystic artery (yellow arrow) through a venous catheter across the ulcer (white arrow).\n\nThe evolution was favorable with no recurrence of hemorrhage, along with stabilization of hemodynamic status and hemoglobin levels. The patient was discharged on postoperative day 10. Postoperative follow-up was favorable with no recurrence of hemorrhage after 1 year of follow-up.\n\n\nDiscussion\n\nWe present an exceptionally rare case of gastrointestinal bleeding manifested as hematemesis, related to the erosion of the cystic artery caused by a cholecysto-duodenal fistula and an ulcer on the anterior aspect of the bulb. The study is limited by the patient’s postoperative demise, preventing subsequent follow-up.\n\nCholecystoenteric fistula is a rare complication of biliary lithiasis, with autopsy-reported incidences ranging from 0.1% to 0.5%, and an occurrence of 1.2% to 5% among cases undergoing cholecystectomy.2 This complication is more prevalent in women, typically around the age of 60,2 and the cholecystoduodenal type is the most frequently observed, followed by cholecystocolonic and cholecystogastric fistulas.3\n\nCholecystoenteric fistulas form when the obstructed cystic duct undergoes repetitive inflammation, leading to the adherence of the gallbladder to an adjacent organ.4,5 Approximately 91% to 94% of internally formed biliary fistulas occur spontaneously due to the presence of stones in the biliary tract, with gastric ulcers ranking as the second most common cause. Other potential causes include tumors, biliary abscesses, and echinococcus cysts.6 Most patients present with general features of gallstone disease, but less commonly, patients may also exhibit cholangitis, severe upper gastrointestinal bleeding, or gallstone ileus.\n\nThe cholecystoduodenal fistula is rarely associated with gastrointestinal bleeding. Invasion of the cystic artery by a duodenal ulcer can lead to massive bleeding, while a gallstone can cause erosion of the same artery.2 Severe gastrointestinal bleeding from a cholecystoduodenal fistula is uncommon, as reported by Park et al., who conducted a literature review and identified only 11 case reports.7 Gallstones were the primary cause, with gastric ulcers as the etiology in only two cases. Endoscopic findings varied, ranging from ulcers to fistulous openings and bleeding of unknown origin. Although endoscopic hemostasis was attempted in four cases, surgical intervention was necessary in all cases, consistent with our case report.\n\nThe rarity of this condition, despite the high incidence of cholecystitis, could be explained by the more frequent occurrence of cystic artery thrombosis due to nearby inflammation.8\n\nBleeding from the biliary tract typically occurs into the duodenum, leading to hematemesis and/or melena in patients.9 In cases of upper gastrointestinal bleeding with inconclusive endoscopy results, consideration should be given to a cholecystoduodenal fistula with a bleeding marginal ulcer.9 In a hemodynamically stable patient, a CT scan is required to establish the diagnosis.\n\nEndoscopic ultrasound can detect clots in the cystic duct and the gallbladder lumen, indicating potential bleeding from the gallbladder. A definitive diagnosis is often achieved through selective hepatic angiography, which can reveal a pseudoaneurysm or active bleeding from a nondilated cystic artery. This diagnostic method is particularly valuable because it allows for subsequent selective embolization.10\n\nAngioembolization serves as an alternative treatment in some centers for identifying and potentially stopping active bleeding from a fistula that cannot be managed with endoscopic hemostasis. If angioembolization is performed, it should be followed promptly by surgical intervention.11 This is essential as the clinical presentation of bleeding caused by gallstones might indicate a more complex gallbladder condition than initially suspected.12\n\nCholecystoduodenal fistula leading to severe upper gastrointestinal bleeding is exceedingly rare.9 Most case reports indicate that the bleeding source is typically the erosion of the cystic artery, either by a duodenal ulcer or gallstones. Managing bleeding cholecystoduodenal fistulas usually requires surgical resection of the fistula and repair of the duodenal perforation due to significant bleeding from the cystic artery, which is unlikely to be resolved by conservative methods. In our case, despite the use of diluted adrenaline injections and the placement of hemostatic clips, the patient continued to experience active bleeding.6\n\nWhile laparoscopic methods are often employed due to advanced surgical techniques, open operations are preferred in cases involving anatomical distortion and severe inflammation.\n\n\nConclusion\n\nWe present a unique case of massive bleeding from the cystic artery eroded by a duodenal ulcer through a concurrent cholecystoduodenal fistula.\n\nGiven the rarity of cholecystoduodenal fistula as a cause of massive gastrointestinal bleeding, it is imperative for clinicians to be attentive to certain signs that can facilitate the differential diagnosis. A thorough consideration of medical history remains essential, as a history of gallstone disease can guide the diagnosis.\n\n\nEthical approval\n\nEthical approval for case reports is not necessary.\n\n\nConsent\n\nWritten informed consent to publish this case and associated images was obtained from the patient.\n\n\nAuthor contributions\n\nWassim dziri: Conceptualization, Writing – Original Draft Preparation\n\nMed Dheker TOUATI: Writing – Original Draft Preparation\n\nNadhem khlifi: Writing – Original Draft Preparation\n\nRahma yousfi: Conceptualization, Writing – Original Draft Preparation\n\nSana Landolsi: Conceptualization, Writing – Review & Editing\n\nFaouzi CHEBBI: Supervision, Writing – Review & Editing",
"appendix": "Data availability statement\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nSohrabi C, Mathew G, Maria N, et al.: The SCARE 2023 guideline: updating consensus Surgical CAse REport (SCARE) guidelines. Int. J. Surg. 1 mai 2023; 109(5): 1136–1140. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee SB, Ryu KH, Ryu JK, et al.: Acute acalculous cholecystitis associated with cholecystoduodenal fistula and duodenal bleeding. A case report. Korean J. Intern. Med. juin 2003; 18(2): 109–114. PubMed Abstract | Publisher Full Text | Free Full Text\n\nInal M, Oguz M, Aksungur E, et al.: Biliary-enteric fistulas: report of five cases and review of the literature. Eur. Radiol. 1999; 9(6): 1145–1151. PubMed Abstract\n\nGlaysher MA, Cruttenden-Wood D, Szentpali K: A rare cause of upper gastrointestinal haemorrhage: Ruptured cystic artery pseudoaneurysm with concurrent cholecystojejunal fistula. Int. J. Surg. Case Rep. 1 janv 2014; 5(1): 1–4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChadha M, Ahuja C: Visceral Artery Aneurysms: Diagnosis and Percutaneous Management. Semin. Intervent. Radiol. sept 2009; 26(03): 196–206. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVadioaloo DK, Loo GH, Leow VM, et al.: Massive upper gastrointestinal bleeding: a rare complication of cholecystoduodenal fistula. BMJ Case Rep. 1 mai 2019; 12(5): e228654. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPark JM, Kang CD, Kim JH, et al.: Cholecystoduodenal fistula presenting with upper gastrointestinal bleeding: A case report. World J. Clin. Cases. 16 janv 2021; 9(2): 410–415. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWu TC, Liu TJ, Ho YJ: Pseudoaneurysm of the cystic artery with upper gastrointestinal hemorrhage. Case report. Acta Chir. Scand. févr 1988; 154(2): 151–152. PubMed Abstract\n\nVyacheslav Bard YF: An Unusual Presentation of Cholecystoduodenal Fistula: Massive Upper Gastrointestinal Bleeding. J. Gastrointest. Dig. Syst. 2014 [cité 4 févr 2024]; 05(04). Publisher Full Text Reference Source\n\nContini S, Uccelli M, Sassatelli R, et al.: Gallbladder ulcer eroding the cystic artery: a rare cause of hemobilia. Am. J. Surg. août 2009; 198(2): e17–e19. PubMed Abstract | Publisher Full Text\n\nDelgadillo X, Berney T, de Perrot M , et al.: Successful Treatment of a Pseudoaneurysm of the Cystic Artery with Microcoil Embolization. J. Vasc. Interv. Radiol. 1 juin 1999; 10(6): 789–792. PubMed Abstract | Publisher Full Text\n\nBen-Ishay O, Farraj M, Shmulevsky P, et al.: Gallbladder ulcer erosion into the cystic artery: a rare cause ofupper gastro-intestinal bleeding Case report. World J. Emerg. Surg. 12 mars 2010; 5(1): 8. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "315848",
"date": "11 Sep 2024",
"name": "Odeghe Emuobor",
"expertise": [
"Reviewer Expertise Gastroenterology and Hepatology."
],
"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 describes a rare but important cause of upper gastrointestinal bleeding.\nPlease, the authors will do well to clarify the following: 1. The names of the NSAID and PPI given postoperatively; only the doses are mentioned.\n2. At what point did the patient pass away? While the authors mention that there was no recurrence of bleeding at 1 year of follow up, they also mention the patient's demise as a limitation.\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? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-874
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https://f1000research.com/articles/13-871/v1
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02 Aug 24
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{
"type": "Research Article",
"title": "Effectiveness of Motivational Interviewing and cross platform messaging application in improving oral health knowledge, attitude and behaviours among pregnant women- A Randomized Controlled Trial",
"authors": [
"Amitha Basheer N",
"Praveen Jodalli",
"Inderjit Murugendrappa Gowdar",
"Sultan Abdulrahman Almalki",
"Amitha Basheer N",
"Inderjit Murugendrappa Gowdar",
"Sultan Abdulrahman Almalki"
],
"abstract": "Background Body goes through significant hormonal and physiological changes during pregnancy, which could be linked to changes in oral health. Many women are unaware of the negative consequences of poor dental health during and after pregnancy, both for themselves and their children. Therefore, this study aimed to assess the effectiveness of Motivational Interviewing (MI) and cross platform messaging application (WhatsApp messenger) for oral health education on the oral health knowledge, attitude and behaviours among pregnant women attending ante natal care.\n\nMethods A randomized controlled trial was conducted among 84 pregnant women. Simple random sampling was employed to select participants after oral examination. Participants were randomly allocated to two groups (Group 1: Cross-platform messaging application [WhatsApp]; Group 2: MI) using a lottery method. Pregnant women aged 18 years and older, gestational age between 8 and 30 weeks were included. A face-to-face interview and oral examination were conducted to assess baseline knowledge and oral hygiene status. A follow-up examination was conducted after one month of intervention. Inferential statistics, including the chi-square test and independent t-test, were used to compare variables between the two groups.\n\nResults The mean knowledge score at baseline was comparable between Group 1 (WhatsApp) and Group 2 (MI). However, post-intervention, Group 2 showed a significantly higher mean knowledge score compared to Group 1. Post-intervention, Group 2 exhibited a significantly better oral hygiene status compared to Group 1. Significant improvements in oral health behaviours were observed in Group 2 compared to Group 1 (p < 0.001).\n\nConclusions The findings suggested that while both interventions were effective, MI showed superior results in improving knowledge, oral hygiene status, and oral health behaviours. The personalized and client-centred approach of MI enables participants to explore and resolve ambivalence, promoting a deeper understanding of the importance of oral health during pregnancy.\nRegistration: CTRI (CTRI/2021/09/036407, 10/09/2021).",
"keywords": [
"Pregnancy",
"Oral health",
"Wellbeing",
"Motivational Interviewing",
"Health education",
"Randomized controlled trial",
"Maternal and child health"
],
"content": "Contributions of the literature\n\n\n\n• Current study provided a comprehensive overview on Motivational Interviewing (MI) and its application in healthcare contexts, particularly in promoting behaviour change among pregnant women.\n\n• Study identified the gaps in the current understanding of oral health knowledge, attitudes, and behaviours among pregnant women, as well as the impact of MI and cross-platform messaging applications in promoting health behaviours.\n\n\nBackground\n\nPregnancy induces significant alterations in women’s physical, hormonal, and emotional well-being, profoundly impacting their overall quality of life.1 The body undergoes substantial hormonal and physiological transformations during pregnancy, potentially influencing oral health.2 Pregnancy-associated periodontal diseases emerge as significant changes, manifesting through signs like bleeding, redness, and swelling in the gums.3 When dental calculus and plaque are present, changes in endogenous hormones trigger immune and circulatory responses that amplify the inflammatory response.4 Additionally, the physical and emotional demands placed on pregnant women may contribute to lapses in oral hygiene routines, leading to various complications.5 Prioritizing oral hygiene can play a crucial role in preventing or mitigating the impact of hormone-mediated inflammatory changes in the oral cavity.2\n\nGum bleeding or nausea during the first trimester of pregnancy might cause some women to stop practicing oral hygiene, including brushing their teeth.5 Moreover, over half of pregnant women refrain from visiting the dentist during their pregnancy.6 Suboptimal dental health during pregnancy poses risks for both maternal and foetal well-being, underscoring its significance in prenatal care.7 Improving the dental health of expecting mothers is a proactive measure that should be taken to prevent early childhood cavities.\n\nProviding health education can exert a substantial impact on the health behaviours of individuals and communities, influencing both their living and working conditions.8 The selection and application of proper teaching strategies is critical to the success of health education programmes. Traditional health promotion tactics often focus on giving knowledge and providing recommendations.8 Despite the fact that evidence has shown that conventional health education techniques help certain populations achieve significant improvements in knowledge, attitude, and behaviour, new strategies such as motivational interviewing (MI) have showed promise in helping people adopt better habits. MI has been found to be helpful in areas such as dental health, substance misuse, diet, and exercise as a client-centred technique of enhancing motivation for change by finding and removing barriers to change.6\n\nMany areas of human behaviour and communication have changed dramatically as a result of advances in information technology.9 These shifts have had a significant impact on educational methods. Cross-platform messaging apps keep you connected even if you’re at your desk or on the road, and cloud-synchronized chat logs, contact lists, and settings are essential features.10 With more than two billion active users across 180 nations, WhatsApp is a free standalone instant messaging application (IMA). This was launched in 2009. WhatsApp uses a storable message, allowing health-related information to be given to specific persons, guiding medicine and behaviour, and boosting self-health management.11\n\nWomen lack awareness regarding the adverse outcomes associated with inadequate dental health during and after pregnancy, impacting both their well-being and that of their children. Even though getting orthodontic treatment during pregnancy is safe, many pregnant women choose not to receive it, leading to enduring oral health issues. A proactive strategy could involve educating expecting moms about their oral health and the possible effects of untreated dental caries and gingivitis on the developing baby in order to provide preventive remedies.12 There is a notable gap in existing research, as there is a scarcity of studies examining the effectiveness of educational interventions that incorporate Motivational Interviewing and cross-platform messaging applications such as WhatsApp messenger to improve oral health knowledge and behaviours among pregnant women. Consequently, this study aims to fill this void by assessing the impact of Motivational Interviewing and the use of WhatsApp messenger as tools for oral health education. The primary purpose was to assess the impact of these interventions on the oral health behaviours, attitudes, and knowledge of pregnant women attending antenatal care.\n\n\nMethods\n\nTrial registration: Trial was prospectively registered in Clinical Trial Registry of India with reference number CTRI/2021/09/036407 on 10/09/2021.\n\nA single centred parallel randomized controlled study was carried out at a tertiary care hospital’s Department of Obstetrics and Gynaecology at Yenepoya Medical College Hospital, Yenepoya Deemed to be University, an institute of higher education located in Mangalore, Karnataka, India. 84 pregnant women aged 18 and above, who attended the hospital for prenatal treatment and had gestational ages ranging from 8 to 30 weeks, participated in this randomised controlled trial. Data for the study were collected between February 1st and April 30th, 2022. Before initiating the study, official permission was obtained from the Head of the Department of Department of Obstetrics and Gynaecology at Yenepoya Medical College Hospital, Yenepoya Deemed to be University.\n\nWith an effect size of 0.575 derived from a pooled standard deviation of 5.2 as reported in a significant article by Bahri et al.,12 the sample size of the research was determined using the G*Power software with a 5% level of significance and 80% power. The total sample size for each group was 38. The final total sample size was modified to 84, with 42 participants in each group, to account for a 10% non-response error rate.\n\nParticipants were selected using simple random sampling. Following oral examinations, eligible participants were randomly allocated to two groups using the lottery method. The total sample comprised two groups: Group 1 utilized a cross-platform messaging application (WhatsApp messenger), while Group 2 underwent Motivational Interviewing for oral health education. The enrolment of participants is depicted through the CONSORT diagram (Figure 1).\n\nThe random allocation sequence was implemented using sequentially numbered containers. Steps were taken to conceal the sequence until interventions were assigned by ensuring that the containers were opaque and sealed. This process helped maintain the integrity of the randomization process and prevented any potential bias in the assignment of interventions until the participants were allocated to their respective groups. Statistician with expertise in research methodology generated the random allocation sequence but not directly involved in participant enrolment or intervention assignment to maintain the randomness and reduce bias. Research assistant performed participant enrolment. Research assistant explained the study, obtained informed consent, and ensured that participants meet the inclusion criteria. The assignment of participants to intervention groups was carried out by research coordinator (research guide) who was blinded to participant characteristics to ensure unbiased allocation.\n\nThis study was done in accordance with the principles outlined in the Declaration of Helsinki. Before initiating the study, official permission was obtained from the Head of the Department of Department of Obstetrics and Gynaecology at Yenepoya Medical College Hospital, Yenepoya Deemed to be University. The protocol was reviewed and approved by institutional ethics committee (Yenepoya Ethics Committee-2 of Yenepoya (Deemed to be University), Mangalore, India on 26/02/2021 with reference number YEC2/636. Written informed consent was obtained from eligible participants prior to the study.13\n\nThe study included participants who met the following criteria: confirmed pregnancies, aged 18 years and older, with a gestational age between 8 and 30 weeks, and those who provided informed consent.13 Additionally, participants needed to possess a smartphone at the time of allotment and be familiar with the usage of WhatsApp. The minimum educational qualification required was completion of schooling up to the 7th standard, with the ability to read and write in English, Kannada, or Malayalam.\n\nExclusion criteria comprised individuals with a history of smoking and alcohol consumption. Women with conditions like COVID-19 that could make dental examinations difficult were also excluded from being permitted to participate in the study.\n\nExaminer training and calibration\n\nThe principal investigator underwent training for Motivational Interviewing from MITC (Motivational Interviewing Training and Consulting), accredited with the American Psychological Association and the New Mexico Counselling and Therapy Practice Board. The format for the interview questionnaire was derived from a study carried out by Bansal et al, (2019).14 Questions were modified and validated by two subject experts. The survey questions were designed to evaluate knowledge, attitude, and behaviours and oral health-seeking behaviour among pregnant women, and the accurate responses to these questions and were provided.13\n\nBaseline examination\n\nData collection involved face-to-face interviews and subsequent oral examinations. The one-on-one interviews were conducted in a designated room where participants comfortably sat on chairs. The primary investigator performed interviews to assess pregnant women’s knowledge, attitudes, and practices related to oral health care. Oral examinations were conducted under natural light, supplemented by torch lights when necessary, and performed by a single examiner with the assistance of an assistant. The OHI-S index15 has been used to evaluate the status of oral hygiene, while The Loe and Silness Gingival Index16 was employed to measure gingival inflammation. Contact information, including WhatsApp numbers, was collected from all participants.\n\nUsing both English and their respective regional languages (Kannada/Malayalam), participants in Group I received WhatsApp messages with information on oral health care for expectant mothers and children.\n\nIn Group II, participants received a 20-minute talk based on the Motivational Interviewing (MI) approach, delivered by a dentist trained in MI, who also served as the Principal Investigator (PI). The MI approach encompassed four key aspects: Partnership, Acceptance, Compassion, and Evocation. The motivational interviewing process unfolded in two phases. During the first phase, efforts were made to establish rapport, build trust, and identify the problem of concern. The MI provider established rapport by posing open-ended questions concerning participants’ dental health, their child’s oral health, and their aspirations for both. These were questions that addressed several topics, including establishing commitment to change, seeing potential challenges, strengthening commitment to change, and finding challenges to change.\n\nIn the second phase, the approach shifted from contemplation to the action stage. Participants were asked to consider the benefits and drawbacks of change, along with potential barriers to action for each proposed change. The focus primarily revolved around collaboratively developing an action plan. The principal investigator effectively communicated with patients using the OARS method, which involves Open-ended questions, Affirmations, Reflective listening, and Summarizing.\n\nOpen-ended questions were employed to initiate a conversation between the PI and the patient, encouraging the patient to share thoughts and concerns. Affirmations acknowledged the challenges of behaviour change while highlighting the patient’s strengths to boost self-efficacy. Reflective listening involved actively understanding and comprehending the patient’s statements, fostering a collaborative exploration of behavioural change and motivation. Summarizing demonstrated attentive listening and provided a concise recapitulation of the conversation, aiding in addressing ambivalence.\n\nDuring the one-month follow-up visit after the intervention, the PI conducted interviews with the participants to re-evaluate their knowledge, attitude, and behavior regarding oral health care, employing the same set of questions used during the baseline examination. The OHI-S index and Gingival Index were once again employed for oral health assessments.\n\nDuring the study period, 5 participants were lost to follow-up, with 2 participants from Group 1 and 3 participants from Group 2 failing to complete the follow-up process. Consequently, the final sample size considered for analysis comprised 79 participants, with 40 participants in Group 1 and 39 participants in Group 2.\n\nBy evaluating the effectiveness of the two different therapies, the primary outcome of the study was to improve participants’ knowledge, attitudes, and behaviours related to oral health. A questionnaire was employed for this purpose. Enhancing the participants’ oral health status was the study’s secondary outcome, which was evaluated using the Gingival and OHI-S indices.\n\nData recorded in MS-Excel underwent statistical analysis using SPSS version 24.0.13 While frequency and percentage were used to represent categorical variables, mean and standard deviation were used to express continuous variables. Descriptive statistics, including categorical data, were presented as frequency with percentage in brackets and a 95% confidence interval (CI). Fischer exact test/Chi-square test assessed associations between study variables.\n\nFor comparisons across groups, the Mann-Whitney U Test was employed, and for comparisons within groups, the Wilcoxon signed-rank test was utilised to assess the pre- and post-intervention measures. The Paired t test evaluated the mean change in knowledge scores within each group before and after the intervention, and the Independent Sample T test was used to compare mean knowledge scores between groups before and after the intervention. P<0.05 was set as a statistically significant.\n\n\nResults\n\nThe mean age of participants in Group 1 was 25.28 years, while in Group 2, it was 24.26 years, as shown in Table 1. The majority of study participants in both groups had a Pre-University Course (PUC) qualification, with percentages of 32.2% in Group 1 and 41% in Group 2. Additionally, a predominant proportion of participants identified with the Muslim religion, comprising 49.4% of the overall study population. Regarding the gestational period, a majority of participants (62.0%) were in the second trimester (Table 2). Responses for question 6 and 7 between the groups were included to analyse the attitude of participants towards the oral health. There is no significance (p>0.05) found between the groups for both questions.\n\n* p<0.05 was considered statistically significant. Abbreviations used: NS-non significant p>0.05.\n\nTable 3 presents the comparison of Index scores between the two groups. Before the intervention, the scores for the Debris Index-S and Gingival Index were compared between Group 1 and Group 2, revealing statistically significant differences with p-values of 0.03 and 0.04, respectively. Group 1’s mean debris score was 2.38, while Group 2’s mean score was 2.03. These differences in mean debris scores were statistically significant. Group 2 had a mean score of 2.05. Group 1 had a mean score of 2.33, and the mean gingival score varied significantly between the groups. However, post-intervention scores for the Debris Index-S, Calculus Index-S, OHI-S, and Gingival Index did not show statistical significance (p>0.05).\n\n* p<0.05 was considered statistically significant. P>0.05 Non Significant, NS.\n\nThe comparison of the two groups’ (n=79) knowledge scores is shown in Table 4. Prior to the intervention, there was no statistically significant difference (p>0.05) in the knowledge scores of the participants in the two groups. However, when comparing knowledge scores between the two groups after the intervention, a statistically significant difference emerged with a p-value of 0.006. The mean value for the score after the intervention was 11.08 for Group 1 and 14.08 for Group 2. Furthermore, the change in scores before and after the intervention between the two groups demonstrated statistical significance with a p value of 0.04.\n\n* p<0.05 was considered as statistically significant. p>0.05. Non-Significant, NS. Abbreviations used: df- degree of freedom, SD-standard deviation.\n\n\nDiscussion\n\nPregnancy constitutes a unique physiological state marked by transient adaptive alterations in body structure driven by elevated production of reproductive hormones such as oestrogen, progesterone, gonadotropins, and relaxin. These hormonal effects extend to the oral cavity, resulting in both temporary and irreversible changes, along with pathological modifications.17 Improving dental health in expectant mothers is not only beneficial to their general health but also essential to the oral health of their unborn child. Pregnancy serves as a “teachable time” for women motivated to alter behaviours linked to adverse pregnancy outcomes. The prenatal care team plays a crucial role in encouraging women to adopt good dental hygiene practices, seek oral health expertise, and complete necessary treatments during pregnancy. Integrating oral health treatment into prenatal care is essential for all pregnant women.18\n\nMotivational Interviewing emerges as a significant therapeutic approach with diverse applications in healthcare settings, emphasizing collaborative therapy engagement and respecting the patient’s autonomy.19 Motivational Interviewing aims to empower patients by fostering their self-awareness regarding the need for change and encouraging a voluntary expression of willingness to change. The approach emphasizes autonomy, allowing individuals to arrive at their decisions to change without being directed or coerced by a health practitioner.20\n\nIn recent years, there has been growing attention towards the widespread utilization of modern technology, including cell phones and the internet. Cell phone-based health interventions, particularly those utilizing cross-platform communications, have proven effective for medical and public health purposes. WhatsApp stands out among health education intervention apps due to its ability to provide users with more social information compared to traditional SMS text messaging21–23\n\nThis study examined into the effects of sociodemographic characteristics on pregnant women’s knowledge, attitudes, and behaviours related to oral health. Age, level of education, and religion, however, did not show statistically significant differences in oral health knowledge, attitude, behaviour, or oral hygiene. Conversely, El-Mahdi Ibrahim et al.24 found a strong correlation between age and dental health as well as attitude towards oral health. They also found that there was a strong correlation between education and oral health habits and oral health knowledge. Similarly, Avula et al.25 found statistically significant results regarding the educational qualifications of subjects. Women in different trimesters did not show significant variations in knowledge, which is in line with research by Pentapati et al.26 Furthermore, research by Mart nez-Beneyto et al.27 and Bamanikar et al.28 found a correlation between pregnant women’s educational attainment and dental health.\n\nUnderstanding pregnant women’s oral health knowledge is essential considering the growing global burden of oral diseases. Their depth of knowledge has a direct impact on the oral health care they provide their children as the primary carers. Furthermore, mothers’ active involvement is crucial in influencing their children’s oral health behaviours, which has long-term benefits. In the current study, pregnant women, who make up a significant fraction of the sample, were found to have overall inadequate oral health awareness, indicating that there is a need to improve their understanding. According to a recent study, pregnant women have very little awareness about dental health. Among the participants only 15.2% were aware about the reason for gum disease was due to poor oral hygiene. It might be because, during their routine check-ups, most of them did not receive advice about the significance of dental health during pregnancy from an oral health team or a gynaecologist. The majority of the study subjects (53.2%) exhibited unawareness of other oral hygiene aids, which contrasts with findings from a study by George et al.,29 where it was reported that 83% of respondents used other oral hygiene aids. This study indicates a knowledge gap among participants on the association between impaired oral health and unfavourable pregnancy outcomes, as well as the interconnected connection between pregnancy and oral health. This result is consistent with studies by Avula et al.,25 and Gupta et al.30 Therefore, intensified education efforts are essential to enhance knowledge and alleviate suffering in this regard.\n\nIn a study conducted on the Indian population, parents’ attitudes toward child dental health were reported to be unfavourable, accompanied by poor dental awareness and knowledge.30 Notably, participants who underwent Motivational Interviewing demonstrated enhanced knowledge across a broader spectrum of knowledge items compared to those who received oral health education through WhatsApp messages. This can be due to WhatsApp is flooded with random messages from relatives/friends and people have a common tendency to ignore lengthy messages. Mothers are usually conceived of as the caretakers for their children’s oral health, and the oral health outcomes of early childhood are influenced by their knowledge, beliefs, attitudes, and behaviour related to oral health.\n\nOral health education strategies targeting the enhancement of parental oral health knowledge have demonstrated effectiveness in improving pregnant women’s knowledge, attitudes, and behaviours. However, Motivational Interviewing has been shown to be particularly successful in this regard.\n\nIn addition, the results of this study showed certain general trends that are noteworthy even though they are not statistically significant. The first was a general lack of knowledge, attitude, and practice about oral health issues for children, including the ideal times to introduce a child to the dentist, start brushing their teeth, and bottle feed them at night.\n\nThe data showed that just 17.7% of the participating women had seen a dentist during the previous six to twelve months, with dental pain or issues pertaining to the teeth, gums, or mouth being their primary reason of consultation. None of the participants sought dental care for routine check-ups, and the majority (30.4%) never went to the dentist. This pattern is consistent with research conducted in the United States, which found that even in circumstances in which oral health issues were present, fewer than fifty per cent of pregnant women visited a dentist.31 The literature has identified several reasons why pregnant women may choose not to seek dental care, which includes lack of time, unsatisfactory dental care, negative attitudes towards dental care providers, negative relationships with spouses, and perceptions of dental experiences.32\n\n31.6% of participants in the current study exhibited poor oral hygiene, compared to the 55.7% who showed fair oral hygiene. In a study by Gupta et al.,33 comparable outcomes have been observed. All participants had their Oral Hygiene Index-Simplified evaluated, and the results showed that 15.3% had good oral hygiene, 40.7% had fair oral hygiene, and 44.0% had poor oral hygiene.\n\nA different study conducted in Belgaum, India, by Kashetty et al.34 discovered that the pregnant group had a significantly higher mean OHI-S status (2.68). The current study found that prior to the intervention, a greater percentage of pregnant women (55.7%) had poor oral hygiene. This indicates a considerable level of oral hygiene neglect. Pregnancy-related gingivitis may also intensify discomfort while brushing and regular dental care, which could accelerate the build-up of debris and calculus.35 Oral hygiene status of the participants improved after the intervention. 46.8% of the participants showed fair debris score after the intervention. Calculus score didn’t show much improvement after the intervention since the time of the study was only one month. This time is not enough for change in calculus score. 55.7% of the participants had fair oral hygiene score after the intervention.\n\nBefore the intervention, a higher proportion of pregnant women experienced a moderate form of gingivitis, and 31.6% of the participants had severe gingivitis. After the intervention, the percentage of participants with severe gingivitis decreased, with only 12.5% in Group 1 and 8.9% in Group 2 exhibiting severe gingivitis.\n\nIn a study conducted by Kashetty et al.34 in Belgaum city, Karnataka, a higher proportion of pregnant women (66.6%) suffered from severe gingivitis. The presence of pregnancy gingivitis might contribute to increased difficulty in brushing and regular dental care, potentially accelerating the deposition of local irritants like debris and calculus.36 The intervention in your study appears to have contributed to a reduction in the severity of gingivitis among the participants.\n\nConsidering this was the first study of its kind in the Indian population to evaluate women’s level of understanding regarding oral health as well as their attitudes and behaviours concerning dental health, the study’s strength is its novelty.\n\nThe study also investigates the impact of two distinct oral health education methods (Motivational Interviewing and Cross-platform messaging using WhatsApp) on women’s knowledge acquisition and improvement in oral health and hygiene.\n\nHowever, the study has limitations. It relies on self-reported data, introducing potential biases inherent in this method, such as misclassification of the questions being asked. Additionally, most women completed the face-to-face questionnaire within a short time frame (5 to 10 minutes), and questions pertained to the last year, posing a risk of recall bias. Chance of social desirability bias was present since the method of data collection was face to face interview, it might cause might result in under reporting also. Study duration was too less to assess the change in Calculus index score and OHI-S score. There is a common tendency to ignore lengthy WhatsApp messages, so it might have affected the knowledge score after intervention. The study acknowledges certain limitations, particularly in terms of the sample size. It suggests that a longitudinal study involving a larger number of participants would be desirable to provide more robust and comprehensive findings.\n\n\nConclusion\n\nMaintaining good dental health throughout pregnancy is beneficial for the expecting mother’s health as well as the well-being of the unborn child. Despite these possible advantages, the current study shows that pregnant women lack knowledge and awareness about oral health, with a significant percentage unaware of the consequences of continuing poor dental hygiene during pregnancy. It is necessary to recognise pregnancy as a “teachable” phase, offering a chance to encourage women to take up healthy practices. To promote improved oral health outcomes for the mother and the new-born, it is essential that women as well as their families receive guidance emphasising the importance of dental care during pregnancy.\n\nBoth educational interventions in this study resulted in improved scores, with participants who received Motivational Interviewing showing a significant increase in oral health knowledge, along with positive changes in attitude, behaviour, oral hygiene, and oral health status post-intervention. Thus, it is critical to employ a variety of health promotion strategies throughout pregnancy to motivate and inform pregnant mothers about the significance of maintaining optimal dental health. Furthermore, integating discussions about oral health into obstetric care can potentially enhance patients’ awareness and prompt them to schedule dental visits. The demand for innovative, consistent, and comprehensive public health communication strategies aimed at reaching women and promoting oral health in a timely and accessible manner is evident.\n\n\nEthics and consent\n\nThis study was done in accordance with the principles outlined in the Declaration of Helsinki. Before initiating the study, official permission was obtained from the relevant authorities.\n\nThe protocol was reviewed and approved by institutional ethics committee (Yenepoya Ethics Committee-2 of Yenepoya (Deemed to be University), Mangalore, India on 26/02/2021 with reference number YEC2/636. Written informed consent was obtained from eligible participants prior to the study.13\n\nConsent of publication: Not applicable\n\n\nAuthors’ contributions\n\nABN: Conception of the work, data acquisition, interpretation of data, drafted the work\n\nPJ: Conception of the work, data analysis, revised the draft, supervision",
"appendix": "Data availability\n\nFigshare: Effectiveness of Motivational Interviewing and cross platform messaging application in improving oral health knowledge, attitude and behaviours among pregnant women- a Randomized Controlled Trial. https://doi.org/10.6084/m9.figshare.25116926. 13\n\nThis project contains the following data:\n\n- EXCEL SHEET.xlsx (underlying data)\n\n- Additional file 2 CONSORT-2010-Checklist.doc (CONSORT checklist)\n\n- INFORMED CONSENT FORM.docx\n\n- QUESTIONNAIRE AND CORRECT ANSWERS.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\nFaculty, Department of Public Health Dentistry, Yenepoya Dental College, Mangalore, India.\n\nHead of the Department, Department of Obstetrics and Gynaecology, Yenepoya Medical College and Hospital, Mangalore, India.\n\n\nReferences\n\nEstebsari F, Kandi ZRK, Bahabadi FJ, et al.: Health-related quality of life and related factors among pregnant women. J. Educ. Health Promot. 2020 Nov 26; 9: 299. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHemalatha VT, Manigandan T, Sarumathi T, et al.: Dental considerations in pregnancy-a critical review on the oral care. J. Clin. Diagn. Res. 2013 May; 7(5): 948–953. Epub 2013 Mar 21. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWu M, Chen SW, Jiang SY: Relationship between Gingival Inflammation and Pregnancy. Mediat. Inflamm. 2015 [cited 2019 Nov 24]; 2015: 1–11. Publisher Full Text Reference Source\n\nFakheran O, Saied-Moallemi Z, Khademi A, et al.: Oral Health-Related Quality of Life during Pregnancy: A Systematic Review. Curr. Pharm. Des. 2020; 26(32): 4014–4021. PubMed Abstract | Publisher Full Text\n\nYenen Z, Ataçağ T: Oral care in pregnancy. J. Turk. Ger. Gynecol. Assoc. 2019 Dec 1 [cited 2020 Apr 28]; 20(4): 264–268. 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Reference SourceReference Source\n\nBahri N, Tohidinik HR, Bahri N, et al.: Educational intervention to improve oral health beliefs and behaviors during pregnancy: a randomized-controlled trial. J. Egypt. Public Health Assoc. 2015; 90(2): 41–45. PubMed Abstract | Publisher Full Text\n\nBasheer NA, Jodalli P: Effectiveness of Motivational Interviewing and cross platform messaging application in improving oral health knowledge, attitude and behaviours among pregnant women- a Randomized Controlled Trial. figshare. 2024 [cited 2024 Jun 18]. Publisher Full Text\n\nBansal K, Kharbanda OP, Sharma JB, et al.: Effectiveness of an integrated perinatal oral health assessment and promotion program on the knowledge in Indian pregnant women. J. Indian Soc. Pedod. Prev. Dent. 2019; 37: 383–391. PubMed Abstract | Publisher Full Text\n\nGreene JC, Vermillion JR: The simplified oral hygiene index. J. Am. Dent. Assoc. 1964; 68: 7–13. Publisher Full Text\n\nLoe H, Silness J: Periodontal Disease In Pregnancy. I. Prevalence And Severity. Acta Odontol. Scand. 1963 Dec; 21: 533–551. PubMed Abstract | Publisher Full Text\n\nDíaz-Guzmán LM, Castellanos-Suárez JLLesions of the oral mucosa and periodontal disease behavior in pregnant patients.Med. Oral Patol. Oral Cir. Bucal.2004 Nov-Dec; 9(5): 434–7; 430-3. English, Spanish. PMID: PubMed Abstract\n\nNew York State Department of Health: Oral Health Care during Pregnancy and Early Childhood Practice Guidelines. New York State Department of Health; 2016.\n\nHall K, Gibbie T, Lubman DI: Motivational interviewing techniques - facilitating behaviour change in the general practice setting. Aust. Fam. Physician. 2012 Sep; 41(9): 660–667. PubMed Abstract\n\nBaker A, Hambridge J: Motivational Interviewing: Enhancing engagement in treatment for mental health problems. Behav. Chang. 2002; 19: 138–145. Publisher Full Text\n\nZhuang R, Xiang Y, Han T, et al.: Cell phone-based health education messaging improves health literacy. Afr. Health Sci. 2016; 16(1): 311–318. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLim MS, Hocking JS, Aitken CK, et al.: Impact of text and email messaging on the sexual health of young people: a randomised controlled trial. J. Epidemiol. Community Health. 2012; 66(1): 69–74. PubMed Abstract | Publisher Full Text\n\nGold J, Lim MS, Hocking JS, et al.: Determining the impact of text messaging for sexual health promotion to young people. Sex. Transm. Dis. 2011; 38(4): 247–252. PubMed Abstract | Publisher Full Text\n\nIbrahim HM, Mudawi AM, Ghandour IA: Oral health status, knowledge and practice among pregnant women attending Omdurman maternity hospital. Sudan. East Mediterr. Health J. 2017 Feb 1; 22(11): 802–809. PubMed Abstract | Publisher Full Text\n\nAvula H, Mishra A, Arora N, et al.: KAP assessment of oral health and adverse pregnancy outcomes among pregnant women in Hyderabad, India. Oral Health Prev. Dent. 2013; 11: 261–270. PubMed Abstract | Publisher Full Text\n\nPentapati KC, Acharya S, Bhat M, et al.: Knowledge of dental decay and associated factors among pregnant women: A study from rural India. Oral Health Prev. Dent. 2013; 11: 161–168. PubMed Abstract | Publisher Full Text\n\nMartnez-Beneyto Y, Vera-Delgado MV, Prez L, et al.: Self-reported oral health and hygiene habits, dental decay, and periodontal condition among pregnant European women. Int. J. Gynaecol. Obstet. 2011 Jul; 114(1): 18–22. PubMed Abstract | Publisher Full Text\n\nBamanikar S, Kee LK: Knowledge, attitude, and practice of oral and dental healthcare in pregnant women. Oman Med. J. 2013; 28(288): 291.\n\nGeorge A, Johnson M, Blinkhorn A, et al.: The oral health status, practices and knowledge of pregnant women in south-western Sydney. Aust. Dent. J. 2013; 58: 26–33. PubMed Abstract | Publisher Full Text\n\nGupta N, Chhetry M: Knowledge and practices of pregnant women regarding oral health in a Tertiary Care Hospital in Nepal. J. Nepal Med. Assoc. 2019; 57: 184–188. Publisher Full Text\n\nGaffield ML, Gilbert BJ, Malvitz DM, et al.: Oral health during pregnancy: An analysis of information collected by the pregnancy risk assessment monitoring system. J. Am. Dent. Assoc. 2001; 132: 1009–1016. Publisher Full Text\n\nRocha JS, Arima LY, Werneck RI, et al.: Determinants of dental care attendance during pregnancy: A systematic review. Caries Res. 2018; 52: 139–152. PubMed Abstract | Publisher Full Text\n\nGupta R, Acharya AK: Oral Health Status and Treatment Needs among Pregnant Women of Raichur District, India: A Population Based Cross-Sectional Study. Scientifica (Cairo). 2016; 2016: 1–8. Publisher Full Text\n\nKashetty M, Kumbhar S, Patil S, et al.: Oral hygiene status, gingival status, periodontal status, and treatment needs among pregnant and nonpregnant women: A comparative study. J. Indian Soc. Periodontol. 2018; 22(2): 164–170. PubMed Abstract | Publisher Full Text\n\nCohen DW, Friedman L, Shapiro J, et al.: A longitudinal investigation of the periodontal changes during pregnancy. J. Periodontol. 1969; 40(563): 70.\n\nSteinberg BJ: Women’s oral health issues. J. Dent. Educ. 1999; 63: 271–275. 5., Loee H. Periodontal changes in pregnancy. J. Periodontol. 1965;36:209 17. Publisher Full Text"
}
|
[
{
"id": "319433",
"date": "05 Sep 2024",
"name": "Amit Vasant Mahuli",
"expertise": [
"Reviewer Expertise Public Health Dentistry",
"Oral Cancer",
"School Oral Health",
"Epidemiology of oral health and systematic review & meta-analysis"
],
"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 Its a well reported study. However, the following observations can be considered: 1. Some text is redundant from introductory lines of methodology and inclusion criteria's 2. Even though the sample size is calculated, the sample size is small. The results are conclusive in favour of the motivational interviewing, but there are inherent advantages and disadvantages to both methods. Recommendations and limitations of the study are very well mentioned. 3. The loss to follow up analysis, either Intention treat or Per-protocol analysis used, has to be justified 4. The data on accessibility to health care service and location, either urban or rural, can give better insights in relation to the title. Overall, it is a well written article highlighting the importance of oral health awareness and prevention of oral health disease in pregnant women\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": "319429",
"date": "10 Sep 2024",
"name": "Atrey J Pai khot",
"expertise": [
"Reviewer Expertise Infectious Disease Control and Prevention / Public Health / Dental Public Health / Epidemiology / Alternative Medicine / Dentistry / Randomized Clinical Trials / Meta-Analysis / Tobacco Control / Community Health Care / Special Health Care/ Health Education and Promotion"
],
"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 of good scientific interest. The selection of such an important research area demonstrates the author’s deep understanding of difficulties in health promotion among pregnant women. The findings presented in this article have the potential for decision-making in the context of oral health care in pregnant women. Well-conducted research with meticulous study design. Overall results are presented in a logical and comprehensible manner.\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": "319432",
"date": "26 Sep 2024",
"name": "Ankita jain",
"expertise": [
"Reviewer Expertise biostatistics",
"community engagement",
"environmental health",
"epidemiology",
"global health",
"health policy and management",
"and health promotion and socio-behavioural health sciences."
],
"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 \"Effectiveness of Motivational Interviewing and Cross-Platform Messaging Application in Improving Oral Health Knowledge, Attitude, and Behaviors Among Pregnant Women: A Randomized Controlled Trial\" presents a timely and relevant investigation. The study's design is robust, employing a randomized controlled trial approach, which strengthens the validity of the findings. Both motivational interviewing and the use of a messaging application show promising potential for enhancing oral health awareness in this vulnerable population. The authors effectively address the research questions and provide clear implications for practice. I recommend acceptance, with minor revisions for clarity in methodology and data presentation.\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/13-871
|
https://f1000research.com/articles/13-867/v1
|
01 Aug 24
|
{
"type": "Research Article",
"title": "More foreign-accented but more comprehensible: Attrition and amelioration of L1 speech in proficient L2 learners",
"authors": [
"Kakeru Yazawa",
"Takayuki Konishi",
"Rubén Pérez-Ramón",
"Mariko Kondo",
"Takayuki Konishi",
"Rubén Pérez-Ramón",
"Mariko Kondo"
],
"abstract": "Background There is an increasing interest in cross-linguistic influences of the second language (L2) on the first (L1), but its communicative impact remains to be elucidated. This study investigates how L2 learners’ L1 pronunciation is perceived as foreign-accented and (in) comprehensible as a function of their L2 learning experience and proficiency levels.\n\nMethods Read speech of 154 L1 Japanese learners of L2 English in the J-AESOP corpus was examined, where approximately one-third of them had lived in English-speaking countries and the rest had never lived outside of Japan. Their L1 speech was rated by another group of native Japanese listeners for accentedness and comprehensibility (from October 25, 2022 to August 20, 2023), while their L2 speech was previously rated by native American English listeners for nativelikeness or proficiency. The speakers’ vowel acoustics were also examined.\n\nResults More proficient L2 speakers were perceived as more foreign-accented in their L1, but only if they had lived overseas; their length of residence abroad predicted the degree of perceived accentedness. In contrast, more proficient L2 speakers were consistently perceived as more comprehensible in the L1, regardless of prior overseas experience. Acoustic analyses indicated that perceived accentedness is associated with a clockwise chain shift of all vowel categories in the vowel space. It was also revealed that the dispersion, rather than compactness, of vowel production contributed to perceived comprehensibility, although the degree of L1 vowel dispersion did not predict L2 proficiency.\n\nConclusions The overall results suggest two main conclusions. First, perceptible L1 foreign accent likely results from L1 disuse rather than L2 interference, thereby L1 pronunciation differs from native norms at a system-wide rather than category-specific level. Second, L2 learning has a positive influence on perceived L1 comprehensibility, rather than individuals with clearer and more comprehensible L1 speech being inherently better L2 learners.",
"keywords": [
"Foreign accent",
"comprehensibility",
"proficiency",
"length of residence",
"phonetic attrition",
"J-AESOP corpus",
"category compactness",
"vowel dispersion"
],
"content": "1. Introduction\n\n“Foreign accent” is a term commonly used to refer to speech characteristics that differ from what native speakers recognize as a native accent. It is usually used in a situation where a speaker’s first language (L1) affects their second language (L2), a phenomenon known as “forward transfer” (or simply “transfer”), which has been widely studied in the field of L2 speech research (e.g., Kondo and Pérez-Ramón (2023) and Yazawa et al. (2023a) on Japanese-accented English). However, foreign accents can also emerge in the ‘opposite’ situation, that is, when a speaker’s L2 learning experience affects their L1 pronunciation (de Leeuw et al., 2010; Kornder, 2022; Laméris et al., 2024). This phenomenon, sometimes called “backward transfer” (Cook, 2003), has received increasing attention in recent years, although much remains to be elucidated about its nature. The purpose of the current study is to address some of the less documented issues in phonetic backward transfer, including its impact on perceived L1 accentedness and comprehensibility, in relation to the speaker’s L2 learning experience and proficiency levels.\n\nGiven the recent surge of interest in phonetic backward transfer, with various terms used to describe its specific aspects, it is important to clarify the terminology that we will use in this study. One of the most commonly used terms for L2-induced L1 pronunciation change is “phonetic drift” (Chang, 2019). While the term itself was first introduced by Sapir (1921) to refer to diachronic sound change in ‘macro’ language (i.e., language at the level of the speech community, such as English) and is still used in that sense, our use of the term follows that of Chang (2019) in that we refer to sound change over time within ‘micro’ language (i.e., language at the level of the individual, namely an idiolect). The precise definition we adopt from Chang (2019) is “L2-influenced phonetic change in an individual’s L1 system” (p. 191) that is “short-term” (p. 192) and “attributable to recent L2 experience” (p. 192). When this drift becomes chronic due to cumulative use of the L2, we use the term “phonetic attrition” (de Leeuw, 2019). Attrition can, in an extreme case, cause a bilingual’s L1 speech to be perceived as foreign-accented by monolingual listeners of the language, although this does not necessarily imply that short-term phonetic drift never affects the perceived accentedness of L1 speech. To encompass both cases of drift and attrition, we will also employ a more general (but lesser-used) umbrella term, “phonetic change,” in this paper.\n\nThe growing body of literature on L1 phonetic change has been thoroughly reviewed by Kartushina et al. (2016). The paper identifies several factors that seem to affect the likelihood and magnitude of phonetic change, such as the age of onset (AoO) of L2 acquisition, the level of L2 proficiency, and the amount of L1 use, among others. The reviewed findings can be summarized as follows: whereas simultaneous bilinguals are capable of attaining and maintaining nativelike competence in both languages, sequential bilinguals are more prone to L1 phonetic drift and attrition; even novice L2 learners can show L1 drift due to ‘novelty’ effects, which is somewhat diminished for intermediate learners, whereas highly proficient L2 speakers show signs of attrition; less frequent L1 use, which is often concordant with L2 dominance and proficiency, results in greater L1 phonetic change. However, one of the main challenges in this type of setting, where the speaker is fully immersed in an L2-speaking—and thus non-L1-speaking—environment, is that the above factors are difficult to disentangle from each other. For example, the effect of L2 proficiency is intertwined with that of L1 disuse, as they often go hand in hand (especially in migrant settings). This is one of the key issues that we aim to unravel in the current study.\n\nA fundamental assumption underlying many of the previous studies on L1 phonetic change is that the phenomenon is driven by the developing and newly established sound categories in the learner’s L2 system. This assumption derives largely from the (revised) Speech Learning Model (SLM(-r); Flege, 1995; Flege & Bohn, 2021), which proposes that L1 and L2 phonetic categories exist in a common space and constantly influence each other in a bidirectional manner. Thus, studies have reported cases where an L1 segmental category assimilates (i.e., moves closer) to or dissimilates (i.e., moves away) from its closest L2 category, with the AoO being a potential factor affecting which process takes place (see Kartushina et al. (2016) for details). However, other studies have suggested an alternative possibility that L1 phonetic change occurs at a broader, system-wide level. Guion (2003) investigated L1 Quechua speakers who differed in their L2 Spanish AoO and found that L1 Quechua vowels of early bilinguals (who acquired a five-vowel system for the L2) generally had lower first formant (F1) values than those of late bilinguals (who maintained a three-vowel, L1 Quechua-like system). This suggests that learning new L2 Spanish vowel categories shifted the L1 Quechua vowel space upward, which cannot be explained by segment-by-segment assimilation (or dissimilation) between the two languages since not all Spanish vowels are higher (or lower) than in Quechua. The author proposed that this system-wide raising of L1 vowels serves to enhance their perceptual distinctiveness from the L2 vowels. Mayr et al. (2012) and Turner (2023) reported similar cases but in the opposite direction, where increased L2 exposure caused a systematic increase in F1 values (i.e., downward shift) of all L1 vowels, in Dutch-English bilinguals and L1 English learners of L2 French, respectively. An important finding of Turner’s (2023) longitudinal study is that learners showed a partial reversal of phonetic drift after re-immersion into the L1-speaking environment, which again occurred at a system-wide rather than category-specific level. Interestingly, none of the above three studies observed a change in second formant (F2) frequencies.\n\nThe majority of previous research has focused on how L1 phonetic change occurs at the acoustic level, including F1 and F2 frequencies of vowels, voice onset time (VOT) of stops, center of gravity of fricatives, to name a few. The communicative impact of such acoustic changes, however, has been relatively understudied. De Leeuw et al. (2010) found that L1 German speakers who had moved to Canada or to the Netherlands at an average age of 27 and had lived there for an average of 37 years were perceived as having a noticeable foreign accent, with some even being recognized as non-native speakers. A longitudinal study by Kornder (2022) also found that Arnold Schwarzenegger, who was born in Austria in 1947 and moved to the United States in 1968, has a perceptible foreign accent in his recent L1 German (2010-2017) that was absent in the early stage of his career (1977-1989). More relevant to the current study, Laméris et al. (2024) examined accentedness ratings of Japanese-English bilingual returnees (Japanese children who returned to Japan after living in an English-speaking environment for several years) at three time points (upon return to Japan, one year after return, and five years after return) and found a decrease in L1 foreign accent as early as one year after return; the overall degree of L1 accentedness was more pronounced for returnees with earlier English AoO and increased L2 exposure while abroad. Taken together, these studies suggest that L2 learning experience can affect the perceived ‘authenticity’ of L1 speech, which seems to be reversible to some extent after re-immersion into the L1 environment. However, it remains unclear which acoustic characteristics contribute to the degree of perceived foreign accentedness and how. Also, the effects of L1 phonetic change on perceived comprehensibility (i.e., how easy an utterance is to understand) has rarely been studied. The only study we are aware of that addressed the above two points is Kornder (2022), who found a change in stop VOT and vowel formants but no significant difference in perceived comprehensibility between early and late L1 productions of Arnold Schwarzenegger. However, due to the nature of the study focusing on one speaker, it is not known how generalizable the results are.\n\nBased on the literature reviewed above, the current study aims to address the following research questions to shed more light on the communicative impact of L1 phonetic change. Our first question concerns the perceived accentedness of L1 speech: what is the source of L1 foreign accent, L2 interference or L1 disuse? Since all of the previous studies on L1 foreign accent reviewed above (de Leeuw et al., 2010; Kornder, 2022; Laméris et al., 2024) investigated a migrant population that had been using their L2 as their dominant language for many years, it is unclear whether their L1 accent is caused by an interference from the L2 system or by a long-term disuse of the L1 system. Our second question is related to the first: does L1 foreign accent reflect a category-specific process or a system-wide shift? Regardless of the source of L1 accent, the L1 system of foreign-accented speakers should exhibit some acoustic characteristics that are absent in or different from non- and less-accented speakers, which may take the form of individual L1 sound categories assimilating or dissimilating to L2 categories, as is usually assumed, or of all L1 categories changing at a systematic level, as some studies have suggested (Guion, 2003; Mayr et al., 2012; Turner, 2023). Finally, our third question concerns the comprehensibility of L1 speech: what is the influence of L2 learning on L1 comprehensibility? In the case of forward transfer, it is known that a strong degree of accentedness does not necessarily imply a loss of comprehensibility or intelligibility (Munro & Derwing, 1995). However, the same pattern may not necessarily hold for backward transfer because, according to Cook (2003), the effects of the L2 on the L1 can be positive (e.g., enhanced metalinguistic skills), negative (e.g., loss of L1 competence), or neutral (not ‘better’ or ‘worse’ but simply ‘different’).\n\nTo answer these questions, we conduct a large-scale rating study of perceived accentedness and comprehensibility in L1 Japanese speech of L2 English learners with diverse learning experience and proficiency levels, using the J-AESOP corpus (Kondo et al., 2015). The current study builds on our previous pilot investigation using the same corpus (Yazawa et al., 2023b), which suggested a potential influence of L2 proficiency on L1 accentedness and comprehensibility, but this finding needs to be confirmed with more raters than was tested (n = 10). Our previous study also did not probe into the speakers’ L2 learning experience (e.g., whether they had lived in an L2-speaking environment and for how long) and the acoustic characteristics of the speech, which we aim to complement in the current investigation. In what follows, we first present the rating results in Section 2, followed by the acoustic analysis in Section 3. Section 4 discusses the implications of the results, limitations of the current study, and directions for further research.\n\n\n\n\n2. Perceptual rating\n\nThe J-AESOP corpus contains speech data of 183 L1 Japanese learners of L2 English as well as 20 L1 English learners of L2 Japanese. The current study focuses on 154 L1 Japanese speakers (94 female, 60 male) who had never lived overseas in a non-English-speaking country (e.g., Spain) in order to control for the potential influence of a third language (L3). The speakers were all undergraduate or graduate students at universities in and around Tokyo, Japan, between the ages of 18 and 38 (mean = 20.04, standard deviation = 2.10). Approximately two-thirds of them (n = 99; 50 female, 49 male) had spent their entire lives in Japan, with most of them having studied English for six years (age 13-18) as part of their compulsory education in secondary schools. They had also received some English instruction in college, the quality and quantity of which varied depending on the courses in which they were enrolled. The remaining third (n = 55; 44 female, 11 male) had some experience of living in an English-speaking country (32 in the US, 10 in the UK, nine in Australia, eight in Canada, three in New Zealand, with some having lived in more than one country), with the length of residence (LOR) ranging from one month to 11 years (mean = 27.45 months, standard deviation = 32.46 months), but none of them were considered simultaneous bilinguals. Their language learning background while in Japan was similar to that described above, except that some speakers attended international schools as part of their secondary education.\n\nThe speech materials to be rated are taken from Tasks 6_01 and 6_02 of the J-AESOP corpus, where the speakers read aloud the English and Japanese versions of “The North Wind and the Sun” (International Phonetic Association, 1999) shown in Table 1 and Table 2, respectively. The trisecting of the text in Table 1 is for rating purposes only (see Section 2.4.1), and the speakers read the passage as a whole.\n\n2.3.1 English raters\n\nFour phonetically trained native American English listeners were recruited to rate the audio samples of Task 6_01 as part of a previous research project (Konishi, 2022). All of them had a graduate degree in phonetics or a related field and were familiar with the L2 English pronunciation of L1 Japanese speakers. Such experienced raters are known to be able to consistently rate various aspects of speech, including segmental accuracy, word stress, intonation, and rhythm (Saito et al., 2017).\n\n2.3.2 Japanese raters\n\nTwenty-six native Japanese listeners (22 female, 4 male) were recruited to rate the audio samples of Task 6_02 for the current study (this sample includes the 10 listeners in Yazawa et al. (2023b)). They were all undergraduate or graduate students at the University of Tsukuba, Ibaraki, Japan, between the ages of 19 and 25 (mean = 21.04, standard deviation = 1.93). Twenty of them had never lived outside of Japan, while the remaining six had studied abroad in an English-speaking country (three in the UK, two in the US, and one in Australia) for one to ten months. Although the raters were not as linguistically experienced as the four native American English raters, it has been shown that such listeners can coherently evaluate global accentedness and comprehensibility (Saito et al., 2017).\n\n2.4.1 English rating\n\nThe native American English listeners were provided with all the trisected audio samples of Task 6_01 for self-paced rating. They were instructed to listen to each trisection and rate the speech according to four criteria (segmental accuracy, prosody, fluency, and nativelikeness) on a 10-point scale each. The current study focuses on the nativelikeness score, where a value of 1 corresponds to “strongly foreign-accented” and a value of 10 corresponds to “free of foreign accent.” Once the rating was completed, the obtained scores were averaged across the trisections per speaker, yielding a single nativelikeness score for each speaker as assessed by one rater. The trisection scheme was to improve the accuracy of the rating by having a rater evaluate the same speaker three times, which also made the resulting scores non-integer (i.e., 1.00, 1.33, 1.67, etc.). Raters received monetary compensation for their time and effort. More details of the English rating can be found in Konishi (2022).\n\n2.4.2 Japanese rating\n\nThe native Japanese listeners rated the audio samples of Task 6_02 online via Gorilla Experiment Builder (Anwyl-Irvine et al., 2020). They signed a written consent form and completed a language background questionnaire prior to participation. After a brief tutorial and a practice session, the raters listened to a speaker’s audio sample presented in random order. The use of headphones or earphones was encouraged, but not required, since the use of headphones is unlikely to have any substantial effect on the results of most online perception experiments (Sanker, 2023). The raters then indicated the perceived impression of global accentedness and comprehensibility using two horizontal sliders. The slider for accentedness read “strong foreign accent” on one end and “no foreign accent” on the other, and the slider for comprehensibility read “difficult to understand” on one end and “easy to understand” on the other, in Japanese. The slider values were internally coded from 0 to 100 with integer increments, with a larger value corresponding to a higher level of perceived accentedness or comprehensibility. A pause screen was displayed after each trial to allow the raters to take a short break at any time during the rating. All raters completed their ratings within one week and received monetary compensation for their time and effort. The language background of the speakers was disclosed only after they completed the task.\n\nThe above procedural design, including the consent form and the questionnaire, was reviewed and approved by the Research Ethics Committee of the Institutes of Humanities and Social Sciences, University of Tsukuba on May 17, 2022 (approval number 2022-3). All procedures were conducted in accordance with the ethical standards of the Helsinki Declaration.\n\n2.5.1 English scores\n\nFigure 1 shows the mean L2 English nativelikeness scores of all 154 L1 Japanese speakers (averaged across four native American English raters), conditioned by their presence and absence of previous residence in an English-speaking country. The intraclass correlation coefficient (ICC) using a two-way random-effects model for consistency (Koo & Li, 2016) was 0.892, indicating a very high level of inter-rater consistency. It can be seen that the scores are fairly evenly distributed, ranging from nearly 1 (“strongly foreign-accented”) to 10 (“free of foreign accent”). While speakers with overseas experience (i.e., LOR > 0) tend to have higher scores than those without (i.e., LOR = 0), there is a significant overlap in L2 nativelikeness score between the two groups (i.e., LOR > 0 vs. LOR = 0). Therefore, by-group investigation of the data would help us to disentangle the potential effect of L2 proficiency (as represented by nativelikeness score) from that of L1 disuse associated with overseas experience (as represented by LOR).\n\n2.5.2 Japanese scores\n\nFigure 2 shows the mean L1 Japanese accentedness and comprehensibility scores of the same 154 speakers (averaged across 26 native Japanese raters), conditioned by their previous experience of overseas residence. The ICC was 0.279 for accentedness and 0.271 for comprehensibility, indicating a weak but acceptable level of inter-rater consistency (Fleiss & Cohen, 1973). The confidence ellipses for L1 accentedness scores indicate that most speakers were not perceived as very accented, although some speakers, those with overseas experience (i.e., LOR > 0) in particular, were judged to be moderately accented. The ellipses for L1 comprehensibility scores indicate that most speakers were perceived as generally comprehensible, with a few speakers without overseas experience (i.e., LOR = 0) being apparent outliers. The two types of scores are negatively correlated (Pearson’s r = -0.62), suggesting that more accented speech tended to be perceived as less comprehensible. However, it is still possible that these score types are differentially related to L2 experience and proficiency, as will be illustrated below.\n\n2.5.3 Relationship between English and Japanese scores\n\nFigure 3 shows the relationship between the L2 English and L1 Japanese scores, again conditioned by the speakers’ overseas experience. Regarding the L1 accentedness score (left side of the figure), distinct patterns can be identified between the two LOR groups. For speakers with LOR > 0, a higher L1 accentedness score seems to be associated with a slightly higher L2 nativelikeness score, suggesting that more proficient L2 speakers tended to be perceived as more foreign-accented in their L1 speech. Given that there was a positive correlation between LOR (in months) and L2 nativelikeness score for these speakers (Pearson’s r = 0.59), this may also suggest that the longer they had stayed in an English-speaking country, the more accented their Japanese was judged to be. This explanation is further supported by the opposite pattern observed for speakers with LOR = 0, where a higher L1 accentedness score seems to be associated with a lower L2 nativelikeness score. Taken together, these results suggest that the experience of living overseas, rather than L2 proficiency per se, contributes to perceived L1 accentedness. In contrast, regarding L1 comprehensibility (right side of the figure), both LOR groups show the same tendency where a higher L1 comprehensibility score leads to a higher L2 nativelikeness score. This suggests that more proficient L2 speakers were generally perceived as more comprehensible in their L1 speech, regardless of prior experience abroad.\n\nTo test whether the above observations hold at statistically significant levels, a cumulative link mixed model (CLMM) was fitted to the response data per speaker group (i.e., LOR = 0 or LOR > 0), using the ordinal package (Christensen, 2023) in R (R Core Team, 2024). The structure of the model was as follows:\n\nTo further examine the effect of LOR on L1 accentedness scores, we also fitted the following linear mixed effects (LME) model, using the lme4 (Bates et al., 2015) and lmerTest (Kuznetsova et al., 2017) packages in R:\n\n\n3. Acoustic analysis\n\nThe above analysis of the rating data suggests that more proficient L2 speakers tend to be perceived as more foreign-accented and yet more comprehensible in their L1 speech, except that those who have never lived abroad do not seem to gain an L1 foreign accent as they become more proficient in the L2. It remains to be seen, however, based on what acoustic characteristics the L1 speech was judged to be foreign-accented and comprehensible. To probe into this issue, we examine in this section the speakers’ L1 Japanese vowel production in relation to their accentedness and comprehensibility scores. We also refer to the same speakers’ L2 English vowel production and their nativelikeness scores to complement the analysis (cf. Yazawa et al., 2023a).\n\n3.1.1 Materials\n\nThe audio recordings of Tasks 6_01 and 6_02 in the J-AESOP corpus (see Section 2.2) were examined. The speech samples were annotated in Praat TextGrid format (Boersma & Weenink, 2024), first by automatic forced alignment tools (HTK (Young et al., 2006) for Task 6_01 and Julius (Lee & Kawahara, 2019) for Task 6_02) and then manually modified by trained phoneticians in the J-AESOP team. Annotators also marked segment-level phonological events such as vowel devoicing (e.g., /kitakaze/ ‘North Wind’ ➔ [ki̥takaze]) and lengthening (e.g., /taijou/ ‘Sun’ ➔ [taijoː]) in Japanese, as well as word-level speech events such as substitution (e.g., misreading cloak as coat), repetition (e.g., Then the Sun … Then the Sun shone out warmly), and insertion (e.g., wrapped around in a warm cloak) by assigning ‘tags’ to the relevant words (underlined above).\n\n3.1.2 Data retrieval and acoustic measurement\n\nBased on the annotations, a total of 34963 Japanese vowels (/i/ = 6504, /e/ = 3598, /a/ = 15713, /o/ = 6504, /u/ = 2444) produced by the 154 L1 Japanese speakers were retrieved for acoustic analysis. Their production of 10775 English monophthongal vowels (/i/ = 1591, /ɪ/ = 3196, /ɛ/ = 911, /æ/ = 1451, /ʌ/ = 1094, /ɑ/ = 1095, /u/ = 893, /ʊ/ = 544) was also retrieved. Devoiced and lengthened vowels, as well as vowels in tagged words, were excluded.\n\nFor each vowel interval, the mean F1 and F2 frequencies were measured using Praat. The built-in Burg algorithm was used for formant estimation, with the formant ceiling setting at 5000 Hz for male speakers and 5500 Hz for female speakers. The obtained F1 and F2 values were then Z-transformed per speaker (Lobanov, 1971), which effectively eliminates spectral variations caused by physiological differences while preserving phonological and cross-linguistic contrasts (Adank et al., 2004). The normalization was performed across Tasks 6_01 and 6_02 so that the formants could be directly compared across L1 Japanese and L2 English speech.\n\nWe begin our analysis by examining the potential acoustic correlates of perceived L1 foreign accent. Given the finding in Section 2 that L1 foreign accented was typical of L2 speakers with overseas experience, here we focus on the 55 speakers with LOR > 0. We first hypothesized that the formant values of L1 vowels in foreign-accented speech are dislocated from those of non- or less-accented speech, presumably due to the assimilation or dissimilation of L1 vowels to acquired L2 vowels. To test this, we used the following LME model:\n\nTo complement the above results, we also show in Figure 4 the production of L2 English vowels by the same 55 speakers as a function of their L2 nativelikeness scores (cf. Yazawa et al. (2023a)). Each circle shows the mean Z-normalized formant values of a 0.50 score range (i.e., 1.25-1.75, 1.75-2.25, etc., as in the bins of Figure 1), with darker shades representing higher scores. The arrows point from lowest through intermediate to highest score ranges based on these means, ignoring apparent outliers. The mean formant values of L1 Japanese vowels are also shown alongside as gray boxes (averaged across the L2 score ranges because the by-range differences in F1 and F2 values were too subtle to plot). Since speakers with higher L2 nativelikeness scores were perceived as having a stronger L1 foreign accent for the current sample, a comparison of Table 6 and Figure 4 can be useful to examine how acquired L2 vowels might affect L1 vowel production.\n\nThe comparison shows that only some of the results can be straightforwardly explained by L1-L2 segmental assimilation or dissimilation. For example, the results for L1 /e/ in Table 6, where lower F1 and higher F2 values predict a higher L1 accentedness score, can be interpreted as a case of dissimilation from the adjacent L2 vowel /ɛ/, which shows the opposite pattern as a function of L2 nativelikeness score in Figure 4. That is, as speakers become more proficient in the L2 (and thus more accented in the L1), their L1 /e/ production is raised and fronted while that of L2 /ɛ/ is lowered and backed, resulting in an increased distance between the two categories. In contrast, the results for L1 /o/ in Table 6, where higher F1 and lower F2 values predict a higher L1 accentedness score, can be interpreted as a case of assimilation to L2 /ɑ/, which shows the same pattern according to L2 nativelikeness scores in Figure 4. That is, as speakers become more proficient in the L2 (and thus more accented in the L1), the L1 and L2 vowels move to the same direction (similar to what Turner (2023) called “tandem drift”). The results for the other three L1 vowels, however, were more mixed. As for /i/, while the negative estimate for F1 (i.e., raising) in Table 6 may be attributed to its assimilation to L2 tense /i/ (see Figure 4), the negative estimate for F2 (i.e., backing) would contrarily indicate dissimilation from this very L2 category. The same goes for L1 /u/, where the negative F1 estimate (i.e., raising) would indicate assimilation to L2 /u/ or /ʊ/, whereas the negative F2 estimate (i.e., backing) would indicate dissimilation from these two categories. L1 /a/ is a similar case, where the positive F1 estimate (i.e., lowering) would indicate dissimilation from L2 /æ/ or /ʌ/, while the positive F2 estimate (i.e., fronting) would indicate assimilation to these categories. The supposed assimilation-dissimilation patterns are, therefore, inconsistent at best.\n\nAnother explanation becomes possible when we shift our focus from individual L1-L2 category contrasts to the whole vowel space. Considering the suggested phonetic changes in Table 6—raising and backing of /i/, raising and fronting of /e/, lowering and fronting of /a/, lowering and backing of /o/, and raising and backing of /u/—one can envision a clockwise chain shift. Judging from Figure 4, such movements of L1 vowels seem to be helpful for maintaining their distance from the developing L2 categories.\n\nWe now move on to examine the potential acoustic correlates of perceived L1 comprehensibility. Here we investigate all 154 speakers, since more proficient L2 speakers were found to be more comprehensible in their L1 regardless of overseas experience in Section 2. The first acoustic parameter to be investigated is the ‘compactness’ of vowel categories in the F1-F2 acoustic space. Kartushina and Frauenfelder (2014) found that individuals with more compact L1 vowel categories tend to show more accurate L2 vowel production, presumably because the existing L1 categories overlap less with the target L2 vowels. SLM-r (Flege & Bohn, 2021) provides a theoretical explanation of this finding through its “category precision” hypothesis, which posits that individuals with relatively precise L1 categories are better able to discern phonetic differences between an L2 sound and the closest L1 sound, thereby increasing the likelihood of new L2 category formation. If this is also true for the current sample, we can hypothesize that higher L1 comprehensibility in more proficient L2 learners is also due to their more compact or precise production of L1 vowel categories.\n\nFollowing Kartushina and Frauenfelder (2014), we first calculated the compactness score (CS) per speaker and vowel type, using the following formula:\n\nThe calculated five CSs were then added to obtain the global compactness score (CSG) per speaker:\n\nAnother acoustic parameter we will investigate here is formant dispersion, since compact vowel categories can still overlap with one another if they are not sufficiently dispersed and non-compact vowel categories can still be clearly distinguishable from each other if they are sufficiently dispersed. Thus, we can derive an alternative hypothesis that higher L1 comprehensibility in more proficient L2 learners is due to their more dispersed L1 vowel production.\n\nWhile there are several metrics for measuring formant dispersion, we used the vowel formant dispersion (VFD) metric of Karlsson and van Doorn (2012). To calculate the VFD, we first need to define the center of the F1-F2 vowel space for each speaker. The coordinate of the midpoint along the vertical (F1) axis is calculated according to:\n\nNow that the acoustic parameters are defined, the question is whether individual differences in vowel compactness or dispersion predict the degree of perceived L1 comprehensibility. To test this, we used the following LME model:\n\nTo fully support the second hypothesis, however, we must also demonstrate that individuals with more dispersed L1 vowel production are more proficient in the L2. To test this, we fitted the following CLMM:\n\n\n4. General discussion\n\nThe primary purpose of the current study was to investigate the potential effects of L2 learning on perceived accentedness and comprehensibility of L1 speech. To this end, we examined 154 L1 Japanese learners of L2 English in the J-AESOP corpus with varied L2 learning experience and proficiency levels. The rating results revealed that more proficient L2 speakers tended to be perceived as more foreign-accented in the L1, but only if they had lived in an English-speaking country; no such relationship was found for those who had never lived abroad. Subsequent acoustic analyses of vowel production suggested that the degree of perceived foreign accent could not be straightforwardly attributed to either assimilation or dissimilation of individual L1 and L2 categories but rather to a system-wide phonetic change. In contrast, more proficient L2 speakers were consistently perceived as more comprehensible in the L1, regardless of the presence or absence of prior overseas experience. Acoustic analyses suggested that the degree of perceived comprehensibility was associated with the dispersion, rather than compactness, of vowel production, although neither dispersion nor compactness in L1 vowel production predicted L2 proficiency levels.\n\n4.2.1 Accentedness\n\nThe rating results for accentedness suggest that L2 learners do not necessarily gain an L1 foreign accent as they become proficient in the L2. Rather, strong L1 accentedness seems to be associated with the experience of living in an L2-speaking (or non-L1-speaking) environment for an extended period of time. Therefore, to answer our first research question, a perceptible L1 foreign accent is likely due to L1 disuse rather than L2 interference. It may thus be misleading to refer to this phenomenon as “backward transfer” because the acquired L2 system is not directly affecting the existing L1 system; the term “attrition” would be more appropriate in this sense. It should be noted, however, that the degree of perceived L1 foreign accent for the current sample was less profound than that of the migrant populations in the previous studies (de Leeuw et al., 2010; Kornder, 2022). This may be because our speakers maintained their L1 oral skills through everyday conversations with their parents and siblings while abroad and/or partially reversed L1 attrition after re-immersion into the L1-speaking environment back in Japan. While the LOR information in the corpus does not reflect these possibilities, the effects of relative L1 exposure while abroad and the length of L1 re-immersion in Japanese-English bilingual returnees is extensively discussed in Laméris et al. (2024).\n\nOur acoustic analysis of vowel production also indicated an intriguing pattern of potential L1 phonetic change in proficient L2 speakers with overseas experience: clockwise chain shift in the F1-F2 space. While no previous study has reported such a pattern, our finding would not contradict previous reports of system-wide phonetic change due to drift or attrition (Guion, 2003; Mayr et al., 2012; Turner, 2023). Thus, to answer our second research question, perceived L1 accent seems to reflect a system-wide change in all sound categories, rather than individual assimilation or dissimilation of adjacent categories between the two languages. Caution is warranted, however, because the previous studies observed a systematic lowering or raising of all vowel categories, whereas in the current study the direction of change varied from vowel to vowel (similar to Kornder (2022)). Nevertheless, the motivation for these diverging patterns may be the same, i.e., to maintain a perceptual distinction between the L1 and L2 sounds, as proposed by Guion (2003).\n\n4.2.2 Comprehensibility\n\nA novel finding of this study was that a higher level of L2 proficiency consistently predicted a higher level of L1 comprehensibility (consistent with our previous pilot study (Yazawa et al., 2023b)). This was somewhat surprising given the negative correlation between L1 accentedness and comprehensibility (cf. Figure 2), but perhaps not entirely unexpected since a strong foreign accent does not necessarily reduce perceived comprehensibility for L2 speech (Munro & Derwing, 1995). Thus, to answer our final research question, the influence of L2 learning on perceived L1 comprehensibility can be positive. Logically speaking, there are two possible explanations for the current finding: (i) learners whose L1 speech is comprehensible tend to acquire a high level of L2 proficiency, and (ii) as learners become more proficient in the L2, their L1 speech becomes more comprehensible. The first possibility was theoretically predicted by the “category precision” hypothesis of SLM-r (Flege & Bohn, 2021), as outlined in Section 3.3. However, the acoustic analyses did not support this prediction, since neither compactness nor dispersion of L1 vowel articulation was related to L2 nativelikeness scores (in contrast to Kartushina and Frauenfelder (2014) who found a link between L1 vowel compactness and L2 proficiency). It is then worth noting that the VFD metric did predict the perceived degree of L1 comprehensibility, because if this viable acoustic predictor of L1 comprehensibility does not predict L2 proficiency, then (i) is not very feasible. The alternative possibility is (ii), which, although no current model of L2 speech acquisition offers an explicit explanation for it, seems plausible in nature. If L2 learning involves an effort to clearly articulate speech sounds to make oneself better understood, then learners may extend this skill to their L1 production, thus increasing its comprehensibility (even though the resulting speech may differ from monolingual norms). If such an effect turns out to be true, then this L2-related ‘amelioration’ or ‘enrichment’ of L1 speech would be an important advantage of bilingualism, especially in the current era where comprehensibility is considered more important than nativelikeness.\n\nIn this study, we conducted a large-scale cross-sectional investigation of L1 phonetic change in native Japanese speakers with various L2 English learning experience and proficiency levels using the J-AESOP corpus. The overall results seem to suggest two main conclusions. First, perceived L1 foreign accent likely results from L1 disuse rather than L2 interference, where a learner’s L1 pronunciation is shifted from monolingual norms at a system-wide rather than category-specific level. Second, L2 learning can have a positive influence on perceived L1 comprehensibility, rather than individuals whose L1 speech is more comprehensible being better equipped for L2 learning. However, the current investigation is limited in that the corpus data do not inform us of how the learners’ pronunciation has actually changed over time; we are, after all, comparing different speakers from different linguistic backgrounds. What seems necessary to confirm and extend the current research, then, is a longitudinal study of intra-speaker acoustic-phonetic change and its communicative impact, similar to previous studies (e.g., Kornder (2022)) but with a larger number of speakers. To this end, a longitudinal bilingual speech corpus, which is far less common than cross-sectional ones such as J-AESOP, is expected to be useful. While building such a corpus would be labor-intensive and time-consuming, we believe that the benefits outweigh the effort. A preliminary project towards this goal has been initiated, and we look forward to sharing what it brings about in the future.\n\n\nEthics and consent\n\nThis study was reviewed and approved by the Research Ethics Committee of the Institutes of Humanities and Social Sciences, University of Tsukuba on May 17, 2022 (approval number 2022-3) and was conducted in accordance with the ethical standards of the Helsinki Declaration. Participants signed a written consent form prior to participation.",
"appendix": "Data availability\n\nZenodo: J-AESOP Rating Data (6_01 & 6_02). https://doi.org/10.5281/zenodo.10633636 (Konishi & Yazawa, 2024).\n\nThis project contains the following underlying data.\n\n• Rating6_01.csv\n\n• Rating6_02.csv\n\nThe demographic information and audio samples of the speakers in the J-AESOP corpus cannot be publicly shared because open posting of data on a repository was not included in the consent form at the time of data collection.\n\n\nReferences\n\nAdank P, Smits R, van Hout R : A comparison of vowel normalization procedures for language variation research. J. Acoust. Soc. Am. 2004; 116(5): 3099–3107. PubMed Abstract | Publisher Full Text\n\nAnwyl-Irvine AL, Massonnié J, Flitton A, et al.: Gorilla in our midst: An online behavioral experiment builder. Behav. Res. Methods. 2020; 52(1): 388–407. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBates D, Mächler M, Bolker BM, et al.: Fitting linear mixed-effects models using lme4. J. Stat. Softw. 2015; 67(1): 1–48. Publisher Full Text\n\nBoersma P, Weenink D: Praat: Doing phonetics by computer (6.4.03) [Computer software].2024. Reference Source\n\nChang CB: Phonetic drift.Schmid MS, Köpke B, editors. The Oxford handbook of language attrition. Oxford University Press; 2019; pp. 191–203.\n\nChristensen RHB: ordinal—regression models for ordinal data [Computer software].2023. Reference Source\n\nCook V: Effects of the second language on the first. Multilingual Matters; 2003.\n\nde Leeuw E : Phonetic attrition.Schmid MS, Köpke B, editors. The Oxford handbook of language attrition. Oxford University Press; 2019; pp. 204–217.\n\nde Leeuw E , Schmid MS, Mennen I: The effects of contact on native language pronunciation in an L2 migrant setting. Biling. Lang. Congn. 2010; 13(1): 33–40. Publisher Full Text\n\nFlege JE: Second language speech learning: Theory, findings, and problems.Strange W, editor. Speech perception and linguistic experience: Issues in cross-language research. York Press; 1995; pp. 233–277.\n\nFlege JE, Bohn O-S: The revised Speech Learning Model (SLM-r).Wayland R, editors. Second language speech learning: Theoretical and empirical progress. Cambridge University Press; 2021; pp. 3–83.\n\nFleiss JL, Cohen J: The equivalence of weighted kappa and the intraclass correlation coefficient as measures of reliability. Educ. Psychol. Meas. 1973; 33(3): 613–619. Publisher Full Text\n\nGuion SG: The vowel systems of Quichua-Spanish bilinguals: Age of acquisition effects on the mutual influence of the first and second languages. Phonetica. 2003; 60(2): 98–128. PubMed Abstract | Publisher Full Text\n\nInternational Phonetic Association: Handbook of the International Phonetic Association: A guide to use the International Phonetic Alphabet. Cambridge University Press; 1999.\n\nKarlsson F, van Doorn J : Vowel formant dispersion as a measure of articulation proficiency. J. Acoust. Soc. Am. 2012; 132(4): 2633–2641. PubMed Abstract | Publisher Full Text\n\nKartushina N, Frauenfelder UH: On the effects of L2 perception and of individual differences in L1 production on L2 pronunciation. Front. Psychol. 2014; 5: 1–17. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKartushina N, Frauenfelder UH, Golestani N: How and when does the second language influence the production of native speech sounds: A literature review. Lang. Learn. 2016; 66(S2): 155–186. Publisher Full Text\n\nKondo M, Pérez-Ramón R: Perception of Japanese accented English segments in words. J. Second Lang. Stud. 2023; 6(2): 210–237. Publisher Full Text\n\nKondo M, Tsubaki H, Sagisaka Y: Segmental variation of Japanese speakers’ English: Analysis of “the North Wind and the Sun” in AESOP corpus. J. Phon. Soc. Jpn. 2015; 19(1): 3–17. Publisher Full Text\n\nKonishi T: A corpus-based study on Japanese English rhythm. 2022. [Doctoral dissertation, Waseda University]. Reference Source\n\nKonishi T, Yazawa K: J-AESOP Rating Data (6_01 & 6_02). [Dataset]. Zenodo. 2024. Publisher Full Text\n\nKoo TK, Li MY: A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J. Chiropr. Med. 2016; 15(2): 155–163. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKornder L: Arnold Schwarzenegger now and then: A longitudinal case study of Schwarzenegger’s English and German pronunciation. Graz University Library Publishing; 2022.\n\nKuznetsova A, Brockhoff PB, Christensen RHB: lmerTest package: Tests in linear mixed effects models. J. Stat. Softw. 2017; 82(13): 1–26. Publisher Full Text\n\nLaméris TJ, Kubota M, Kupisch T, et al.: Language change in Japanese–English bilingual returnee children over the course of five years: Evidence from accent-rating. Second. Lang. Res. 2024. Publisher Full Text\n\nLee A, Kawahara T: Julius (4.5) [Computer software].2019. Reference Source\n\nLobanov BM: Classification of Russian vowels spoken by different speakers. J. Acoust. Soc. Am. 1971; 49(2B): 606–608. Publisher Full Text\n\nMayr R, Price S, Mennen I: First language attrition in the speech of Dutch-English bilinguals: The case of monozygotic twin sisters. Biling. Lang. Congn. 2012; 15: 687–700. Publisher Full Text\n\nMunro MJ, Derwing TM: Foreign accent, comprehensibility, and intelligibility in the speech of second language learners. Lang. Learn. 1995; 45(1): 73–97. Publisher Full Text\n\nR Core Team: R: A language and environment for statistical computing (4.4.1) [Computer software]. R Foundation for Statistical Computing; 2024. Reference Source\n\nSaito K, Trofimovich P, Isaacs T: Using listener judgments to investigate linguistic influences on L2 comprehensibility and accentedness: A validation and generalization study. Appl. Linguis. 2017; 38(4): 439–462. Publisher Full Text\n\nSanker C: How do headphone checks impact perception data? Lab. Phonol. 2023; 14(1): 1–45. Publisher Full Text\n\nSapir E: Language: An introduction to the study of speech. Harcourt, Brace and Company; 1921.\n\nTurner J: Phonetic development of an L2 vowel system and tandem drift in the L1: A residence abroad and L1 re-immersion study. Lang. Speech. 2023; 66(3): 756–785. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYazawa K, Konishi T, Whang J, et al.: Spectral and temporal implementation of Japanese speakers’ English vowel categories: A corpus-based study. Lab. Phonol. 2023a; 24(1): 1–33. Publisher Full Text\n\nYazawa K, Pérez-Ramón R, Kondo M: L2 proficiency predicts L1 accentedness and comprehensibility.Skarnitzl R, Volín J, editors. Proceedings of the 20th International Congress of Phonetic Sciences. Guarant International; 2023b; pp. 2840–2844. Reference Source\n\nYoung SJ, Kershaw D, Ollason D, et al.: The HTK Book Version 3.4. Cambridge University Press; 2006."
}
|
[
{
"id": "311386",
"date": "04 Sep 2024",
"name": "Takako Kawasaki",
"expertise": [
"Reviewer Expertise Phonology",
"SLA",
"Phonetics"
],
"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\nYazawa et al. (2024) investigate three key questions in the field of second language acquisition and first language attrition. First, they explore whether a foreign accent in the first language (L1) results from improvements in the second language (L2) or simply from reduced use of L1. Second, they examine whether the L1 foreign accent reflects changes in specific sound categories or a broader shift in the entire sound system. Lastly, they investigate how L2 learning impacts L1 comprehensibility.\nTo address these questions, Yazawa et al. analyzed a corpus containing speech samples from native Japanese speakers in both their native language (Japanese) and their second language (English). Japanese native speakers evaluated the foreign accent and comprehensibility of the L1 Japanese speech, while native English speakers assessed the nativeness of the L2 English speech. Additionally, the researchers conducted acoustic analyses of the Japanese and English vowels produced by each speaker.\nThe findings are intriguing. The study concludes that the L1 foreign accent is more likely to arise from reduced L1 use rather than L2 interference, suggesting that the foreign accent in L1 is more a result of language attrition due to decreased L1 usage, rather than an effect of improved L2 skills. Furthermore, they found that the accent changes in L1 pronunciation represent a shift at the system-wide level, rather than changes in specific sound categories.\nThe paper uses a methodical approach to these complex questions, employing appropriate methodologies. It provides a thorough review of previous research and offers insightful results and discussion. The authors also acknowledge the limitations of their study, particularly those related to the characteristics of the corpus, and suggest directions for future research.\nThis study contributes valuable insights to our understanding of how L2 learning can affect L1 pronunciation and comprehensibility. It challenges some common assumptions in the field, particularly with its finding that L1 foreign accent is more likely due to L1 attrition rather than L2 interference.\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": "320620",
"date": "19 Sep 2024",
"name": "Enrique Cámara-Arenas",
"expertise": [
"Reviewer Expertise Teaching of L2 English pronunciation"
],
"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 relevant and well-designed piece. It is concerned with determining elements that influence that backward acquisition of non-native features in L1 pronunciation possibly relatable to the attainment of L2 proficiency. Improving over existing literature on similar topics is the consideration of L1 comprehensibility. The conclusions are properly extracted and immediately relevant to the field. There is, as expected, an increase of L1 accentedness that corresponds to L2 proficiency, but seems causally related to a lack of use of the L1 for an extended period of time. The influence of the L2 over the L1 does not respond to a segment by segment projection of L2 units onto similar L1 units, but rather to a systemic economy apparently guided by the need to differentiate and separate L1 and L2 phonological repertoires. Interestingly, L1 comprehensibility appears to be enhanced with L2 proficiency. There are aspects of this research which I cannot fully judge, especially those concerned with the rigor of statistic treatment and procedure. The piece is, however, relevant, well written, convincing in its argumentation, and satisfactory in its conclusions.\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? No\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-867
|
https://f1000research.com/articles/13-719/v1
|
01 Jul 24
|
{
"type": "Research Article",
"title": "Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India",
"authors": [
"Tejaswi Pagadala",
"Gurudutt Kamath",
"Teena Mariet Mendonca",
"Gladys Rodrigues",
"Ajay Kamath",
"Tejaswi Pagadala",
"Gurudutt Kamath",
"Gladys Rodrigues",
"Ajay Kamath"
],
"abstract": "Objective Tuberculosis is a global health challenge with one-third of the world’s population infected by it. Although ocular side effects of Anti-tubercular drugs are well known, the patients generally report late in the course which can result in irreversible vision loss. The purpose of this study was to study the visual field changes during the time course of anti-tubercular therapy (ATT).\n\nMethods A total of 48 patients were studied in this prospective type of study. All patients newly diagnosed with TB and started on treatment were included in the study. Baseline examination which included visual acuity, color vision, anterior segment, IOP, Amsler grid, fundus, and visual field test were performed before starting ATT and at 6-month follow-up.\n\nResults The mean age of the study population was 35.90 ± 10.2 years. 35 (72.9%) were males and 13 (27.1%) females. 32(66.6%) had pulmonary TB and the rest 16 (33.3%) had extrapulmonary TB. MDR TB was diagnosed in 27 (56.3%) of the patients with the rest 21 (43.8%) being drug sensitive. The baseline examination was normal in all 48 patients. 3(6.3%) out of 45 patients presented with visual complaints after the treatment initiation. Altogether 7 patients out of 48, had visual field defects at the 6-month follow-up. The incidence of visual field defects in our study was 14.6% with the value being significant (0.016). 8.3% had peripheral constriction of visual fields, 2.1% with Severe generalized depression of visual fields and 2.1% with central scotoma. Out of the 45 patients with no visual complaints at 6-month follow-up, 4 (8.33%) showed peripheral field constriction.\n\nConclusion Visual field defects caused by ATT can precede clinical symptoms. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where Visual evoked potential testing and RNFL-OCT are not available.",
"keywords": [
"Mycobacterium tuberculosis",
"Drug toxicity",
"DOTS",
"visual field defects",
"toxic optic neuropathy",
"Ethambutol",
"Linezolid"
],
"content": "Introduction\n\nTuberculosis (TB) is one of the ancient diseases known to mankind that has co-evolved with humans for many decades1 and is a global health challenge.2 Among the world’s population, one-third are infected by it, and that makes TB, a public health concern.2–4 TB is one of the top three infectious killing diseases in the world1 and is also the leading cause of death from a single infectious agent.2 According to the India TB Report 2022, there is a 19% increase in cases (new and relapse) in 2021 from 2020.5 Interrupting its transmission is central to achieving the reduction in its incidence required to meet the End TB targets.5\n\nDOT (Directly observed therapy) is widely accepted and followed in many other countries and is the most effective.3 It is the fastest expanding and most extensive growing strategy and the second largest based on people initiated on treatment and population coverage, respectively.1 The standard treatment plan for tuberculosis usually is six months however, for resistant cases, it may even extend to 2 years with less potent and less toxic drugs1with treatment change based on the drug resistance.\n\nThe first line of drugs includes ethambutol, isoniazid, pyrazinamide, and rifampicin, and these are part of DOTS (Directly Observed Treatment Short course). Despite the increased availability of medical treatment, new challenges have developed with the growing incidences of drug-resistant tuberculosis that include DR-TB (drug-resistant), MDR-TB (multidrug-resistant), and XDR-TB (extensively drug-resistant).6\n\nATT-associated ocular toxicity was first established in the 1960s.7 Ethambutol and linezolid are the most common anti-TB drugs responsible for ocular side effects.4,8 Rare cases of Isoniazid-induced toxic optic neuropathy have also been reported.9,10 The toxic neuropathies associated with Ethambutol and linezolid account for about 1% and normally occur after 4-6 months of treatment.11 Optic nerve head and retinal nerve fiber layer changes are minimal in the early stages.7 The most common visual field defects associated with ethambutol and linezolid are central and centro-caecal scotomas,12 whereas bitemporal hemianopic scotomas with isoniazid.9\n\nTimely detection of ATT-induced optic neuropathy is essential since sight-threatening complications can be reversed if the drug causing the toxicity is discontinued at the earliest. The purpose of this study was to evaluate visual function in patients receiving ATT and to evaluate the visual field changes caused due to ATT.\n\n\nMethods\n\nThis was a prospective observational study done in a tertiary health care center, in south India, conducted from December 2020 to October 2022. The study was approved by the Institutional Ethics Committee (Kasturba Medical College, Mangalore affiliated to Manipal Academy of Higher Education, Manipal, India Approval No: IEC KMC MLR 12-2020/441) and abided by the tenets of the Helsinki Protocol. Patients above 15 years of age, newly diagnosed with TB who were started on anti-tubercular therapy were included in the study. A written informed consent was taken from all the patients. Patients who were previously on Anti Tubercular Therapy, patients with a previous history of the retina and optic nerve pathologies, and those with previously documented visual field defects were excluded.\n\nThe following tests were done at baseline (beginning of ATT) and at 6 months from the date of starting ATT. Baseline ocular examination which included best corrected visual acuity using Snellen chart and Jaeger chart, color vision using Ishihara plates, Slit amp examination, IOP with Goldman Applanation Tonometer, Amsler grid, Dilated fundus examination using slit lamp biomicroscopy and indirect ophthalmoscopy, and Humphrey visual field analysis 30-2 were done. Patients were advised to continue with their ATT and to review immediately in case of any visual symptoms. At the onset of visual symptoms, the drug responsible was identified and stopped.\n\nThe data was analyzed using IBM SPSS version 25. The nominal variables-type of color vision and fields at baseline and follow-up were compared using the Mc Nemer test for nominal variables; whereas the visual acuity was compared at baseline and follow-up using the Wilcoxon sign rank test for ordinal variables. A p-value of <0.05 was considered significant for all analyses.\n\n\nResults\n\nA total of 48 patients were part of this study. The mean age of the study population was 35.90 years ± 10.2 years. Among the 48 patients, 4 (8.3%) were 15-20 years of age, 13 (27%) in the age group of 21-30 years, and 8 (16.6%) in the age group of 31-40. Rest 23 (47.9%) patients are in the age group of 41-50 years.35 (72.9%) out of 48 were male and 13 (27.1%) were female.\n\nOf the total 48 patients included, 32(66.6%) patients had a diagnosis of pulmonary tuberculosis. Out of the 15 patients with extrapulmonary tuberculosis 4(8.3%) had disseminated tuberculosis, 4(8.3%) with TB lymphadenitis, 6(12.5%) with pleural effusion, 1(2.1%) with abdominal tuberculosis and 1(2.1%) with pott’s spine (Figure 1).\n\nTB REGIMEN: MDR tuberculosis, mainly rifampicin-resistant tuberculosis was found in 27(56.3%) at the time of their diagnosis and the rest 21 (43.8%) were drug-sensitive.\n\nOf the 27 with drug resistance, 2(4.2%) were initiated on a shorter bedaquiline regimen and 3(6.3%) on all oral longer MDR TB regimens (Table 1).\n\nVisual acuity at baseline for all the 48 patients included in the study was 6/6. 3(6.3%) out of 45 patients presented with visual complaints after the treatment initiation. 1 patient (2.1%) had vision of 6/18 with the other two patients (4.2%) below 6/60 (Table 2).\n\nColor vision examination was normal in all 48 patients during baseline evaluation. 3(6.3%) developed color vision abnormalities at follow-up with all of them being red-green deficient (Table 3). P value was 0.250 which is not significant.\n\nAnterior segment examination findings and IOP were normal in all patients at baseline and follow-up. Fundus examination was found to be within normal limits in all 48 patients at baseline. However, 3(6.3%) had abnormal findings at follow-up. 1(2.1%) had bilateral temporal disc pallor with the other two patients (4.2%) having bilateral hyperaemic disc (Figure 2).\n\nVisual fields at baseline for all 48 patients were normal. Out of the 45 patients with no visual complaints at 6-month follow-up, 4 (8.33%) showed peripheral field constriction. Out of the 8.33%, Constriction in one quadrant was observed in 2.1% whereas constriction in 2 quadrants was observed in 6.3%. 3(6.3%) patients developed visual symptoms during the treatment course, out of them, peripheral field constriction was noted in one patient (2.1%), one showed severe generalized depression of visual fields (2.1%) and the other patient had central scotoma (2.1%). p-value of 0.16 was calculated which was found to be significant (Table 4).\n\nAll three of these patients with visual complaints were on linezolid as part of their all-oral long bedaquiline regimen. The three patients with visual symptoms were immediately advised to stop the linezolid and even the TB center had been notified of the same.\n\nTo confirm the diagnosis in the three patients with visual symptoms VEP and RNFL OCT was done which showed prolonged P100 latency and thinning of the RNFL layer.\n\nThe visual acuity, color vision, and visual field defects improved in two of the three patients within 1-2 months with the average being 1.5 months post-stopping linezolid. Visual symptoms of one patient however did not improve even after stopping linezolid which can be attributed to a longer duration of drug intake.\n\n\nDiscussion\n\nBaseline visual acuity was normal in all patients, however, 3 (6.3%) patients complained of visual symptoms with 2 reported vision less than 6/60. This is similar to Garg et a13 at 8.69%, Ashraf et al,14 at 10.6%, Panchal et al,4 7.44%, and Goyal et al,15 at 3.3% incidence of visual complaints. However, no patient in studies done by Saxena et al,16 Menon et al,17 Kandel et al,18 Kim et al,19 Jin et al,8 had any visual complaints.\n\nColor vision abnormality was noted in 6.3% of our patients similar to 5.32% as seen in a study done by Panchal et al.4 All our patients had Red-Green deficiency in contrast to the study by Ashraf et al,14 who had 23.23% of people with color vision abnormalities with the maximum being blue-yellow deficient.\n\nOut of 48 people in our study on fundus examination, 4.2% had disc edema and 2.1% had temporal disc pallor. The findings in these patients were bilateral. Similar findings were noted by Panchal et al4 who had 2.12% with bilateral disc edema and 2.12% with bilateral disc pallor. A study done by Ambika et al,20 showed 44.14% with disc pallor and <1% showed disc edema.\n\nThe incidence of visual field defects in our study was 14.6% with the value being significant (0.016). 2.1% had a peripheral constriction in all 4 quadrants, 2.1% with Severe generalized depression of visual fields, and 2.1% with central scotoma. In our study, 4 patients (8.3%) showed Peripheral field constriction in different quadrants making it the most common field defect similar to the study done by Ashraf et al,14 in which 13.3% had field defects with 8.15% being peripheral field defects in different quadrants. However, visual field defects in patients receiving anti-tubercular therapy varied in different studies. Bitemporal field defects were observed by Kho et al12 in his study, centro-caecal scotomas (2.12%) were observed by Panchal et al.4 Garg et al13 in their study concluded that 8.69% (8 eyes of 4 patients) with visual field defects with centro-caecal scotoma in one patient and the rest with peripheral constriction. Few studies like Kandel et al,18 Kim et al,19 Jin et al,8Saxena et al,16 observed no visual field changes in any of their patients on anti-tubercular therapy. The limitations of this study include that reaching a definite conclusion by extrapolation of results to the general population was not possible due to the small sample size. the patients were not followed up at shorter intervals, the accurate time of onset of the side effects could not be studied. Incidence of visual field defects was 14.6% in our study with 6.25% of them reporting visual symptoms.\n\nVisual field defects caused by ATT can precede clinical symptoms. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where visual evoked potential testing and RNFL-OCT are not available. Patients on ATT should be regularly screened for ocular adverse effects preferably every month. Routine examinations like visual acuity, color vision, and fundus examination must be carried out to look for any subclinical effects of the treatment and monitor their progression.\n\nChest physicians, ophthalmologists, and Health care workers need to be aware of potentially sight-threatening side effects of ATT. Prompt diagnosis and timely intervention are the keys to optimal visual outcomes in patients with toxic optic neuropathy due to ATT.\n\n\nDeclarations\n\nInstitutional Ethical committee clearance for the study was obtained.",
"appendix": "Data availability\n\nOpen Science Framework: Visual field changes in patients receiving antitubercular therapy, https://doi.org/10.17605/OSF.IO/SAQMC. 21\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nNone\n\n\nReferences\n\nSandhu GK: Tuberculosis: Current situation, challenges, and overview of its control programs in India. J. Global Infect. Dis. 2011; 3: 143–150. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGupta V, Testi I, Agrawal R, et al.: Ocular tuberculosis: Where are we today? Indian J. Ophthalmol. 2020; 68: 1808–1817. PubMed Abstract | Publisher Full Text | Free Full Text\n\nImam F, Sharma M, Khayyam KU, et al.: Adverse drug reaction prevalence and mechanisms of action of first-line anti-tubercular drugs. Saudi Pharm. J. 2020; 28: 316–324. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPanchal K, Solu TM: Ocular side effects of anti-tubercular drugs in patients receiving Anti-Tb treatment at Tertiary Care Center. Int. J. Ocul. Oncol. Oculoplasty. 2020; 6: 187–191. Publisher Full Text\n\nMinistry of Health & Family Welfare-Government of India. Home: Central TB Division; [Accessed 16 Nov 2022]. Reference Source\n\nPezzella AT: History of pulmonary tuberculosis. Thorac. Surg. Clin. 2019; 29: 1–17. Publisher Full Text\n\nKim YK, Hwang JM: Serial retinal nerve fiber layer changes in patients with toxic optic neuropathy associated with antituberculosis pharmacotherapy. J. Ocul. Pharmacol. Ther. 2009; 25: 531–536. PubMed Abstract | Publisher Full Text\n\nJin KW, Lee JY, Rhiu S, et al.: Longitudinal evaluation of visual function and structure for detection of subclinical ethambutol-induced optic neuropathy. PLoS One. 2019; 14(4): e0215297. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSharma R, Sharma P: Toxic optic neuropathy. Indian J. Ophthalmol. 2011; 59: 137–141. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOmmurugan B, Bhattacharjee D, Patil N: Isoniazid the culprit behind toxic optic neuropathy. Asian J. Pharm. Clin. Res. 2017; 10: 1. Publisher Full Text\n\nLibershteyn Y: Ethambutol/linezolid toxic optic neuropathy. Optom. Vis. Sci. 2016; 93: 211–217. PubMed Abstract | Publisher Full Text\n\nKho RC, Al-Obailan M, Arnold AC: Bitemporal visual field defects in ethambutol-induced optic neuropathy. J. Neuroophthalmol. 2011; 31: 121–126. PubMed Abstract | Publisher Full Text\n\nGarg P, Garg R, Prasad R, et al.: A prospective study of ocular toxicity in patients receiving ethambutol as a part of directly observed treatment strategy therapy. Lung India. 2015; 32: 16–19. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMahrukh AA, Bhat MA: Visual field changes in patients receiving antitubercular drug therapy at tertiary care hospital: an analytical observational study. Int. J. Contemp. Med. Res. 2017; 4: 346–349.\n\nGoyal JL, Sarmi D, Singh NP, et al.: Evaluation of visual functions in patients on ethambutol therapy for tuberculosis: a prospective study. J. Commun. Dis. 2003; 35: 230–243. PubMed Abstract\n\nMandal S, Saxena R, Dhiman R, et al.: Prospective study to evaluate incidence and indicators for early detection of ethambutol toxicity. Br. J. Ophthalmol. 2020; 105: 1024–1028.\n\nMenon V, Jain D, Saxena R, et al.: Prospective evaluation of visual function for early detection of ethambutol toxicity. Br. J. Ophthalmol. 2009; 93: 1251–1254. PubMed Abstract | Publisher Full Text\n\nKandel H, Adhikari P, Shrestha GS, et al.: Visual function in patients on Ethambutol therapy for tuberculosis. J. Ocul. Pharmacol. Ther. 2012; 28: 174–178. Publisher Full Text\n\nKim KL, Park SP: Visual function test for early detection of ethambutol induced ocular toxicity at the subclinical level. Cutan. Ocul. Toxicol. 2015; 35: 228–232.\n\nAmbika S, Kp L, Gopal M, et al.: Visual outcomes of toxic optic neuropathy secondary to Ethambutol: A retrospective observational study from India, an endemic country. Indian J. Ophthalmol. 2022; 70: 3388.\n\nMendonca TM, et al.: Visual field changes in patients receiving antitubercular therapy. [Datatset]. Open Science Framework. 2024. Publisher Full Text"
}
|
[
{
"id": "298163",
"date": "12 Jul 2024",
"name": "Karthik Vinay Mahesh",
"expertise": [
"Reviewer Expertise Areas of intrest is Neurology. Neuro-ophthalmology and neuroinfections"
],
"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 look into an important field of drug induced optic neuropathy in patients of tuberculosis, which is a public health concern. However, there are several shortcomings in the methodology 1.) The most important factor is the offending drug, Ethambutol being the most common needs special mention regarding its dosage / Kg body weight and duration of intake before visual symptoms 2) The incidence of visual field defects should be treated as signs of optic neuropathy not just decrease in visual acuity as its based on central field of vision which is the last to go. 3)The other important comorbidities like diabetes/ old age/ renal dysfunction/ Vit- B12 deficiency and tb arachnoiditis with optic neuropathy should be ruled out 4) the inclusion criteria of the study is not mentioned, the study has very high no. of patients taking MDR regimen/ Bedaquiline. which is very high for the population. 5) The citations are incorrect. \" TB affects 1/3rd of world population \" source has been mentioned by an article on Ocular TB by V Gupta et al. The references need to substantiate the content which the authors are quoting. 6) The study needs major revisions with manuscript writing 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? 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": [
{
"c_id": "12066",
"date": "01 Aug 2024",
"name": "Teena Mariet Mendonca",
"role": "Author Response",
"response": "Reviewer Comment: The authors look into an important field of drug-induced optic neuropathy in patients of tuberculosis, which is a public health concern. 1.) The most important factor is the offending drug, Ethambutol being the most common needs special mention regarding its dosage / Kg body weight and duration of intake before visual symptoms Author Response: The average dosage of ethambutol received by the patients in our study was 20mg/kg body weight for 6 months. However, all oral longer MDR TB regimen patients received Linezolid 600 mg for 6 months. Since all the patients were assessed at 6 months, the duration of drug intake in the study cohort was 6 months. 45 out of 48 patients had no visual symptoms during treatment. 3 patients presented with blurred vision at the end of 6 months. Reviewer Comment: 2) The incidence of visual field defects should be treated as signs of optic neuropathy not just decrease in visual acuity as its based on central field of vision which is the last to go. Author Response: We agree with the reviewer. The message we want to convey to the reader is subclinical visual field defects could be the first sign of impending optic neuropathy in patients receiving ATT. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where visual evoked potential testing and RNFL-OCT are not available. Reviewer Comment: 3)The other important comorbidities like diabetes/ old age/ renal dysfunction/ Vit- B12 deficiency and tb arachnoiditis with optic neuropathy should be ruled out Author Response: We have excluded patients under the age of 15 and above 50 years of age. All the conditions causing retinal pathology/optic neuropathy such as diabetics, patients with renal dysfunction, those with previously documented visual field defects, patients with nutrional optic neuropathy including vitamin B12 deficiency and patients with TB arachnoiditis and patients with previously treated TB. The suggested changes have been made in the article. Reviewer Comment: 4) the inclusion criteria of the study is not mentioned, the study has very high no. of patients taking MDR regimen/ Bedaquiline. which is very high for the population. Author Response: Inclusion criteria has been mentioned in the article. Our center is district TB center which is a nodal center for TB control and referral center for drug resistant TB. Hence probably the the number of MDR cases are high. Reviewer Comment: 5) The citations are incorrect. \" TB affects 1/3rd of world population \" source has been mentioned by an article on Ocular TB by V Gupta et al. The references need to substantiate the content which the authors are quoting. Author Response: As per the reviewer’s suggestion I have made correction in the text as well as the reference. Reviewer Comment: 6) The study needs major revisions with manuscript writing methodology. Author Response: Our best attempt to revise the manuscript has been made"
}
]
}
] | 1
|
https://f1000research.com/articles/13-719
|
https://f1000research.com/articles/13-865/v1
|
01 Aug 24
|
{
"type": "Research Article",
"title": "Approaches towards pragmatic language assessment in Indian pre-schoolers: A survey among speech-language pathologists",
"authors": [
"Saniya Rasheeka",
"Sudhin Karuppali",
"Jayashree Bhat",
"Megha Mohan",
"Aiswarya Varghese",
"Saniya Rasheeka",
"Jayashree Bhat",
"Aiswarya Varghese"
],
"abstract": "Background Pragmatic language assessment in children is performed in line with standard protocols, guidelines, and best practices. The absence of these aspects in the Indian context has resulted in the quest to explore the approaches used by speech-language pathologists (SLPs) to assess pragmatic language impairments. This survey explored the current practices of SLPs towards the assessment of pragmatic language among preschool children in India. It also aimed to identify the barriers, facilitators and identify the level of knowledge, skill and overall practice of SLPs towards their practices using self-appraisal.\n\nMethods A total of 100 SLPs(94 females and 6 males) working with preschool aged children (three-to-six-year-olds) from across different Indian states participated in the survey. Participants were enquired about the aspects of pragmatic language assessed, methods used for assessment, awareness and use of Indian tools, the settings, members, and language used for the assessment. Additionally, they were asked to mention the specific tools used, informal methods used, barriers and facilitators, and self-appraise their knowledge, skill and overall practice.\n\nResults Majority of participants assessed multiple aspects of pragmatic language. All used a combination of different assessment methods, with the participants commonly using informal compared to formal approaches. Preschoolers were assessed at multiple settings, along with different communication partners. Lack of awareness on assessment tools developed in India was the major barrier, while the use of informal tasks or activities were the major facilitators influencing pragmatic language assessment to a greater extent. The knowledge and skills for the assessment of pragmatic language obtained poorer scores compared to practices.\n\nConclusions The assessment practices of the SLPs were largely influenced by the unavailability of developed or adapted tools for Indian preschoolers, leading to the need to develop indigenous assessment tools. Certain considerations for further assessment practices have been identified and discussed.",
"keywords": [
"assessment",
"barriers",
"facilitators",
"pragmatic language",
"preschoolers",
"self-appraisal",
"speech-language pathologists",
"survey"
],
"content": "Introduction\n\nPragmatic language, often referred to as ‘pragmatics’ is the ability to apply language resources to facilitate effective social interaction, considering the needs of the conversational partner and demands of the physical context (Stephens & Matthews, 2014). It encompasses the unspoken rules and ways of making communication appropriate and effective within specific contexts. This primarily includes the understanding and using of language for different purposes, such as to comment, direct, reject, protest, greet, inform, demand, state, promise, request, etc. Secondly it comprises of changing language according to the listener needs (considering partner’s age and relationship) such as (a) talking appropriately to unfamiliar individuals, (b) shifting registers, using stylistic variations according to the age of the communication partner, (c) using polite forms such as ‘please’ during requests especially when the communication partner is older or less familiar and in a dominant role, (d) being extra polite when demanded, and(e) using indirect requests. It also includes changing language according to situations, using a different tone or altering the choice of words in the classroom when compared to the playground. Lastly, pragmatics includes following the rules of the conversation such as, initiating a conversation with a question/statement, introducing new topics, maintaining the topic, taking turns, seeking for clarification, repairing a communication breakdown, clarifying, and organizing the structure for different discourse genres like narration and expository (Cummings, 2014; Matthews et al., 2018).\n\nPragmatic competence requires the sophisticated coordination between linguistic (Vogindroukas et al., 2021), social (Šimleša & Cepanec, 2015), and cognitive skills (Papafragou, 2018; Toe et al., 2020). Owing to the parallel development of these skills, pragmatic language is acquired early in childhood, playing a pivotal role through preschool years (3 to 6 years) (Fahey et al., 2019). The emergence and refinement of social communication skills during this period (Alduais et al., 2022), lays a foundation for building relationships as children begin to form bondswith peers, neighbours, teachers, and others apart from the immediate family (Dillon et al., 2021). With preschool entry, children acquire basics of classroom behaviour such as greeting, listening, asking questions, following group instructions, thereby preparing to navigate themselves through academic-social environments. They begin to assert independence, express likes and dislikes through self-exploration and expression, thus developing a sense of identity and autonomy. These children identify, express, and manage emotions thereby effectively communicating feelings, asking for help, or offering comfort to others, thereby acquiring knowledge about the world through social interactions. Everyday conversations provide ample opportunities for expanding vocabulary, understanding complex concepts, and building existing knowledge (Clark, 2018). Pragmatic skills such as negotiating in order to settle disagreements among peers, problem-solving skills to resolve social challenges become a part of a preschooler’s life. In essence, the development of pragmatic language helps preschoolers navigate the social world, build relationships, and lay the groundwork for future academic and social success (Toe et al., 2020).\n\nA delay or impairment in the pragmatic language during childhood results in long-term negative impact on the child’s personal, academic, social and various other aspects of life (Dillon et al., 2021; Elleseff, 2015; Loukusa et al., 2018). Reports of a growing trend in neuro developmental disorders have resulted in an increase of language impairments encountered by speech-language pathologists (SLPs) all over the world (American Speech-Language-Hearing Association, 2022). A high prevalence of language impairments among Indian children have been reported (Konadath et al., 2013, 2017; Shanbal et al., 2015; Sinha et al., 2017), that isinclusive of certain disorders explicitly diagnosed based on pragmatic language characteristics (Swineford et al., 2014). Pragmatics forms the central feature in identifying Autism Spectrum Disorders (ASD) (Hage et al., 2022; Wong et al., 2022). An increase in the prevalence rates (89 per 10,000) of ASD in India (Poovathinal et al., 2016) has raised concerns among SLPs (Dillon et al., 2021). Given that the majority of children are not diagnosed with ASD until or after the age of 4 or 5 years (Centers for Disease Control and Prevention, 2019), or median age of 4.5 years (Brett et al., 2016), SLPs are more likely to encounter preschool age children with ASD symptoms whose diagnosis are awaited (Binns et al., 2022). Furthermore, fifth edition of Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) included a definite diagnostic criteria for social (pragmatic) communication disorder as an independent addition characterized exclusively on pragmatic abilities. This has further exemplified the need to identify impairments related to pragmatic language among children by using suitable assessment measures (Salari et al., 2022). However, the understanding of developmental norms (Gerber et al., 2012; Izaryk et al., 2021; O’Neill, 2014) including the clinical methodologies and intervention approaches (Ash et al., 2017; O’Neill, 2014; Swineford et al., 2014) are still in its infancy.\n\nGlobally, there exists best practices in the assessment and intervention of various neurodevelopmental disorders resulting in pragmatic deficits (Adams et al., 2015; Elleseff, 2015; Timler, 2018). However, in India, there has been an inadequate amount of information guiding SLPs towards the same, despite the increase in the prevalence of pragmatic language impairments and the need for early identification and timely intervention. The absence of standard protocols, guidelines, and/or best pragmatic language assessment tools does result in inconsistencies among practicing SLPs, leading to the poor identification of impairments, and the lack of confidence in one’s own practice. In the face of such challenges, it becomes important to understand the approaches used by SLPs to identify and assess pragmatic language impairments in children. Therefore, the first and foremost initiative is to explore the current practices (Binns et al., 2022) based on the nature of pragmatic assessment (‘what is being assessed in pragmatics?’, ‘how has it been assessed?’, ‘where to assess?’, ‘what tools and materials are available or can be used?’, and many more). Such questions require collective responses to find the most prevalent and benefitting practices that can be consequently imbibed during the assessment of pragmatics among preschoolers. Therefore, the primary aim of the current study was to explore the current SLP practices towards the assessment of pragmatic language among Indian preschoolers using a survey method. Most survey studies lack the SLPs’ perspectives towards the barriers and facilitators to optimal service delivery, as well as their self-assessment of knowledge, skills, and overall practice. It therefore becomes critical to understand clinicians’ perspectives to ensure the development of assessment and/or interventions enabling optimal service delivery (Binns et al., 2022). Self-appraisal forms a fundamental skill required throughout learning and constant self-performance evaluation in an SLP’s career (Yan, 2020). Therefore, the current study also aims to identify the barriers and facilitators towards the assessment of pragmatic language among preschoolers and identify the level of knowledge, skill and overall practice of SLPs towards their own assessment routines.\n\n\nMethods\n\nA cross-sectional online survey design was adopted for the present study as it aimed to obtain an understanding of the assessment practices among SLPs across the country. The study was approved by the Institutional Ethics Committee of Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, India as a part of a doctoral study (IEC KMC MLR 12-2020/418) on 18-03-2021. Informed consent was obtained from the participants by voluntarily placing a tick (✓) on the checkbox prior to participation in the study since the survey was conducted online using Google Forms.\n\nThe questionnaire was developed by the authors to survey SLPs’ current approaches towards assessment of pragmatic language among preschoolers in India. Section one of the questionnaire involved demographics, work setting, and caseload details of the participant (SLP), while section two involved forced-choice questions on pragmatic language assessment practices in preschoolers. Section three targeted the barriers and facilitators in pragmatic language assessments and its influence on the same (Damschroder et al., 2022), using a four-point Likert rating scale [1–barrier/facilitator to no extent (alternatively meaning, not a barrier/facilitator), 2–barrier/facilitator to a little extent, 3–barrier/facilitator to a moderate extent, 4–barrier/facilitator to a great extent] (Kajermo et al., 2010). Section four targeted the participant’s knowledge, skill, and overall practice in pragmatic language assessments using a five-point Likert rating scale of quality (1–poor, 2–below average, 3–average, 4–good, 5 – excellent). The presence of various question types such as filling in the blank statements, rating scales, forced-choice, multiple-response, and open-ended questions were deemed to capture the comprehensive practices followed by the participants (Binns et al., 2022). Considering the limitation of using forced-choice and multiple-response question types (Gillon et al., 2017), aprovision of reporting any other type of descriptive responses beyond the choices presented in the questionnaire was also included (Binns et al., 2022; Izaryk et al., 2021). Lastly, the questionnaire concluded with an opportunity for the participants to provide any additional remark pertaining to their practices.\n\nThe initial version of the questionnaire was subjected to content validation by five SLPs on a five-point Likert rating scale for item relevance (from 1 being irrelevant to 5 being highly relevant) (Polit & Beck, 2006). Additionally, feedback and comments were sought for each item in the questionnaire. The Content Validation Index (CVI) for the overall item level CVI scores ranged between 0.9-1.00 and scale-level CVI scores for each section was 1.00, both indicating excellent content validity (Polit et al., 2007). Feedback from the content validation was integrated, and the final questionnaire (Rasheeka et al., 2024) was ready to be piloted among six SLPs to determine the item clarity, logical sequence of questions, and the response options across the questionnaire.\n\nPotential participants received the survey information sheet with the link to the online questionnaire via one of two modes: (a) posting a research participation request on the Indian Speech-Language and Hearing Association (ISHA) website (www.ishaindia.org.in), and (b) posting research requests on professional groups and social networking platforms such as WhatsApp and Instagram. A snowball sampling method was followed to aid wider distribution of the survey to potential participants. The online link to the survey was open for 60 days (from 1st August to 30th September 2023), and the responses were collected through Google Forms (a web-based platform). Multiple participation from the same participant was prevented by turning on the ‘limit to 1 response’ option on Google Forms. A total of 100 (94 females and six males) SLPs registered under the Rehabilitation Council of India (RCI) participated in the survey. The participants worked with preschool aged children (3 to 6 years) at various settings within India in the last six months. The respondents were from Karnataka (n=52), Kerala (n=21), Tamil Nadu (n=14), Maharashtra, Gujarat, Rajasthan (n=2in each), Pondicherry, Delhi, Haryana, West Bengal, Assam, Bihar, and Telangana (n=1in each). The participants took 15 minutes on average to complete the survey. Table 1 shows the demographic details of the current study participants.\n\nThe responses were subjected to quantitative and qualitative analysis based on the type of survey question. Descriptive statistics was employed using Jamovi version 2.4.8. For questions with multiple item responses or with a large number of responses, the options were grouped into overarching categories (Lal et al., 2022). For open-ended questions (such as the use of different formal assessment tools, informal tasks or activities, and materials), the responses were analysed using content analysis and grouped into main categories (Braun & Clarke, 2006). As it was not mandatory to respond to all open-ended questions, the data was reported as a percentage of the number of responses received (indicated by denominator). Subgroup analysis and data triangulation across questions was used to elucidate further information (Lal et al., 2022). The qualitative analysis of the obtained responses regarding the assessment practices were important in corresponding with the obtained quantitative data (Gillon et al., 2017).\n\n\nResults\n\nThe survey results provided a comprehensive overview of SLPs’ pragmatic language assessment practices, approaches, barriers, facilitators and self-appraisal in terms of knowledge, skills, and overall practice.\n\n\n\ni. Caseload representation and choice of pragmatic language assessment\n\nMost of the SLPs’ case load included a greater percentage of preschoolers with ASD, Delayed Language Development (DLD) (collective term used for children with primary difficulties in language), and Attention Deficit Hyperactivity Disorder (ADHD). The assessment of pragmatic language among these language disorders have been reported to be at a higher rate when compared to preschoolers with diagnoses such as Global Developmental Delay (GDD), Intellectual Disability (ID), Down's syndrome (DS), Cerebral Palsy (CP), Cleft Lip and Palate (CLP), or any other. The caseload representation and proportion of each diagnosison whom pragmatic language assessment was conducted by the study participants are presented in Table 2.\n\nFifty-three percent of the participants reported performing a routine assessment of pragmatic language on every preschool aged child in their caseload, of which 64.15% (34/53) performed screening, 24.53% (13/53) performed screening and diagnostic assessment, and 11.32% (6/53) performed a diagnostic assessment. Forty-seven percent of the participants assessed for pragmatic language on a part of their caseload, of which 78.72% (37/47) performed only screening, 14.89% (7/47) performed screening and diagnostic assessment, and6.38% (3/47) performed a diagnostic assessment.\n\nii. Assessment of different aspects of pragmatic language\n\nAll study participants assessed multiple aspects of a preschooler’s pragmatic language. Forty-three percent of the participants assessed all the five aspects of pragmatic language (see Table 3). Twenty-two percent of the participants assessed a combination of three aspects, preschooler’s way of using language for different purposes (greeting, thanking, informing, requesting, etc.), conversation and narrative abilities. Additionally, the ‘other’ option category received responses such as identifying play behaviours, language used during play, awareness of body proximity, intention to communicate, participation in social interaction, expression of emotions and desires, interpretation of humour, theory of mind and child’s personality. While all these additional responses targeted on profiling the child’s pragmatic language abilities, one of the responses emphasized on identifying the parent’s role and their interaction style during a conversation with the preschooler.\n\niii. Methods to assess pragmatic language\n\nInformal tasks or activities were used by majority (92%) of the participants, followed by parent-child interaction (90%) and other methods (see Figure 1). Most participants (98%) used a combination of different assessment methods except for two of them who used only informal tasks or activities during an interaction with preschoolers. The most frequent number of methods combined by the participants was 5 (M = 4.74, SD = 1.43, range: 1-8) and the commonly reported (15%) combination of assessment methods included, peer-child interaction, observation of child in natural settings, parent or caregiver report or interview, parent-child interaction, and informal tasks or activities during the interaction with preschoolers. The next most reported (12%) combination included the same methods except for peer-child interaction.\n\nParticipants were further enquired about the different tasks or activities used as a part of informal approach, and the different tools used as a part of formal or standardized approach to assessment. As the probe questions were optional, the results were based on the number of responding participants.\n\na. Use of informal tasks and activities: The various informal tasks and activities reportedby34 participants were broadly classified into six categories. Different kinds of play were mentioned repeatedly by most SLPs (n = 34). Figure 2 provides a visual representation of the frequency of categories and subcategories of the tasks and activities used for the assessment of pragmatic language among preschoolers.\n\nFurthermore, participants were enquired about the different materials (or objects) used during the assessment. The various materials mentioned by 38 SLPs were broadly classified into five categories. Toys were reported more frequently (54), followed by books (14) and other materials. Figure 3 provides a visual representation of the different materials reported of being used by the survey participants for the assessment of pragmatic language among preschoolers.\n\nb. Use of assessment tools: Twenty-seven participants explicitly mentioned the standardized tools used for the assessment of pragmatic language among preschoolers (see Table 4). Out of which, 23 distinct assessment tools were identified which included those specifically designed for pragmatic language (10), comprehensive language (9), and other unidentifiable tools (4). It was reported that participants did not necessarily administer the entire tool for the assessment of pragmatic language (mentioned in the table), rather used relevant sections from certain available tools. The use of pragmatics profile section from Clinical Evaluation of Language Fundamentals (CELF) - 4th and 5th edition was reported by most (7) of the SLPs, followed by Speech and Language Development Chart (SLDC) (4), Pragmatics Profile of Everyday Communication Skills in Children (PPECS) (4) and other tools. In addition to the reported tools, one of the participants stated utilizing sections of DSM-5 for the assessment of pragmatic language.\n\nc. Awareness on Indian tools for pragmatic language assessment for preschoolers: Among the total100 participants, only a few (16%) reported of being aware of and having access to Indian developed assessment tools, of which six of them listed Communication DEALL Developmental Checklist (CDDC), Checklist for Assessment of Pragmatics in Preschoolers (CAPP), Preschool Language Scales – 5th edition (PLS) (Zimmerman et al., 2011), Test of Pragmatic Language – 2nd edition (TOPL) and two other unidentifiable assessment tools (Test of Early Milestones and PLI). Of the mentioned tools, only two (CDDC, CAPP) were developed for Indian population. Twenty-three participants reported of being aware, but having no access to Indian developed assessment tools, of which four listed CDDC and two used tools (Pragmatic assessment test and Pragmatic assessment tool) that were unidentifiable for the purpose of the study. Nevertheless, there was a significant number of participants (61%)who were unaware of any Indian developed tools for the assessment on pragmatic language for preschoolers.\n\niv. Setting for the pragmatic language assessment for preschoolers: Majority of the SLPs reported of performing an assessment of pragmatic language at multiple settings, with 42% of them assessing at the testing/consultation room, child’s home, and preschool environment;47% assessing at the testing/consultation room, and preschool environment; and56% assessing at testing/consultation room, and the child’s home environment. On the other hand, participants assessed in single settings [at home (2%), and their testing/consultation room (34%)]. While few participants reported of using videos of the child in different environment, others reported otherwise. For e.g., one of the participants mentioned “I don’t actually go personally to child’s home or school and assess; rather, I obtain information from different environments using parent interview or report”. One of the participants reported of conducting assessment in children’s play area.\n\nv. Members involved in the pragmatic language assessment for preschoolers: During the assessment of pragmatic language among preschoolers, involvement was reported from parent/s and/or caregiver/s (98%), siblings (70%), co-clinicians (57%), peers (49%), and teachers (38%). Twenty-two percent of the SLPs reported involving all the five members during the assessment in their practice, while two participants also mentioned including family members and other professionals working with the child. One of the participants stated, “though the presence of peers and teachers are very important, it is often not feasible to work with them”.\n\nvi. Language used for pragmatic language assessment for preschoolers: In terms of the language used for the assessment of pragmatic language, a majority (82%) of the SLPs reported assessing the same in the preschooler’s native language, 48% assessed in all languages the child was fluent in, while22% assessed in the language which was deemed as the medium of instruction at their school.\n\nvii. Source of normative data on pragmatic language of preschoolers: For the normative data on the development of pragmatic language among Indian preschoolers, SLPs relied on scholarly research articles (65%), discussion with colleagues (61%), their own experience and judgment (59%), books on child language development (57%), and internet (blogs, webpages, social media) (33%). Most participants (86%) used more than one source to obtain the normative data on pragmatic language. Five percent of the SLPs reported using all the five sources to obtain information on pragmatic language development among Indian preschoolers.\n\nThe barriers and its influence on the assessment of pragmatic language in preschoolers was rated on a four-point Likert rating scale. The barriers and the extent of its influence (average mean) on the assessment routine were the lack of awareness on assessment tools developed in the Indian context (3.2), the lack of assessment tools at work setting (3.02), the lack of research in the area of pragmatic language in India (2.92), the presence of associated behaviours (e.g., hyperactivity, inattention) (2.87), the lack of knowledge related to development and assessment of pragmatic language (2.59), the lack of time available for assessment (2.48), and the lack of experience assessing pragmatic language on preschoolers (2.48). The barriers and its influence on the assessment of pragmatic language is graphically presented in Figure 4.Other barriers perceived to limit the participants from effectively conducting an assessment of pragmatic language among preschoolers were stated as, “incomplete profiling of the child’s pragmatic language due to non-feasibility of assessing in multiple settings such as child’s home, school, and situations such as peer group etc.”, “biased parental reporting and poor reliability of the information provided by parents”, “lack of access to resources specific to the pragmatic language development among Indian children”, “lack of importance given to pragmatics as a part of language in general, during the graduate teaching or even during later clinical practice”, and, “there are many other areas to be assessed so assessing each in detail would be difficult”.\n\nThe list of facilitators and its influence on the assessment of pragmatic language was rated on a four-point Likert rating scale. The facilitators and the extent of its influence (average mean) on the assessment routine were the use of informal methods to assess pragmatic language (3.61), the opportunity to observe the preschooler interact with multiple conversation partners (parent, peer, SLP) (3.51), the increased exposure to children with language impairments (3.41), the involvement of parents, teachers, peers in the assessment (3.38), the increasing years of clinical experience (3.33), the revised DSM-5 criteria for diagnosis (e.g., Social Communication Disorder) (3.15), and the opportunity to observe the preschooler in different settings such as at clinic, home, school (3.02). The facilitators along with its influence on the assessment of pragmatic language is graphically presented in Figure 5. Other facilitators stated by the SLPs included having discussion with colleagues pertaining to the same and having more interaction time with the child.\n\nSLPs’ knowledge, skill, and overall practice towards assessment of pragmatic language among preschoolers were identified on a five-point Likert rating scale of quality, where 1 = poor, 2 = below average, 3 = average, 4 = good, and 5 = excellent. Knowledge of SLPs about the development of pragmatic language among preschoolers obtained higher mean (3.37) when compared to knowledge of available assessment methods (3.01) which in fact was observed to have obtained the least mean score across any item on the self-appraisal section. The skills of SLPs to identify pragmatic impairment/deficits among preschoolers obtained higher mean (3.66) when compared to the skills to perform assessment of pragmatic language on preschoolers (3.46). In terms of self-appraising SLPs practices, the practice of SLPs to perform assessment of pragmatic language among preschoolers obtained a higher mean (3.48) when compared to the overall practice towards the assessment of pragmatic language among preschoolers(3.41). Overall, the results indicate knowledge domain to be significantly poorer compared to the skills and overall practice domains; and in specific, the knowledge, skill and practices related to assessment of pragmatic language was poorer. The meanand percentage of participants’ rating for each item of self-appraisal is represented in Table 5.\n\n\nDiscussion\n\nThe study aimed to explore SLP practices towards the assessment of pragmatic language among Indian preschoolers, the barriers, facilitators, and self-appraisal of knowledge, skills, and overall practices. Using a survey method, the study gathered information from 100 SLPs working with preschool children across 13 states of India, providing a comprehensive understanding of the prevalent assessment practices. The main findings on the approaches, barriers, facilitators, and self-appraisals based on the assessment of pragmatic language of preschoolers are discussed below.\n\nCaseload representation and choice of pragmatic language assessment\n\nPreschoolers with ASD were encountered by a majority (95) of SLPs in the study. These findings are consistent with studies reported from India (Mendonsa & Tiwari, 2018), United States of America (American Speech-Language-Hearing Association, 2022; Izaryk et al., 2021), Canada (Binns et al., 2022), and other countries globally (Gillon et al., 2017). With the increase in global prevalence rates of ASD (Zeidan et al., 2022), early age of identification (Brett et al., 2016; Centers for Disease Control and Prevention, 2019), and intervention (Gillon et al., 2017), it becomes foreseeable for preschoolers with ASD to be encountered more frequently by SLPs (Binns et al., 2022) as evident in the findings of this study. While 73.68% (70/95) of SLPs assessed for pragmatic language on this population, 26.32% (25/95) failed to do so. Since ASD is primarily characterised by social communication and pragmatic language deficits (Swineford et al., 2014), an assessment of pragmatic language becomes crucial. On similar lines, preschoolers with DLD being commonly reported in India (Binu et al., 2014; Sidhu et al., 2013), have been encountered by the SLPs (with an equivalent majority as ASD). This indicates ASD and DLD to be the two most prevalent diagnoses in the caseloads of SLPs working with preschool age children in India. In terms of assessment, 69.47% (66/95) of SLPs evaluated pragmatic language among preschoolers with DLD, while 30.53% (29/95) failed to do so. Although not primarily a social or pragmatic language disorder, assessing pragmatic language becomes crucial due to strong evidence of pragmatic language deficits among preschoolers with DLD (Vassiliu et al., 2023; Wong et al., 2022). Concurrently, preschoolers with a diagnosis of ADHD were encountered by 85 SLPs. Among them, 71.76% (61/85) assessed for pragmatic language, except for the 28.24% (24/85). ADHD being characterised with poor topic maintenance, incoherent narration and other pragmatic language deficits (Carruthers et al., 2022; Norbury et al., 2014; Norbury & Bishop, 2003), it becomes important to assess the same. In comparison with other neurodevelopmental disorders (GDD, DS, CP, CLP and others) (on whom SLPs assessed pragmatic language in less than 50% of the total number encountered), the SLPs conducted pragmatic language assessment on a relatively larger percentage [59.38% (38/64)] of preschoolers with ID. Overall, it was found that SLPs prioritized the assessment of pragmatic language on preschoolers diagnosed with ASD, DLD and ADHD. This preference may stem from ASD’s recognition as a social communication disorder, the association of ADHD with pragmatic language impairments, and the relatively higher prevalence of DLD within SLPs caseloads. Over half of the participants (53%) reported conducting routine assessments of pragmatic language on every preschooler in their caseload, while 47% assessed only a proportion of them. Majority (71%) of the SLPs preferred only screening as opposed to conducting diagnostic or in-depth evaluation, possibly due to unavailability or the absence of specific diagnostic tools for Indian preschoolers.\n\nAssessment of different aspects of pragmatic language\n\nIn the current study, most SLPs assessed multiple aspects of pragmatic language such as the way of using language for different purposes, conversation abilities, narrative abilities, the way of adapting language according to listener (considering partner’s age and relationship) and situation, while one-third of the participants assessed all these aspects. It is encouraging to note that all SLPs from the study reported of assessing multiple aspects of pragmatic language among preschoolers. This comprehensive approach is crucial since pragmatic language skills are foundational for effective communication and social interaction (Dillon et al., 2021; Green et al., 2014; Toe et al., 2020). It was observed that the aspect related to the way of adapting language according to listener and situation were comparatively less assessed by SLPs. This could be attributed to the limited availability of communication partners of varying ages and roles, as well as the challenge of replicating situations in a testing environment respectively. Regardless of the clinical diagnosis, each aspect of a preschooler’s pragmatic language should be assessed (Gillon et al., 2017). By ensuring multiple aspects of pragmatic language to be assessed, SLPs obtain a comprehensive profile of the child’s abilities, providing more effective and individualized support, ultimately enhancing the child's overall communication abilities (Adams, 2002; Norbury & Bishop, 2003).\n\nMethods to assess pragmatic language\n\nUsing appropriate approaches to assess pragmatic language among children is crucial (Wong et al., 2022). While each method has its own strengths and weaknesses, the most ideal approach remains questionable. Professional guidelines suggest incorporating standardized tools as an integral part of the diagnostic process (Betz et al., 2013). However, the dynamic nature of pragmatic language necessitates evaluation across different individuals, situations and environments reflective of natural everyday life (Denman et al., 2023), a requirement that standardized tools are unable to meet. Reasonably, only 38% of the participants have reported of using standardized tools for the assessment of pragmatic language, concurrent with best practices that warn the cautious use of formal assessment tools for several reasons (Brinton & Fujiki, 2019; Izaryk et al., 2021; Norbury et al., 2014; O’Neill, 2014; Timler, 2018). Firstly, due to its inability to capture the dynamic and context-dependent nature of social communication or pragmatics; and secondly, due to the lack of ecological validity and difficulty in terms of standardizing. Furthermore, anecdotal evidence based on clinical reports suggest a mismatch between children's pragmatic knowledge and their ability to apply the same in real-life situations thus recommending clinical evaluations to incorporate in-person assessments (Carruthers et al., 2022).\n\nTraditionally, natural observation methods were most preferred, providing an understanding of pragmatic language skills as used by children in real-life situations (Wong et al., 2022). This preference has evidently continued as majority of the participants reported of using natural observations (80%), parent-child interactions (90%), and peer-child interactions (55%). Researchers in India commonly use these methods at child’s home, school or test environment to study the development of pragmatic language (Harinath & Raghunathan, 2017; Shilpashri & Chengappa, 2015; Shilpashri & Shyamala, 2020). In clinical practice, majority (64%) of the SLPs reported assessing preschoolers’ pragmatic language in more than one environment, however, 36% assessed only in a single environment. Most of them assessed pragmatic language of preschoolers at the test/consultation room compared to other settings such as home, preschool, etc. Though assessing in multiple settings is recommended (Binns et al., 2022; Tulviste & Schults, 2023), the constraints of increasing caseloads and lack of resources, makes it challenging for SLPs to visit different environments of preschoolers and conduct observations in-person. Alternatively, SLPs have begun requesting video recordings of preschoolers in these environments. In the present study, three SLPs reported requesting such recordings.\n\nIn the absence of the provision to visit in-person or obtain video recordings of preschoolers in different environments, information about the child can be gained from parents, caregivers, and teachers through interviews, checklists or questionnaires. Having a number of individuals of different age and relation during the assessment of pragmatic language provides a scope to assess for specific aspects of pragmatic language such as the way of adapting language to different listeners and also situations (Manohar et al., 2024). However, these methods are prone to recall bias, positive praise, and manipulation of information (Krupa et al., 2019). According to studies conducted in Canada, United States of America and United Kingdom, parents desire to be a part of the evaluation so as to communicate, collaborate, be informed, share knowledge, and be able to build a positive relationship with their child (Gillon et al., 2017; Starr & Foy, 2012). In this study, majority of the SLPs used methods that require gathering information from parents and caregivers (81%) than teachers (25%), possibly due to the lack of questionnaires developed in India for teachers, difficulty in reaching out to them (as also reported by one of the participants in the study), convenience (parents or caregivers typically accompany their children for consultation) and economy of time (Krupa et al., 2019). Although parents tend to have a broad, detailed, and naturalistic view of their child’s pragmatic language skills, having teachers’ systematic observations of the child in preschool environment through reports and/or interviews provide a holistic perspective towards pragmatic language assessment (Tulviste & Schults, 2023). Additionally, involving siblings and peers can offer valuable insights into the nuances of pragmatic language within similar age group (Tulviste & Schults, 2023). While this may be feasible in certain clinical settings, it may not be possible in others.\n\nUse of informal methods for the assessment of pragmatic language are often reported as time consuming and challenging to apply in clinical contexts (Toe et al., 2020). Despite the drawback, the data from this survey revealed majority (92%) of the SLPs to have used informal tasks and activities to assess pragmatic language among preschoolers (Binns et al., 2022; Izaryk et al., 2021). Further to corroborate the findings, it was observed that time was not regarded as a major factor for the assessment of pragmatic language among preschoolers. On the contrary, the use of informal means of assessment was reported as a facilitator to a greater extent by majority of the participants (66%). Furthermore, from the open-ended responses to the survey, the scope of using informal tasks and activities seemed potent, with a participant stating “there are a lot of informal tasks and activities to even mention” and another mentioning, “there is no one particular activity; any activity depending on the child's interest can be used”.\n\nTypically, informal tasks or activities are staged situations that mimic a naturalistic context, where the SLP and child involves in real-life social interactions. This enables the SLP to create multiple opportunities and observe the child’s pragmatic language competency in a naturally created social context rather than solely relying on information from others. Informal methods have incorporated stories (Anil et al., 2021; Loukusa et al., 2018), conversations (Wetherell et al., 2007), narrations (personal narratives, story narrations) and other tasks or activities into structured or unstructured interactions during the assessment of pragmatic language. Using such tasks allows researchers and SLPs to observe and assess language in an ecological way, as used by the child in everyday situations (Wetherell et al., 2007). The potential of using informal tasks and activities to provide insight into the preschoolers pragmatic language in action highlights the future assessment opportunities for SLPs in the absence of culturally developed standardized tools, and constraints of assessing the child in multiple contexts (Izaryk et al., 2021).\n\nIt is important that the materials used during the assessment of pragmatic language among preschoolers are age-appropriate, age-relevant, versatile and can provide scope to elicit different pragmatic language skills (Manohar et al., 2024). It becomes equally important to use materials that gain child’s interest, attention, and participation (Ferjencik, 2019). From the results of the study, toys were reported to be the most frequently used material. Beyond their common availability at a SLPs’ clinic for engagement and reinforcement purposes, toys are highly useful for creating numerous contexts to assess various pragmatic language skills thus making it most suitable during the assessment of pragmatic language among preschoolers (Ferjencik, 2019). Other specific toys reported and found to be used in studies include pictures, small characters, plastic animals (Loukusa et al., 2018), blocks, phones, puppets (Shulman, 1986), utensils, cars, balls, bubbles, papers, crayons, books, boxes, eatables and others (Ferjencik, 2019; Zimmerman et al., 2011). Additionally, two participants reported using videos during the assessment of pragmatics in the preschoolers. Although the specific purpose whether to capture and present the child's language use in situations beyond those directly observed by the SLP, or to display animated or recorded social situations to assess child's pragmatic language competency (Lavi et al., 2016) remains unknown; nonetheless, the potential of using videos in the assessment of pragmatic language is increasing.\n\nAwareness and use of assessment tools for pragmatic language assessment\n\nMajority (61%) of the SLPs reported of being unaware of Indian developed tools for the assessment on pragmatic language in preschoolers. Recently there have been no Indian tools developed specifically to assess pragmatic language of preschool age children. The developed tools in the past included the Developmental Protocol for Pragmatics (Dheepa & Shyamala, 2005), and Test of Pragmatics (Sundaram & Karanth, 1994) [an adaptation of Test of Pragmatic Skills (Shulman, 1986)]. Both these tools remain unpublished, confined to the institutional archives making it inaccessible to SLPs, and are now considered obsolete.\n\nIn terms of using tools for the pragmatic language assessment, majority of the participants reported western-standardized tools, with CELF being most commonly used by SLPs in the current study and also globally (Betz et al., 2013; Gillon et al., 2017; Izaryk et al., 2021). Nonetheless, SLPs in India commonly used un-adapted versions of the western tools on preschoolers for the assessment of pragmatic language due to the unavailability and inaccessibility to indigenous tools. Though these tools have been standardized and proven efficient in identifying deficits in pragmatic language, they remain inapplicable in the Indian context due to the cultural and linguistic influence unless adapted otherwise. The only Indian developed tools reported to be used by the participants of the current study were the CDDC, LPT, Indian Scale for Assessment of Autism (ISAA), and CAPP. CDDC is a criterion referenced checklist (administered on children from birth to six years), that assesses developmental skills on eight domains of which one being social skills. LPT involves the assessment of phonology, syntax, and semantics with a small part of discourse (Suchitra & Karanth, 1989). Although reported to be used by one of the participants in this study, this tool (LPT) does not involve the assessment of pragmatic language per se nor assess preschool age children (Mendhakar & Priyadarshi, 2018). ISAA is an objective assessment tool (administered on children of 3 years and above until 22 years) that uses a 5-point rating scale to identify deficits on six domains of which one included social relationship and reciprocity. A recent study by Manohar et al. (2024), revealed ISAA to be unable to accurately capture the profile of children having good expressive language abilities but lacking social-communication skills due to pragmatic language impairment. Further, the tool has demonstrated suboptimal performance among children <5 years of age. CAPP is a modification to an earlier adaptation of the preschool version of PPECS to Marathi speaking children in India. This tool uses a parental or caregiver checklist to obtain information on four sections: interaction and conversation, communicative functions, contextual variation and response to communication on Marathi speaking children between birth and 4 years, excluding children between 5 and 6 years of age. It becomes important to consider the publication year of tools for assessment, as tools published over 15 years ago (except for CAPP) may not be suitable for use, as their stimulus items might no longer be socially relevant or commonly encountered (Betz et al., 2013; Salvia et al., 2017).\n\nThe Indian developed tools reported by participants in the study were either western developed (CELF, SLDC, PLS) or adapted versions (CAPP), comprehensive language test with a minor portion on pragmatics or social communication (CDDC), unsuitable to the age of the child [Linguistic Profile Test (LPT)] or specifically developed for children with ASD focusing on social relationship and reciprocity, and not pragmatic language abilities (ISAA). It was alarming to observe SLPs report of western tools (PLS, TOPL) when specifically enquired about Indian developed tools indicating the lack of knowledge and awareness about pragmatic tools and its targeted audience.\n\nWith over 19 assessment tools listed by the current study participants, the findings reinforce the critical need for the development of indigenous tools to identify pragmatic language impairments among preschoolers, as also iterated by Binns et al. (2022). In developing countries such as India where SLPs manage with limited resources, locally adapted tools requires to be developed and accessible (Chakraborty et al., 2015). Tools particularly targeting the assessment of pragmatics in India are less, compared to the other aspects of language (Landa, 2005), as also evidenced by participants in the current study. Given the limited focus on the assessment of pragmatic skills in India, there is a dire need to develop culturally sensitive pragmatic assessment tools (Anil et al., 2021). As stated “tools need not be extensive but should be comprehensive to provide sufficient opportunities for children to express their abilities” (Krupa et al., 2019).\n\nLanguage used for the assessment of pragmatic language\n\nSince bilingualism and multilingualism are a common aspect in India, conducting direct assessments on one-to-one basis raises questions on the language used to assess the child. An evaluation in both the languages is highly recommended when considering children from a bilingual background (Patla et al., 2023; Tulviste & Schults, 2023). With the first language being the child’s native language, the second language will often be a locally spoken language, or the language used as a medium of instruction at the preschool. The results of the study revealed majority of the SLPs to have used the preschooler’s native language for the assessment, while 32% assessed pragmatic language in both (native and medium of instruction at preschool). The effective implementation of this practice is limited to the wide variety of languages spoken across India, the odds of finding SLPs or translators proficient in those languages, and the unavailability of tools (Valliappan et al., 2022). As a contingency measure, questionnaires and checklists should include items that assess the pragmatic aspect regardless of the language spoken by the child (Pesco & O’Neill, 2023).\n\nSources of normative data on pragmatic language\n\nThe United States ranked the highest, followed by the United Kingdom and China, in producing research on pragmatic language development (Alduais et al., 2022). As a result, it is possible that the clinical practices in India are largely an adaptation of Western approaches. Given India's cultural and linguistic diversity, it is essential to develop indigenous theoretical and practical frameworks for the development, assessment, and intervention of pragmatic language. However, despite the limited resources with respect to the development and assessment of pragmatic language among Indian preschoolers (Patla et al., 2023), there is evidence that SLPs frequently engage in research-informed practices. Most participants referred to research articles, books and collaborated with colleagues. Although around 59% of the SLPs relied on their own experience and judgment (though being an important aspect in the clinical decision-making), 33% reported using information platforms such as the webpages, blogs and social media to educate on the same.\n\nSLPs being professionals actively involved in the identification and provision of intervention among children with various neurodevelopmental disorders, it becomes essential for them to be updated with the developments in the field (Mendonsa & Tiwari, 2018). Disseminating information on newly published research articles, assessment tools, methods, interventions or advances related to pragmatic language through creative means such as posts, posters, flyers, and other printables on social media, social networks (professional groups), and other platforms becomes the need of the hour.\n\nThe barriers largely influencing the assessment included the lack of awareness on assessment tools developed in the Indian context. Though it is encouraging to observe SLPs considering their unawareness as a barrier, there have not been any Indian tools recently developed pragmatic language assessment, with the exception of CAPP (Deosthalee & Waknis, 2020). Other barriers similarly influencing the assessment included the lack of assessment tools at work setting, and lack of research in pragmatic language in India. Considering the reports from the SLPs of the current study, it has become evident that these barriers have influenced the assessment practices resulting in them using the available tools irrespective of the cultural or language background of the child (Valliappan et al., 2022). This could potentially lead to over-estimating the extent of impairments due to the variation between the Western and Indian English.\n\nSome of the facilitators influencing the assessment to a greater extent included, the use of informal methods to assess pragmatic language, opportunity to observe preschoolers interact with different conversation partners (parent, peer, SLP), increased exposure to children with language impairments, and the involvement of parents, teachers, peers in the assessment. Although the use of informal approaches are often considered time-consuming (Toe et al., 2020), time was considered to only minimally influence the SLPs of the current study. However, it is important to consider prolonged assessments to fatigue the preschoolers influencing their performance (Betz et al., 2013). Hence it becomes important that a set of informal tasks or activities are pre-set and employed in an engaging manner with the preschooler. Involving multiple communication partners and providing an opportunity to interact with each of them provides a holistic outlook of the preschooler’s pragmatic language. Having an increased exposure with preschoolers of different diagnoses leads to experiential learning for SLPs, thereby influencing their decision-making abilities.\n\nSLPs self-appraised their knowledge on the methods for pragmatic language assessment as being poorer compared to the developmental patterns of pragmatic language among preschoolers. Similarly, the skills to assess pragmatic language was felt to be poorer compared to the skills to identify pragmatic impairments among preschoolers. The SLPs collectively obtained poorer scores on items related to the assessment of pragmatic language, attributing it to the absence of guidelines and best practice recommendations for pragmatic language assessment for Indian SLPs. Overall, the knowledge aspects obtained poor scores compared to skill and practice. SLPs can identify their strengths and weaknesses, and adjust their learning and practices accordingly through self-appraisal of own performances (Yan, 2020). It becomes important for SLPs to become educated on the development of culturally and linguistically appropriate assessment tools, different methods, relevant and recent research work, during their education and profession. SLPs require to be constantly updated through newsletters, broadcasts, e-mails, scientific seminars, webinars, conferences, etc. Only when SLPs are aware of available tools would they procure and use the same for clinical practice.\n\nThe findings from the current study provide valuable insights on SLPs’ approaches to pragmatic language assessment of preschoolers in the absence of best practices or clinical guidelines in India. The prevalent SLP practices included the preference for screening over in-depth evaluations, assessment of multiple aspects of pragmatic language, using multiple methods (with majority using informal tasks and a small number using standardized tools including both western and Indian), inclusion of parents/caregivers to gain additional information about the child, use of preschooler’s native language to conduct assessment and mostly at the test room setting. SLPs will now be able to identify the extent to which their practices align or differ from the clinical practices of peer SLPs within the country. The result of the current study provides a greater understanding of the most prevalent and benefitting practices thereby directing SLPs towards effective pragmatic language assessment of preschoolers in India. Perspectives towards the barriers, facilitators, knowledge, skills and practices of SLPs are beneficial to clinicians, academicians and researchers in the field.\n\nThe study findings are limited to a small number of participants relative to the number of SLPs working with preschoolers in India. Although the survey link was posted on the ISHA website, a major number of SLPs participated from Karnataka, possibly due to the abundance of speech and hearing institutions in the state. In this regard, further surveys may consider using measures to obtain equal participation from SLPs across India. The present study attempted to minimize the possibility of recall bias by enquiring information based on the assessment practices over the past six months as opposed to longer intervals. However, as inherent to this type of data collection (survey), the information provided could not be verified.\n\nPragmatic language assessment among preschoolers using in-person observations require supplementing information from other evaluation methods (questionnaires, interviews or reports). Consistent with recommended practices for assessment (Izaryk et al., 2021; Tager-Flusberg et al., 2009; Timler, 2018), the SLPs of the current study reported using multiple methods during the assessment process (Binns et al., 2022). In the event of a discrepancy in the preschooler’s pragmatic language abilities observed with the information reported, the need for assessment data to be collected from multiple informants becomes crucial (Sturrock et al., 2020). Gaining information from individuals (parents, caregivers, teachers, peers) with whom the preschooler spends significant time is utmost essential (Farmer & Oliver, 2005; Tulviste & Schults, 2023; Wong et al., 2022). A sensible strategy would be to combine measures of pragmatic language from more than one source (Charman, 2004). A multi-informant approach becomes valuable helping mitigate factors that may impact objectivity (Manohar et al., 2024). The best practice to obtain a holistic pragmatic language profile of preschooler, should include the evaluation of the different aspects, using multiple methods inclusive of informal tasks and activities, involving members of the family and others significant communication partners to the child, and obtain information from multiple settings tailored to the preschooler (Elleseff, 2015; Izaryk et al., 2021; Krupa et al., 2019). Using a range of assessment tools, inclusive of formal and informal measures derived from multiple sources and across different contexts, is important to enhance the validity of assessment results (Binns et al., 2022; Tager-Flusberg et al., 2009). Ultimately, the results of this survey recommend SLPs to undertake a comprehensive approach to the pragmatic language assessment of preschoolers (Gillon et al., 2017).\n\n\nEthics\n\nThe study was approved by the Institutional Ethics Committee of Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, India as a part of a doctoral study (IEC KMC MLR 12-2020/418) on 18-03-2021.\n\n\nConsent\n\nInformed consent was obtained from the participants by voluntarily placing a tick (✓) on the checkbox prior to participation in the study since the survey was conducted online using Google Forms.",
"appendix": "Data Availability\n\nOpen Science Framework: Data sheet for ‘Approaches towards pragmatic language assessment in Indian pre-schoolers: A survey among speech-language pathologists’.\n\nhttps://doi.org/10.17605/OSF.IO/V4Q2Z\n\n(Rasheeka et al., 2024)\n\nThis project contains the following underlying data:\n\n• Data sheet.xlsx (Participant demographics and responses to each section of the survey on separate sheets of a single Excel workbook)\n\n• Checklist for Reporting of Survey Studies (CROSS).docx (Completed checklist)\n\nOpen Science Framework:Survey questions for ‘Approaches towards pragmatic language assessment in Indian pre-schoolers: A survey among speech-language pathologists’.\n\nhttps://doi.org/10.17605/OSF.IO/V4Q2Z\n\n(Rasheeka et al., 2024)\n\nThis project contains the following extended data:\n\n• Survey questionnaire.docx (Survey questions in a word document)\n\nData areavailable for access on Open Science Framework under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 Public Domain Dedication).\n\n\nAcknowledgements\n\nThe authors would like to thank all the speech-language pathologists who have participated in this survey and acknowledge the support of Indian Speech-Language and Hearing Association by posting our research participation request on their website.\n\n\nReferences\n\nAdams C: Practitioner review: The assessment of language pragmatics. 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}
|
[
{
"id": "310418",
"date": "07 Aug 2024",
"name": "Ahmed Alduais",
"expertise": [
"Reviewer Expertise Clinical Linguistics",
"Developmental Psychology",
"Mixed Methods 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\nDear Colleagues,\n\nThanks for sharing your paper about pragmatic language assessment in Indian preschoolers. I have enjoyed reading your paper which seems to be a well-conducted piece of research.\n\nThe introduction covers all the basic and needed topics related to the examined areas with recent and classic studies in the field. However, I suggest the authors conclude their introduction with stating the study aims or questions.\n\nThe methods seem to be average but could be upgraded by applying some minor changes. I suggest using the typical headings including sample, design, measures (validity and reliability of the used measures) and procedure (data collection, data analysis and ethical considerations).\n\nThe results section is excellent, so I have no comment on this section.\n\nThe same applied to the discussion and the rest of the manuscript.\n\nI do wish you all the best in applying these minor revisions.\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?\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": "322026",
"date": "26 Sep 2024",
"name": "Pallavi Kelkar",
"expertise": [
"Reviewer Expertise Speech and language development",
"early detection of language delays",
"fluency disorders",
"professional voice"
],
"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 thank the researchers and the journal for the opportunity to review this work. Overall, I think this paper is a necessary addition to literature in order to get a better perspective on the way assessment of pragmatics is conducted by speech-language pathologists in India. Barring a few additions that the method and discussion sections might require, I think that the paper is well-written. The objectives, results and conclusions are well-aligned with each other. The structure of the survey instrument reveals that the researchers exhaustively covered different aspects of assessment of pragmatics including barriers, facilitators and self-appraisal of the participants’ knowledge and skills. I have put down my comments and suggestions for specific sections of the paper below.\nI recommend using the phrase \"assessment of pragmatics\" in the title as well as throughout the paper. Although the researchers establish in the introduction itself that, ‘pragmatic language’ and ‘pragmatics’ both mean the same thing, use of the term \"pragmatic language\" might be misinterpreted as restricted to ‘language assessment’. \"Pragmatics\" could better reflect the inclusion of communication, non-verbals, etc. especially for a reader who might not be very familiar with these terminologies, considering the wide readership of this journal. The abstract aptly conveys the essence of the study. The Introduction covers an extensive review of existing literature and makes a case for the present study. However, some of the phrases in the introduction might benefit from rewording after a general spelling and grammatical check. For example, “the listener’s” and not “the listener needs” on line 5 of the Introduction; a space missing between “is inclusive” in paragraph 3, line 5; “Globally there exist best practices…” and not “exists”, and similar minor edits. Similarly, some phrases, albeit conveying the right content, could be clearer to readers if reworded. For instance, page 4 line 11, “…required throughout learning and constant self-evaluation in an SLP..”. Rewording this as \".... required first during training to be an SLP and later, for evaluation of one's own performance as a professional\" could make it clearer to the reader. A similar example is the last line of the Introduction that reads, “Therefore, the current study also aims to identify the barriers and facilitators towards the assessment of pragmatic language among pre-schoolers and identify the level of knowledge, skill and overall practice of SLPs towards their own assessment routines.” This does not connect well with the previous sentence, which talks about self-evaluation of knowledge and skills by SLPs. Along these lines, the Introduction as well as the rest of the document could benefit from an overall spelling and grammar check once over. Other than these minor suggestions, the Introduction does justice to the topic chosen for study, in my opinion.\nI had a few queries with reference to the Method section. Firstly, the sample largely comprised of SLPs from Karnataka. Although the researchers did acknowledge that as a limitation of the study, I would be interested to know if there were any particular challenges they faced in getting a sample more representative of different states in India. This would have added considerably to the study’s applicability across India.\nIn the first line of the sub-section titled Survey questionnaire, the researchers state, “The questionnaire was developed… to survey SLP’s current approaches towards …assessment of pragmatic language…”. This description of the questionnaire does not do justice to the multiple areas it covers. I recommend rewording this description to better reflect the nature of the questionnaire and align with the aims of the study.\nThe first line of the second paragraph under the same subheading mentions that the judges were five SLPs. It would be useful to know how many years of experience they had, and whether any of them had experience specific to construction and conduction of surveys. The last sentence of the same paragraph mentions, “…the final questionnaire was ready to be piloted among six SLPs to determine the item clarity, logical sequence of questions, and the response options across the questionnaire.” It would be great if there was a short paragraph that followed, sharing the results of this pilot.\nLine 3 of the subheading Data analysis mentions that for open ended questions, the responses were grouped into main categories. Was this grouping done independently by two or more researchers? During classification into categories was there 100 percent agreement between researchers? If not, how was this resolved? Mentioning these details could benefit replication of the survey in future.\nLastly, in the questionnaire, under the section on self-appraisal by SLPs, I was not clear about the difference between “Practice to perform assessment of pragmatic language among pre-schoolers” and “Overall practice towards the assessment of pragmatic language among pre-schoolers” within the domain, Practice. Clarification of this difference could help readers interpret the results better.\nThe results have been appropriately presented and the tables and graph convey all the necessary information. I would like to appreciate the researchers for their excellent choice of graphs for all of the results presented in the document. Using the right kind of graphs makes the findings very clear, even to a reader who might not have in-depth knowledge of the topic. In the discussion, the researchers make a good attempt at explaining the results and corroborating them with literature. However, an additional facet to the discussion could be to corroborate findings of different sections of the questionnaire within the study itself. In the last line under the section Approaches to pragmatic language assessment, they mention that most SLPs preferred screening, “probably due to unavailability of diagnostic assessment tools”. Since they have data to support this point (dearth of published assessment instruments from India as apparent from the literature review and reference list, lack of assessment tools reported by respondents in the section on Barriers), that can be mentioned here as well. Other barriers such as lack of time, etc. that surfaced in the survey could also be discussed as possible reasons for preferring screening over assessment.\nOn page 14, under Awareness and use of assessment tools for pragmatic language assessment, in the last sentence of the third paragraph, the researchers express alarm over the SLPs having mentioned western tools when the question specifically enquired the use of Indian tools. Despite this, the SLPs’ self-appraisal scores for knowledge, skills and practices were 3 or more. Were the SLPs accurate in their self- appraisal? Also, what could have been the reasons for their incorrectly reporting names of tests (western as Indian)? Did their self-appraisal of their skills and practice reflect in their responses to other sections of the questionnaire? Corroborating findings across different sections of the questionnaire in this manner could make the discussion richer.\nAnother addition could be to discuss the responses obtained in the “Other” category under the subsection on assessment of different aspects of pragmatics. Some of the responses might reflect SLPs’ lack of perspective with regards to assessment of pragmatics. For instance, would “awareness of body proximity” be applicable to assessment of pre-schoolers? Similarly, would assessment of “a child’s personality” reflect a child’s understanding of pragmatics? A child might be an introvert but still communicate appropriately as the situation demands. These responses could be discussed in the discussion section, highlighting that lack of protocols and best practices might lead clinicians to assess aspects which might not come under the scope of pragmatic development of pre-schoolers.\nMinor additions and rephrasing in a few places could also benefit the discussion. Under the section on Barriers and facilitators to pragmatic language assessment, in the last sentence of the first paragraph the researchers mention that using Western instead of Indian tools could potentially lead to overestimation of the extent of impairment. I am not sure if it would always be a case of overestimation, because pragmatics is being assessed, and not syntax.“Inaccurate estimation” would be a better choice of phrase. Lastly, under the section titled “The way forward”, it would be great to have the researchers’ suggestions on what can be done to improve knowledge, skills and availability of resources for SLPs.\nI commend the authors on having taken a step towards streamlining the assessment process for diagnosis of pragmatic impairments among pre-schoolers. I hope this research inspires action taken for setting up assessment protocols and best practices for assessment of pragmatics by SLPs in India.\nRegards Pallavi Kelkar\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": "322030",
"date": "09 Oct 2024",
"name": "Leslie Kokotek",
"expertise": [
"Reviewer Expertise My areas of expertise include (but are not limited to): child speech-language development",
"communicative participation",
"functional communication",
"assessment psychometrics",
"multi-lingual/cultural research."
],
"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 is well written, clearly cited, and provides good rationale underscoring the need for this study. There are a few minor typos in the introduction that should be corrected prior to going to print.\n\nIn the results section I think DLD more commonly refers to Developmental Language Disorder. This is the term used by ASHA so it may not be applicable to this context. There are also some spacing issues when reporting percentages and other numbers.\n\nThe figures are nicely done and help to efficiently visualize the qualitative data.\n\nIdeally, I would like to see a slightly extended description on the content analysis and how the data were examined.\n\nThis statement right here \" This indicates ASD and DLD to be the two most prevalent diagnoses in the caseloads of SLPs working with preschool age children in India\" I think is too forward of a claim to make given that only 100 SLPs were surveyed. This claim needs to be scaled back.\n\nThe discussion is a bit dense and I think perhaps some of the information such as the information about recall bias for parents would be better suited in the introduction rather than the discussion section. However, this may be a personal preference and I think reasonable the manuscript could move forward with indexing either way.\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?\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
|
https://f1000research.com/articles/13-865
|
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